LATS Expediente1.indd

Transcrição

Está é uma publicação
Direção executiva e comercial
Silvio Araujo
André Araujo
Coordenação médica
Dra. Fernanda Chaves Mazza
(CRM-RJ 52.71.644-8)
Coordenação editorial
Roberta Monteiro
Ana Paula Aquino
Coordenação criação
Gabriel Meneses
Jornalismo
Gisleine Gregório
Luciene Cimatti
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LATS journal
Latin Amerin Thyroid Society
É um verdadeiro prazer para a Sociedade Latinoamericana de Tireoide apresentar o segundo número da
Revista LATS em formato eletrônico. Esta se configura
como instrumento da SLAT para a difusão internacional
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de Trabalho da SLAT, análises de artigos e comentários
de livros.
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Comitê Editorial
Guillermo Juvenal (Chair) – Argentina
José Luis Novelli – Argentina
José Higino Steck – Brasil
Derek Barragan – Bolívia
Denise Pires de Carvalho – Brasil
Maria Teresa Nunes – Brasil
María Montesinos – Argentina
Liliana Bergoglio – Argentina
Gisah Amaral de Carvalho – Brasil
Rosalinda Camargo – Brasil
Egberto Moura – Brasil
Eduardo Faure – Argentina
Feranando Munizaga – Chile
Claudio Liberman – Chile
Claudia Riedel – Chile
Ana Luiza Maia – Brasil
Claudia Pellizas – Argentina
Laura Ward – Brasil
Carmen Aceves – México
Jorge Jara Yorg – Paraguai
Fernando Luis Diaz – Brasil
Vergilius J A Furtado Filho – Brasil
Nelson Wohllk – Chile
Marcos Abalovich – Argentina
Alicia Gauna – Argentina
Comitê executivo
2013-2015
Presidente
Ana Maria Masini-Repiso, PhD – Córdoba,
Argentina
Presidente eleito
Denise P. Carvalho – Rio de Janeiro, Brasil
Secretário
Eduardo K. Tomimori - São Paulo, Brasil
Tesoureiro
Erivelto Martinho Volpi - São Paulo, Brasil
Diretores
Ana Luiza Maia – Brasil
Ana Maria Orlandi – Argentina
Carmen C. Pazos Moura - Brasil
Edna T. Kimura – Brasil
Gabriela Brenta – Argentina
Hans Graf – Brasil
Marcos S. Abalovich – Argentina
Marial de Mar Montesinos – Argentina
Tania M. Ortiga Carvalho – Brasil
Sumário
Sumário
Artigos
Bocios multinodulares mixtos tratados con 131I e inyecciones de etanol en forma combinada*............................................15
Jara Yorg JA, Jara MA, Jara Ruiz JM, Jara Ruiz ED
Comentarios sobre las recomendaciones de la guía: management of thyroid dysfunction during pregnancy and pospartum:
an endocrine society clinical practice guideline* Comparación con la guía de la endocrine society del año 2007...................22
Marcos Abalovich
Accidental occupational exposure to radiation induces thyroid nodules.................................................................................28
Mario A. Pisarev M.D.1; Marta Schnitman M.D.2; Guillermo J. Juvenal PhD1
Resumos
PO001 CORRELAÇÃO ENTRE CÂNCER DE TIREOIDE E TIREOIDITE DE HASHIMOTO.............................................................. 33
Gama RR1; Talini C1; Kaminski JH1 PO002 ABLATION IN LOW RISK PAPILLARY THYROID CANCER. YES OR NO COMPARISON OF 3 METHODS....................... 33
Degrossi E1; Degrossi O1; Baubuena R2
PO003 RESPONSE TO SORAFENIB IN METASTATIC ADVANCED THYROID CARCINOMA......................................................... 33
Pitoia F1
PO004 OUTCOME OF PATIENTS WITH DIFFERENTIATED THYROID CANCER ACCORDING TO ATA AND LATS
RISK OF RECURRENCE CLASSIFICATIONS....................................................................................................................... 33
Pitoia F1; Abelleira E1; Bueno F1; Urciuoli C1; Salvai ME1; Cross G1; Niepomniszcze H + (in memoriam) 1
PO005 INDOLENT OUTCOME OF PATIENTS WITH DIFFERENTIATED THYROID CANCER AND BIOCHEMICAL
PERSISTENCE OF DISEASE................................................................................................................................................. 34
Pitoia F1; Abelleira E1; Bueno F1; Urciuoli C1; Niepomniszcze H (in memoriam)1
PO006 ANÁLISE DO ESVAZIAMENTO DO COMPARTIMENTO CENTRAL PROFILÁTICO EM PACIENTES
SUBMETIDOS À TIREOIDECTOMIA TOTAL POR CARCINOMA PAPILÍFERO DE TIREOIDE............................................ 34
Montoro JRMC1; Miranda FA1; Degrande MP1; Pretti VP1; Arruda GV1; Affonso VR1; Uvo SAB1
PO007 METÁSTASE CÍSTICA CERVICAL COMO PRIMEIRA MANIFESTAÇÃO DO CARCINOMA PAPILÍFERO
DE TIREOIDE......................................................................................................................................................................... 34
Oliveira-Filho JRF1; Rodrigues MM1; Santos VJB1; Nadai TR1
PO008 TECIDO TIREOIDIANO ECTÓPICO EM LINHA MÉDIA ASSOCIADO À TIREOIDITE DE HASHIMOTO............................. 35
Oliveira-Filho JRF1; Nadai TR1; Rodrigues MM1; Santos VJB1
PO009 CARCINOMA TIROIDEO LOCALMENTE INVASIVO EN TRÁQUEA. TRATAMIENTO ONCOLÓGICO Y POSTERIOR
TRAQUEOPLASTÍA ALEJADA POR DEHISCENCIA DE ANASTOMOSIS TRAQUEAL....................................................... 35
Zund S1; Patané K2; Califano I1; Lupo E1; Rufino C1; Saco P1 PO010 METÁSTASES SINCRÔNICAS PARA TIREOIDE E PULMÃO DE ADENOCARCINOMA NO INTESTINO........................... 35
Silva SJ1; Mamede JF1; Moraes1; Silva MVF1; Silva VTTM1; Cordeiro MS1; Ferreira KS1
PO011 ENFERMEDAD DE GRAVES: VENTAJAS DEL TRATAMIENTO COMBINADO METIMAZOL + T3 EN RELACIÓN A
METIMAZOL SOLO............................................................................................................................................................... 35
Vázquez A1; Calabrese C1; Alcaraz G1; Abalovich M1; Calletti F1; Simoni Y1; Tkatch J1; Frydman M1; Levalle O1; Gutiérrez S1 PO012 HIPERTIROIDISMO, VASCULITIS ASOCIADA A PROPILTIOURACILO............................................................................... 36
Jiménez M1; Gottchaslk C1; Iturrieta V2; Granzotto C1; Sepúlveda G1; Roa JC1; Schnerberger P1
PO013 COLESTIRAMINA: ALTERNATIVA TERAPÉUTICA EN EL TRATAMIENTO DEL HIPERTIROIDISMO................................. 36
Munizaga F1; Munizaga C1
PO014 TOTAL THYROIDECTOMY FOR GRAVES DISEASE: A GOOD OPTION FOR SELECTED CASES..................................... 36
Volpi EM1; Steck JH2; Vasconcelos ECG3; Mahmoud RRGL1; Aizawa RK1; Cernea CR1; Araujo Filho VJF1
PO015 OFTALMOPATIA DE GRAVES: QUADRO GRAVE COM ALTERAÇÕES HORMONAIS LEVES: RELATO DE CASO........... 37
Pontes AAN1; Pequeno TA1; Meneguesso AMA1; Matos LL1; Sena CM1; Rêgo ACC1; Capote Júnior JRFG1
PO016 SPINDLE EPITHELIAL TUMOR WITH THYMUS-LIKE DIFFERENTIATION (SETTLE) IN A 12-YEARS-OLD MALE........... 37
Da Silva PCA1; Nascimento PR1; Lee JS1; Nascimento ML1; Cechinel E1; Linhares RMM1; Simoni G1; Aust J2; Vieira D2
PO017 SELECTIVE INDICATION OF PROPHYLACTIC CENTRAL NECK DISSECTION IN PAPILLARY THYROID CANCER........ 37
De Carvalho AY1; Chulam TC1; Fernandes WB1; Kowalski LP1
3
Sumário
PO018 STATISTICAL CASES OF DIFFERENTIATED THYROID CARCINOMA IN A GOVERNMENT HOSPITAL
OF SÃO PAULO..................................................................................................................................................................... 38
Bueno TL1; Guerra RA1; Portes ES1; Santos LM1; Ramalho MCB1; Vale AMC1
PO019 INCIDÊNCIA DO CÂNCER DE TIREOIDE EM PACIENTES TIREOIDECTOMIZADOS NA CIDADE DE
ARAGUAÍNA – TOCANTINS.................................................................................................................................................. 38
Coelho T1; Feltrim EN1; Medrado R1
PO020 COMPLICATIONS IN THYROIDECTOMY: NOW AND THEN................................................................................................ 38
Lira RB1; Fiho JG1; Kowalski LP1
PO021 RELAÇÃO DOS NÍVEIS DO HORMÔNIO ESTIMULANTE DA TIREOIDE (TSH) COM A MALIGNIDADE
EM NÓDULOS DE TIREOIDE................................................................................................................................................ 39
Colombo BS1; Conceição TMB2; Canalli JS2; Colombo G1; Pasinato APBF1; Schneider IJC2; Canalli MHBS1
PO022 COMPARAÇÃO ENTRE TERMOGRAFIA E DOPPLER DE NÓDULOS TIREOIDIANOS BIOPSIADOS............................... 39
Alves MLD1; Duarte GG2; Gabarra MHC1
PO023 THYROID NODULES AND RISK FACTORS ASSOCIATED WITH MALIGNANCY............................................................... 39
Coelho SFM1; Bezerra FSM1; Ferraz TMBL1; Mota RMS1; Macedo LML1; Mota JIS1
PO024 ¿PUEDE LA ECOGRAFÍA CON POWER DOPPLER AYUDAR EN LA PREDICCIÓN DE MALIGNIDAD
DE LOS NÓDULOS TIROIDEOS?.......................................................................................................................................... 40
Munizaga F1 PO025 ESTUDIO ECOGRÁFICO DE TIROIDES EN PACIENTES CON ACROMEGALIA................................................................. 40
Millar ES1; Véliz J1; Díaz RE1; Rojas D2; García M3; Brantes S1; Wohllk N1 PO026 ANALYSIS OF PRE-THYROGLOBULIN DOSE OF RADIOACTIVE IODINE IN PATIENTS WITH DIFFERENTIATED
THYROID CARCINOMA......................................................................................................................................................... 40
Bueno TL1; Guerra RA1; Portes ES1; Ferro KM1; Marocco TS1
PO028 EVALUATION OF PERCUTANEOUS ETHANOL INJECTION AS THYROID NODULES TREATMENT................................. 41
Piaia C1; Cadore AC1; Ferreira MC2
PO029 NON-SURGICAL MANAGEMENT OF BENIGN THYROID CYSTS: EVALUATION OF 79 CASES OF
ULTRASOUND GUIDED ETHANOL SCLEROTHERAPY....................................................................................................... 41
Marchi MFS1; Bonamigo LF1; Couto CH2; Barros RC3
PO030 OCCURRENCE OF SARCOIDOSIS IN A PATIENT THAT HAS PREVIOUSLY UNDERWENT
PERCUTANEOUS ETHANOL ABLATION OF A SOLID THYROID NODULE........................................................................ 41
Marchi MFS1; Kuhn M1; Couto CH2
PO031 TRATAMIENTO CON CORTICOIDES ENDOVENOSO EN OFTALMOPATÍA DE GRAVES................................................... 41
Zunino A1; Delfino L1; Ilera V1; Sapia V1; Silva Croome MC1; Gauna A1 PO032 OFTALMOPATÍA DE GRAVES: PREVALENCIA, CLÍNICA Y FACTORES DE RIESGO......................................................... 42
Zunino A1; Delfino L1; Ilera V1; Sapia V1; de Viale P; Silva Croome MC1; Gauna A1 PO033 TREATMENT OF GRAVES’ OPHTHALMOPATHY WITH A PPAR-g ANTAGONIST AND COX-2 INHIBITOR
(SODIUM DICLOFENAC): A CRITICAL REVIEW................................................................................................................... 42
Mimura LY1; Moura JP1; Bloise W2
PO034 THE SYSTEM IGF-1/IGF-1 RECEPTOR AS A PROBABLE LINK BETWEEN EUTHYROID GRAVES’
OPHTHALMOPATHY AND PAPILLARY THYROID CARCINOMA......................................................................................... 42
Moura JP1; Monteiro MLR2; Mimura LY1; Siqueira SAC3; Dias EO4; Nicolau W1; Bloise W1
PO035 PREGNANCY THYROID FUNCTION AT HOSPITAL UNIVERSITARIO AUSTRAL................................................................ 43
Urrutia MA1; Guerra JL1; Borracci R1; Alcoba Gutierrez ME1; Fregonese R1; De Carli E1; Chazarreta D1; Patton NM1; Rojas M1;
Beruti E1Negueruela MC1
PO036 DOENÇA TIREOIDIANA AUTOIMUNE E DIABETES MELLITUS TIPO 1 ............................................................................ 43
Coelho ATM1; Rusch AS1; Schmitt-Lobe MC1
PO037 A MORE THEN CAUSAL ASSOCIATION BETWEEN GRAVES’ DISEASE AND MIASTHENIA GRAVIS.............................. 43
Schrank Y1; Correa ND; Braga N1
PO038 SEVERE HEPATITIS RELATED TO GRAVES’ DISEASE CONTROLLED WITH ANTITHYROID DRUGS:
CASE REPORT...................................................................................................................................................................... 44
Amaral SS1; Macedo LML1; Alcantara ANS1; Silva PSA1; Costa MCM1; Ferraz TMBL1
PO039 ASSOCIAÇÃO DE DOENÇA DE GRAVES E HEPATITE AUTOIMUNE................................................................................. 44
Maia CP1; Corrêa MV1; Santos JCV1; Magalhães RSC1; Reis MDSL1; Tonet C1; Messias ACNV1; Mansur VAR1
4
Sumário
PO040 PREVALENCE OF HYPOTHYROIDISM IN PATIENTS WITH FROZEN SHOULDER............................................................ 44
Shiefer M1; Teixeira PFS1; Castro O2; Silva NAO1; Conceição FL1
PO041 IMPLICATIONS OF INTERATRIAL SEPTUM ABNORMALITIES AMONG HIPERTHYROID PATIENTS WITH ATRIAL
FIBRILLATION – A CROSS SECTION ANALYSIS WITH TRANSOESOPHAGEAL ECHOCARDIOGRAPHY....................... 45
Souza MV1
PO042 FOREARM BLOOD FLOW IN WOMEN WITH SUBCLINICAL HYPOTHYROIDISM............................................................. 45
Ghetti FF1; Lacerda RP1; Werneck FZ2; Coelho EF2; Teixeira PFS2; Vaisman M2; Lima JRP1; Laterza MC1 PO043 AVALIAÇÃO DO ESPESSAMENTO MÉDIO-INTIMAL DE CARÓTIDAS EM PACIENTES COM HIPOTIREOIDISMO
SUBCLÍNICO, COM OU SEM SÍNDROME METABÓLICA.................................................................................................... 45
França MM1; Hueb JC1; Padovani CR1; Nogueira CR1; Mazeto GMFS1
PO044 OXYGEN UPTAKE KINETICS ARE SLOWED IN SUBCLINICAL HYPOTHYROIDISM......................................................... 45
Werneck FZ1; Coelho EF1; Lima JRP2; Laterza MC2; Bonfante HLM3; Barral MM3; Teixeira PFS1; Vaisman M1
PO045 CASE REPORT: SEVERE HYPOTHYROIDISM LEADING TO CONGESTIVE HEART FAILURE.......................................... 46
Mastella LS1; Almeida SL1; Borges AP1; Bodanese LC1; Reppetto G1
PO046 DOSIS SUSTITUCIÓN TIROIDEA CON L-TIROXINA EN HIPOTIROIDISMO PRIMARIO SEGÚN ETIOLOGÍA
Y VOLUMEN TIROIDEO......................................................................................................................................................... 46
Munizaga F1
PO047 AVALIAÇÃO DO SERVIÇO DE REFERÊNCIA EM TRIAGEM NEONATAL NO ESTADO DE TOCANTINS
(SRTN-TO) NO PERÍODO DE 2007 A 2011........................................................................................................................... 46
Alves ARV1; Cruz MA2; Oliveira BS2; Nascimento SAR2; Araújo CMXB2; Alves Jr AM1
PO048 DETERMINING THE TSH REFERENCE VALUE: EXPERIENCE FROM THE CHILEAN NATIONAL
HEALTH SURVEY 2009-2010................................................................................................................................................ 47
Mosso L1; Margozzini P1; Solari S1; Dominguez MA1; Arteaga E1
PO049 ADESÃO AO TRATAMENTO DE HIPOTIREOIDISMO NO AMBULATÓRIO UNIVERSITÁRIO DE REFERÊNCIA
DA UNIVERSIDADE REGIONAL DE BLUMENAU/SC ......................................................................................................... 47
Thomazelli FCS1; Weissenberg C1; Augusto SB1
PO050 CARCINOMA PAPILÍFERO DE TIREOIDE: RELATO DE 2 CASOS COM EVOLUÇÃO INESPERADA................................ 47
Corrêa ND1; Schrank Y1; Araujo NBC1; Netto IG1
PO051 PROPHYLACTIC NECK DISSECTION IN DTC. IS IT WORTH IT?....................................................................................... 48
Volpi EM1; Omokawa M1; Bertelli AAT2; Massarollo LCB3; Steck JH4; Cernea CR1
PO052 IMPACT OF TUMOUR SIZE IN THE OUTCOME OF PATIENTS WITH PAPILLARY THYROID
MICROCARCINOMA BASED ON A SERIES OF 218 CASES............................................................................................... 48
Gonçalves Filho J1; Quiroa LR1; Kowalski LP PO053 TRATAMIENTO DE BOCIOS MULTINODULARES MIXTOS CON I-131 E INYECCIONES DE ETANOL
EN FORMA COMBINADA...................................................................................................................................................... 48
Jara Yorg JA1; Jara MA; Jara Ruiz JM; Jara Ruiz ED1 PO054 RELAÇÃO BÓCIO MERGULHANTE E SÍNDROME DA VEIA CAVA SUPERIOR.................................................................. 48
Leão JRB1; Ribeiro RX1; Normanha LL1; Vento L1
PO055 EL 2-IODOHEXADECANAL MODULA NEGATIVAMENTE A NIS A TRAVÉS DE LOS PPARS............................................. 49
Rossich LE1; Nazar M2; Thomasz L1; Salvarredi LA1; Olgio R1; Nicola JP2; Pisarev MA1; Masini RAM2; Juvenal GJ1 PO056 EFECTO ANTI-TUMORAL DE LA 6-IODO-DELTA-LACTONA (IL-D) EN CÉLULAS DE CÁNCER DE COLON................... 49
Thomasz L1; Salvarredi L1; Perona M1; Oglio R1; Rossich L1; Pisarev M2; Juvenal G3 PO057 NEW CHANGES IN DUOX2 GENE IN PATIENTS WITH DYSHORMONOGENESIS CAUSED BY IODIDE
ORGANIFICATION DEFECT.................................................................................................................................................. 49
Brust ES1; Marui S1
PO058 MOLECULAR CHARACTERIZATION OF THE I- TRANSPORT DEFECT-CAUSING D287-288 NA+/I- SYMPORTER
MUTANT UNCOVERS RESIDUES INVOLVED IN NA+ BINDING/TRANSLOCATION........................................................... 50
Nicola JP1; Reyna-Neyra A1; Carrasco N1
PO059 LOW T3 SERUM LEVELS AND BAT IODOTHYRONINE DEIODINASE ACTIVITY ARE ASSOCIATED WITH
IMPARIED METABOLIC FUNCTION IN A MODEL OF ANXIETY DISORDER........................................................................... 50
Mousovich-Neto F1; Landeira-Fernandes J2; Correa da Costa VM1
PO060 EVALUATION OF HEART RATE VARIABILITY IN RATS WITH SUBCLINIC HYPOTHYROIDISM........................................ 50
Apocalipse JCC1; Pilissari A1; Saviolli IH1; Duarte JS1; Sato MA1; Giannocco G1 5
Sumário
PO061 HYPOTHYROXINEMIA DURING PREGNANCY ALTERS NEURONAL PROJECTIONS AND THE
ESTABLISHMENT OF SYNAPSE IN THE THEIR PROGENY................................................................................................ 51
Cisternas P1; Zuñiga G1; Opazo MC1; Santibañez M2; Bueno S3; Kalergis A3; Riedel C1
PO062 INFLUÊNCIA DA TEMPERATURA AMBIENTAL NO NÍVEL DE TSH SÉRICO...................................................................... 51
Francescantonio ICM1; Rezende KN1; Borges ALF1; Castro MEC1; Francescantonio ICCM1
PO063 REGULAÇÃO DA EXPRESSÃO HEPÁTICA DE MCT8 POR T3 DEPENDE DA INTEGRIDADE DO TRb............................ 51
Almeida HN1; Pereira GF1; Império GE2; Santiago LA2; Ortiga-Carvalho TM1
PO064 AÇÕES RÁPIDAS DA TRI-IODOTIRONINA (T3) SOBRE A EXPRESSÃO GÊNICA DA
PRÓ-OPIOMELANOCORTINA.............................................................................................................................................. 52
Prévide RM1; BARGI-SOUZA P1; NUNES MT1
PO065 THYROID HORMONE INCREASES SEMAPHORIN 5A AND 5C GENE EXPRESSION IN RAT CORTEX
AND HIPPOCAMPUS............................................................................................................................................................ 52
Duarte JS1; Sato MA1; Giannocco G1; Souza JS2; Maciel RMB2
PO066 UP-REGULATION AMPHIREGULIN MRNA BY ACTION INDIRECTLY OF TRIIODOTHYRONINE VIA
ESTROGEN RECEPTOR ACTIVATION.................................................................................................................................. 52
Sibio MT1; Carbonera ACL1; Oliveira M1; Olimpio RMC1; Moretto FCF1; Luvizotto RAM1; Fecchio D1; Nogueira CR1
PO067 SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA OF THE THYROID GLAND:
CASE REPORT AND REVIEW OF LITERATURE................................................................................................................... 52
Ferro KM1; Bueno TL1; Afonso GLP1; Guerra RA1; Portes ES1; Oliveira OCG1; Ribas MH1; Lehn CN1 PO068 THE ROLE OF ANGIOGENESIS MARKERS IN PHEOCHROMOCYTOMA.......................................................................... 53
Ferreira CV1; Siqueira DR1; Romitti M1; Ceolin L1; Cavalcante S1; Capp C1; Brasil BA2; Meurer L2; Maia AL1
PO069 SORAFENIB IN THE TREATMENT OF IODINE- RESISTANT THYROID CARCINOMA....................................................... 53
Danilovic DLS1; Lerario MA2; De Castro Jr G3; Camargo RYA4; Hoff AO2
PO070 USO DE TSH RECOMBINANTE EM PACIENTE APÓS SURTO PSIQUIÁTRICO: UMA ALTERNATIVA
À PESQUISA DE METÁSTASE NO CARCINOMA DIFERENCIADO DE TIREOIDE.............................................................. 53
Biancardi NF1; Biancardi MF1; Barcelos RN2; Pacheco CFV1
PO071 SERTRALINE CAN BE USEFUL PRE-131 RADIOIODINE DOSIS IN PATIENTS WITH THYROID CANCER....................... 54
MNC Silva1; Almeida MG1; Rath R2; Silva PCA3
PO072 IDENTIFICATION OF NOVEL VARIANTS OF RET ONCOGENE POTENTIALLY LINKED TO THE
PATHOGENESIS OF PHEOCHROMOCYTOMA AND MEDULLARY THYROID CARCINOMA............................................ 54
Bim LV1; Delcelo R2; Lima Jr JV3; Maciel RM4; Cerutti JM1
PO073 THE ROLE OF GENETIC VARIANT IN THE 3’UTR OF THE RET PROTO-ONCOGENE ON S836S
POLYMORPHISM-ASSOCIATED CLINICAL COURSE OF MEDULLARY THYROID CARCINOMA.................................... 54
Ceolin L1; Siqueira DR1; Romitti M1; Ferreira CV1; Maia AL1
PO074 THE B-RAFV600E MUTATION IS NOT ASSOCIATED WITH POORER CLINICAL PROGNOSIS IN
PAPILLARY THYROID CANCER........................................................................................................................................... 55
Scheffel RS1; Romitti M1; Antunes D1; Pinto Ribeiro RV1; Ceolin L1; Dora JM1; Maia AL1
PO075 INVESTIGAÇÃO DE UM POSSÍVEL EFEITO FUNDADOR EM FAMÍLIAS COM NEOPLASIA ENDÓCRINA
MÚLTIPLA TIPO 2 E DUPLA MUTAÇÃO P.C634Y/P.Y791F NO GENE RET........................................................................ 55
Fonseca CCN1; Bastos AU1; Valente FOF1; Maciel RMB1; Cerutti JM1
PO076 ESTABILIDAD DE LA MEDICIÓN DE CALCITONINA INMUNO-REACTIVA EN MUESTRAS PROVENIENTES
DEL LÍQUIDO DE LAVADO DE PUNCIÓN CON AGUJA FINA.............................................................................................. 55
Piotrkowski-Viale F1; Dios A1; Lowenstein A1; Reyes A1; Glikman P1 PO077 UTILIDAD CLÍNICA DE ANTICUERPOS ANTITIROGLOBULINA EN EL SEGUIMIENTO DEL CÁNCER
DIFERENCIADO DE TIROIDES. ESTUDIO RETROSPECTIVO............................................................................................. 56
Millar ES1; Utreras C1; Díaz RE1; Véliz J1; Wohllk N2 PO078 ANOMALOUS THYROGLOBULIN – A NEW PUZZLE FOR A WELL KNOWN PROTEIN?.................................................. 56
Xavier ACW1; Kasamatsu TS1; Oliveira KC1; Harada MY1; Mendes A2; Meneghetti MCZ2; Lima MA2; Kunii IS1; Furuzawa GK1;
Ikejiri E1; Mamone MCC1; Maciel RMB1; Vieira JGH1; Dias da Silva MR1; Martins JRM3; PO079 RELATION BETWEEN POSTOPERATIVE STIMULATED THYROGLOBULIN AND FOLLOW-UP WITH
SERUM THYROGLOBULIN FOR THYROID CARCINOMA................................................................................................... 56
Lira RB1; Chulam TC1; De Carvalho AY1; De Carvalho GB1; Kowalski LP1
PO080 IS POSTOPERATIVE RADIOIODINE THERAPY HELPFUL IN FOLLOW-UP USING SERUM THYROGLOBULIN?............ 57
Lira RB1; De Carvalho AY1; Vartanian JG1; Filho JG1; Kowalski LP1
6
Sumário
PO081 CARACTERIZAÇÃO DE CURVA ANALÍTICA PARA DETERMINAÇÃO DO IODO NO LEITE MATERNO............................ 57
Catarino RM1; Martini F1; Peres NS1; Ferreira JE1; Maeda MYS1; Santos RTM1 PO082 VALIDADE DA REPETIÇÃO DA PUNÇÃO BIÓPSIA ASPIRATIVA PARA NÓDULOS DE TIREOIDE................................... 57
Graciano AJ1; Ferreira SJ1; Fischer CA1; Peixoto AJA1; Bublitz GS2
PO083 PAAF DE NÓDULOS TIROIDEOS GUIADA POR ECOTOMOGRAFÍA. VALOR DEL TIRADS.............................................. 58
Jiménez M1; Sapunar J1; Granzotto C1; Roa JC1; Gayoso R1; Huenchullan C1 PO084 INCREASE OF METALLOPROTEINASES (MMPS) ACTIVITY AND MIGRATORY ABILITY OF THYROID
TUMOR CELLS INDUCED BY TUMOR CELL-FIBROBLAST INTERACTION...................................................................... 58
Della Vedova AB1; Remedi MM1; Gilardoni MB1; Masini-Repiso AM1; Pellizas CG1; Donadio AC1 PO085 USO DEL SISTEMA BETHESDA EN CITOLOGÍAS DE ALTO RIESGO DE PUNCIONES BIOPSIAS TIROIDEAS.............. 58
Gutnisky L1; Delfino L1; Laudi R1; Deira S1; Rivadeneira S1; Santander M1; Olstein G1; Reyes A1; Lowenstein A1
PO086 ANÁLISE CITO-HISTOPATOLÓGICA DOS NÓDULOS TIREOIDIANOS SUSPEITOS (BETHESDA IV/V)............................ 59
Silva MC1; Pereira CG1; Colombo BS1; Ronsoni MF1; Hohl A1; Vieira DSC1; Canalli MHBS1
PO087 CLINICAL AND PATHOLOGIC FEATURES OF SPORADIC AND FAMILIAR PAPILLARY THYROID CARCINOMA
IN CHILDREN, ADOLESCENTS AND YOUNG ADULTS....................................................................................................... 59
Medeiros MFS1; Pereira DP1; Strappa GBS1; Souza M1; Lima CRA2; Fonseca Jr LE3; Silva IC4; Lobão LJ5; Ramos HE1
PO088 CARCINOMA PAPILAR TIROIDEO. RECIDIVA TARDÍA CON METÁSTASIS MÚLTIPLES................................................... 59
Sepúlveda A1; Eugenin D2 PO089 NÓDULO PARASÍTICO DE TIREOIDE ASSOCIADO A BÓCIO MULTINODULAR ATÓXICO............................................... 59
PO090 CONTRIBUTION OF THE BIOLOGICAL DOSIMETRY FOR TREATMENT DECISIONS IN PATIENTS WITH
DIFFERENTIATED THYROID CARCINOMA (DTC) UNDER RADIOIODINE-131 THERAPY................................................ 60
Chebel GM1; Di Giorgio M2; Radl A2; Taja MR2; Bubniak R2; Deminge M2; Oneto A3; Fadel AM1
PO091 ANALYSIS OF MOLECULAR PROFILE OF PEDIATRIC THYROID CANCER....................................................................... 60
Cordioli MICV1; Moraes LS1; Besson PS1; Delcelo R1; Alves MTS1; Monte O2; Longui CA2; Cury AN2; Cerutti JM1
PO092 ANÁLISIS DE MUTACIÓN DEL ONCOGEN BRAF EN POBLACIÓN ARGENTINA.............................................................. 60
Ilera V1; Dourisboure R1; Colobraro A1; Silva Croome MC1; Olstein G1; Zunino A1; Lowenstein A1; Reyes A1; Gauna A1 PO093 DREAM MUTATIONS MAY BE INVOLVED IN PAPILLARY THYROID CARCINOMA DEVELOPMENT................................ 61
Batista FA1; Bufalo NE1; Silva ACN1; Marcello MA1; Cardoso UO1; Assumpção LVM1; Silva MJ2; Ward LS1
PO094 CHEMOKINES AS PROGNOSTIC MARKERS OF THE PAPILLARY THYROID CARCINOMA............................................ 61
Francescantonio ICM1; Silva CMN1; Modesto DC1; Nunes LM1; Marques LRS1; Saddi VA1; Wastowski JI1 PO095 VEGF EXPRESSION AND SONOGRAPHIC FEATURES IN BENIGN THYROID NODULES ASSOCIATED TO
HASHIMOTO’S THYROIDITIS............................................................................................................................................... 61
Maia FFR1; Vassallo J2; Pinto GA3; Pavin EJ1; Matos PS4; Zantut-Wittmann DE1 PO096 ASSOCIATION AMONG CTLA4, PTPN22 AND IFIH1 POLYMORPHISMS AND CHILDREN WITH GRAVES’
DISEASE AND HASHIMOTO’S THYROIDITIS WITH OR WITHOUT TYPE 1 DIABETES..................................................... 62
Bedin MR1; Trarbach EB1; Maciel LMZ2; Guerra-Jr G3; Queiroz M4; Manna TD5; Damiani D5; Marui S1
PO097 THE ACTIONS OF 3,5-DIIODOTHYRONINE, 3,5,3’–TRIIODOTHYRONINE AND THYROXINE ON PAPILLARY
THYROID CARCINOMA CELL LINE VIABLITY..................................................................................................................... 62
Coelho RG1; Carvalho DP1
PO098 RADIOSENSIBILIZACIÓN DE LÍNEAS CELULARES DE CÁNCER DE TIROIDES POR INHIBIDORES DE
HISTONAS DEACETILASAS.................................................................................................................................................. 62
Perona M1; Thomasz L1; Rossich L2; Casal M1; Pisarev MA1; Juvenal G1 PO099 INFLUÊNCIA DE FAM83F, INTEGRANTE DE UMA NOVA FAMÍLIA DE GENES TUMORAIS, NO CARCINOMA
ANAPLÁSICO DE TIREOIDE................................................................................................................................................. 63
Silva LR1; Fuziwara CS1; Kimura ET1
PO100 AVALIAÇÃO DA EXPRESSÃO LIN28 “RNA BINDING-PROTEIN” E LET-7 NO CARCINOMA TIREOIDIANO..................... 63
Olivé AN1; FuziwaraCS1; Kimura ET1 PO101 EFEITOS DO 17B-ESTRADIOL SOBRE A GERAÇÃO DE H2O2 E EXPRESSÃO DE TGF-BETA E
METALOPROTEASES EM CÉLULAS PCCL3....................................................................................................................... 63
Hecht F 1; Ortenzi VH1; Carvalho DP1; Fortunato RS1
PO102 NÍVEL DE PARATORMÔNIO APÓS TIREOIDECTOMIA TOTAL COMO PREDITOR DE HIPOCALCEMIA
SINTOMÁTICA – ESTUDO PROSPECTIVO.......................................................................................................................... 63
Gama RR1; Fezer GF1; Delfes RA1
7
Sumário
PO103 ALTERAÇÕES METABÓLICAS E TIREOIDITE DE HASHIMOTO......................................................................................... 64
Ronsoni MF1; Ferreira L1; Oliveira MP1; Colombo BS1; Silva MC1; Michels J1; Coral MHC1; Hohl A1
PO104 CORRELAÇÃO ENTRE ALT, GGT E CARACTERÍSTICAS CLÍNICAS E LABORATORIAIS EM PORTADORES DE
TIREOIDITE DE HASHIMOTO............................................................................................................................................... 64
Ronsoni MF1; Ventura A1; Canalli MHBS1; Hohl A1; Dantas-Corrêa EB1; Schiavon LL1; Narciso-Schiavon JL1
PO105 SELECTIVE TREATMENT FOR HYPOPARATHYROIDSM AFTER TOTAL THYROIDECTOMY BASED
ON PTH LEVELS.................................................................................................................................................................... 64
Bertelli AA1; Kikuchi W1; Derito CP1; Möller LG1; Hirota LN1; Garcia VA1; Suehara AB1; Gonçalves AJ1; Menezes MB1
PO106 ASSOCIATION OF TSH LEVEL TO METABOLIC AND ANTHROPOMETRY PARAMETERS IN OVERWEIGHT
EUTHYROID ADOLESCENTS............................................................................................................................................... 65
Souza LL1; Guedes EP1; Moreira RO2; Godoy-Matos AF2; Vaisman M3 PO107 A GIANT GOITER: AN ILLUSTRATIVE CASE........................................................................................................................ 65
Alcântara ANS1; Silva PSA1; Ferraz TMBL1; Macedo RBL1; Amaral SS1; Muniz AA1
PO108 AVALIAÇÃO DA RESPOSTA À IODOTERAPIA NO TRATAMENTO DO HIPERTIREOIDISMO DA DOENÇA
DE GRAVES........................................................................................................................................................................... 65
Gama MPR1; Raymundo AR1; Costa CF1; Debortoli J1; Gama RR1
PO109 MARROW HYPOPLASIA: A RARE COMPLICATION OF UNTREAT GRAVES DISEASE..................................................... 66
Rodrigues BS1; Garcia JCA1; França LBC1; Torrini RC1; Caldas D1; Campos CFC1
PO110 AGRANULOCITOSE INDUZIDA POR METIMAZOL EM PACIENTE COM DOENÇA DE GRAVES...................................... 66
Foppa A1; Alves JM2; Dos Santos EC1; Dos Santos AA1; Fiorin D3; Teixeira NM3; de Carvalho GA3;
PO111 DOENÇA AUTOIMUNE DA TIREOIDE: DO HIPO AO HIPERTIREOIDISMO – RELATO DE CASO..................................... 66
Rocha AM1; Pontes AAN1; Capote Júnior JRFG1; Sena CM1; Torres MR1; Pequeno TA1; Rocha BAM2
PO112 THYROTOXIC CRISIS SUPERIMPOSED TO LIVER DISEASE: REPORT OF 2 CASES ..................................................... 67
Macedo LML1; Silva PSA1; Coelho SFM1; Amaral SS1; Acântara ANS1; Costa MCM1
PO113 SUCCESS RATES IN GRAVES’ DISEASE WITH A SINGLE LOWER RADIOIODINE DOSE................................................ 67
Huachin Soto MK1; Norieha Ruiz VH1; Torres Samame LDR1; Molina Calderon GI
PO114 CRISE TIREOTÓXICA E FALÊNCIA HEPÁTICA FULMINANTE: RELATO DE CASO E REVISÃO DA LITERATURA.......... 67
Contrucci AC1; Santomauro ATMG2; Paula CA2; Fraige Filho F2; Arçari GD2; Carvalho ITI2; Magalhães JF2; Capps LM1; Silva PPB2;
Bacchin RP2
PO115 HIPERTIREOIDISMO CAUSADO PELA DOENÇA DE GRAVES EM PACIENTE PORTADOR DE DOENÇA
RENAL CRÔNICA TERMINAL: RELATO DE CASO.............................................................................................................. 68
Satomauro ATMG1; Paraguassu BR1; Paula CA1; Fraige Filho F1; Vieira MCC1; Dallal MVS1; Pereira NGB1; Valle PO1;
Costa PS1; Correa RC1
PO116 AVALIAÇÃO DA RELAÇÃO DE DOSAGENS SÉRICAS DE HORMÔNIO TIREOESTIMULANTE COM GÊNERO
E IDADE EM UM GRUPO DE INDIVÍDUOS DE GOIÂNIA, GOIÁS, BRASIL......................................................................... 68
Almeida AR1; Melo MA1; Botacin LS1; Ferro LM1; Miranda TMT1; Francescantonio ICCM1; Rezende KN1 PO117 PREVALÊNCIA E DIAGNÓSTICO PRECOCE DE HIPOTIREOIDISMO SUBCLÍNICO, UTILIZANDO-SE DIFERENTES
VALORES DE REFERENCIA PARA TSH, EM GOIÂNIA, GOIÁS, BRASIL............................................................................ 68
Normanha LL1; Ribeiro RX1; Leão JRB1; Vento L1; Vieira MB1; Miranda TMT1
PO118 AVALIAÇÃO DOS ÍNDICES HEMATIMÉTRICOS DE PACIENTES COM HIPOTIREOIDISMO SUBCLÍNICO
ATENDIDOS EM EVENTO COMUNITÁRIO EM GOIÂNIA, GOIÁS, BRASIL......................................................................... 68
Ribeiro RX1; Normanha LL1; Leão JRB1; Vento L1; Vieira MB1; Francescantonio ICCM1; Miranda TMT1
PO119 RELAÇÃO ENTRE TSH, CREATININA E UREIA................................................................................................................... 69
Francescantonio ICM1; Rezende KN1; Borges ALF1; Francescantonio ICCM1
PO120 ADEQUATE LEVOTHYROXINE DOSES FOR THE TREATMENT OF SUBCLINICAL AND OVERT HYPOTHYROIDISM
NEWLY DISCOVERED DURING PREGNANCY..................................................................................................................... 69
Abalovich M1; Vázquez A1; Alcaraz G1; Calabrese C1; Kitaigrodsky A1; Szuman G1; Astarita G1; Frydman M1; Gutiérrez S1
PO121 IMPACTO DEL EMBARAZO EN LA EVOLUCIÓN DEL CARCINOMA DIFERENCIADO DE TIROIDES.
NUESTRA EXPERIENCIA A LO LARGO DE 22 AÑOS......................................................................................................... 69
Alcaraz G 1; Vázquez A2; Abalovich Marcos2; Calabrese C2; Frydman M2; Gutiérrez S2; Chebel G3; Fadel AM4 PO122 PLASMA SELENIUM LEVELS IN NEGATIVE THYROID PEROXIDASE ANTIBODY PREGNANT WOMEM
AND ITS RELATION TO ABORTION AND PREMATURE DELIVERY.................................................................................... 70
Mancini MM1; Teixeira PFS1; Silva NAO2; Coeli CM1; Vaisman M1
PO123 PERFIL TIROIDEO EN UNA POBLACIÓN DE EMBARAZADAS SANAS DE LA CIUDAD AUTÓNOMA
DE BUENOS AIRES............................................................................................................................................................... 70
Rodríguez MF1; Silva Croome MC1; Lutzky C2; Ilera V3; Zunino A3; Glikman P3; Serrano López D3; Scalise C3; Gauna A1
8
Sumário
PO124 IDENTIFICAÇÃO DA VIA DE DEGRADAÇÃO DO COTRANSPORTADOR SÓDIO-IODETO INDUZIDA PELA
CINASE ATIVADA POR AMP................................................................................................................................................. 70
Cazarin J1; Andrade BM1; Carvalho DP1
PO125 TREATMENT WITH FLAVONOID RUTIN INCREASES THYROID RADIOIODIDE UPTAKE................................................. 71
Gonçalves CFL1; Santos MCS1; Carvalho DP1; Ferreira ACF1
PO126 INFLUÊNCIA DA DENSIDADE CELULAR SOBRE A FUNÇÃO DO COTRANSPORTADOR NA+/I- EM CULTURA
DE CÉLULAS PCCL-3........................................................................................................................................................... 71
Lima LP1; Cortez R1; Ferreira ACF1; Carvalho DP1
PO127 IDENTIFICATION OF G-PROTEIN COUPLED RECEPTOR 30 (GPR30/GPER) IN HUMAN NORMAL
THYROID CELLS................................................................................................................................................................... 71
Santin AP1; Loureiro SO1; Pessoa-Pureur R1; Brum IS1; Furlanetto TW1
PO128 THYROID HORMONES (THS) REGULATE THE EXPRESSION OF MRNA OF PROTEINS RESPONSIBLE
FOR IRON HOMEOSTASIS IN LIVER OF RATS.................................................................................................................... 71
Sena-Souza J1; Duarte JS2; Maciel RMB1; Giannocco G2 PO129 ANTI-TUMOR IMMUNE RESPONSE MODULATION BY THYROID STATUS INFLUENCES THE DISSEMINATION
OF A MURINE T CELL LYMPHOMA..................................................................................................................................... 72
Sterle HA1; Valli E1; Paulazo MA1; Colombo L2; Barreiro Arcos ML1; Cremaschi GA3
PO130 ASSOCIAÇÃO DE T3 E E2 ATIVA C-FOS, RESPONSÁVEIS PELA ATIVAÇÃO OSTEOCLÁSTICA EM
OSTEOBLASTOS HUMANOS DERIVADOS DE TECIDO ADIPOSO..................................................................................... 72
PPS1; Olimpio RMC1; Sibio MT1; Oliveira M1; Ferreira T1; Conde S1; Nogueira CR1
PO131 THYROID HORMONE STATUS INTERFERES WITH ESTROGEN TARGET GENE EXPRESSION IN BREAST
CANCER SAMPLES OF MENOPAUSAL WOMEN................................................................................................................ 72
Conde SJ1; Luvizotto RAM1; Síbio MT1; Nogueira CR1
PO132 ISOCITRATE DEHYDROGENASE 1 (IDH1) MUTATIONS ARE PRESENT IN A HIGH PREVALENCE IN THYROID
CARCINOMAS AND ARE ASSOCIATED WITH SPECIFIC HISTOLOGICAL SUBTYPES AND LARGER TUMORS............ 73
Moraes LS1; Carvalheira GMG1; Nozima BHN1; Bastos AU1; Besson PS1; Evangelinellis MM1; Hermely JP1; Cerutti JM1 PO133 PUNCIÓN INTRAQUIRÚRGICA DE TIROIDES PARA LA DETECCIÓN DE MUTACIÓN DEL ONCOGEN BRAF................ 73
Ilera V1; Silva Croome MC1; Dourisboure R1; Olstein G1; Colobraro A1; Zunino A1; Lowenstein A1; Reyes A1; Gauna A1
PO134 INCREASED EXPRESSION OF MATRIX METALLOPROTEINASE-9 AND THEIR INHIBITORS IN PAPILLARY
THYROID CARCINOMA: CLINICAL IMPLICATIONS............................................................................................................ 73
Pinto Ribeiro RV1; Romitti M1; Ceolin L1; Ferreira CV1; Wajner SM1; Meurer L1; Brazil BA1; Maia AL1
PO135 THYROTROPIN (TSH) REFERENCE RANGE IN ELDERLY PEOPLE: A POPULATION BASED STUDY IN
RIO DE JANEIRO................................................................................................................................................................... 74
Fontes R1; Coeli CR2; Aguiar F2; Vaisman M2
PO136 PERFIL DE POPULAÇÃO RASTREADA PARA DOENÇAS TIREOIDIANAS DURANTE CAMPANHA
“EXAMINE SUA TIREOIDE”.................................................................................................................................................. 74
Guedes LSM1; Brasileiro ES1; Arruda CCC1; Silva KF1; Torres FF1; Leite DSA1; Cruz NA1; Bezerra CSM1; Sampaio RAAF1;
Filho PCM1; Forti AC1; Façanha CFS2
PO137 TOMOGRAFÍA POR EMISIÓN DE POSITRONES Y EL DILEMA DEL MEDIASTINO.......................................................... 74
Califano I1; Reyes A2; Lowenstein A2; Coduti M1; Zarlenga C1; Salariato O1; Saco P1; Califano L1 PO138 MICROCARCINOMAS DE MUY BAJO RIESGO NO TRATADOS CON RADIOYODO......................................................... 75
Utreras C1; Díaz RE2; Ramos C3; Millar ES2; Véliz J2; Wohllk N4 PO139 ASSOCIAÇÃO ENTRE TIREOIDITE DE HASHIMOTO E CÂNCER DA TIREOIDE: ANÁLISE DE 49 CASOS...................... 75
Alcântara-Jones DM1; Lavinas-Jones JM1; Daltro R1; Pitangueira AC1; Alcântara FT1; Melo AFO1; Cardoso C1; Cruz VFG1 PO140 A SIMPLE METHOD OF SENTINEL LYMPH NODE BIOPSY CAN UPSTAGE 50% OF N0 DIFFERENTIATED
THYROID CANCER................................................................................................................................................................ 75
Steck JH1; Vasconcelos ECG2; Kulcsar MAV3; Bertelli AAT4; Hanaoka N5; Linek M1
PO141 COST OF ADJUVANT RADIOACTIVE IODINE TREATMENT IN PATIENTS WITH DIFFERENTIATED THYROID
CARCINOMA......................................................................................................................................................................... 75
Goncalves Filho J1; Roque GRF1; Kowalski LP1
PO142 THE MAPK PATHWAY REGULATES TYPE 3 DEIODINASE EXPRESSION IN PAPILLARY THYROID CARCINOMA......... 76
Romitti M1; Wajner SM1; Pinto Ribeiro RV1; Ceolin L1; Ferreira CV1; Rohenkohl HC1; Fuziwara CS2; Kimura ET2; Maia AL1
PO143 A RELAÇÃO DA POSITIVIDADE DOS ANTICORPOS ANTIPEROXIDASE E ANTITIREOGLOBULINA COM A
MALIGNIDADE EM NÓDULOS TIREOIDIANOS................................................................................................................... 76
Colombo BS1; Silva MC1; Conceição TMB2; Canalli JS2; Pasinato APBF1; Balthazar APS2; Canalli MHBS1,2 9
Sumário
PO144 COMPARACIÓN DE TRES PROTOCOLOS EXPERIMENTALES EN ESTUDIOS PRE CLÍNICOS PARA EL
TRATAMIENTO DEL CÁNCER DE TIROIDES, USANDO EL BUTIRATO DE SODIO EN COMBINACIÓN
CON LA TERAPIA POR CAPTURA NEUTRÓNICA EN BORO (BNCT)................................................................................. 76
Perona M1; Majdalani E1; Carpano M2; Rodríguez C1; Nievas S1; Olivera M1; Pisarev MA3; Cabrini R1; Juvenal G4; Dagrosa MA4 PO145 OPTIMIZACIÓN DE LA TERAPIA POR CAPTURA NEUTRÓNICA EN BORO (BNCT) PARA EL TRATAMIENTO DEL
CÁNCER DE TIROIDES MEDIANTE EL USO DEL INHIBIDOR DE HISTONAS DEACETILASAS BUTIRATO DE SODIO...... 77
Perona M1; Rodríguez C1; Carpano M1; Olivera MS1; Nievas S1; Thorp S1; Curotto P1; Pozzi E1; Kahl S2; Pisarev MA3; Juvenal G4;
Dagrosa MA4 PO146 EXPRESSION OF FAS, FASL, BCL-2 AND MCL-1 IN BENIGN THYROID NODULES WITH HASHIMOTO’S
THYROIDITIS: CLINICAL AND SONOGRAPHIC CORRELATION........................................................................................ 77
Maia FFR1; Vassallo J2; Pinto GA3; Pavin EJ1; Matos PS4; Zantut-Wittmann DE1 PO147 APOPTOTIC MARKERS EXPRESSION IN THYROID NODULES WITH A FIRST BENIGN CYTOLOGICAL
RESULT AND SUSPECT ULTRASOUND FOR MALIGNANCY............................................................................................. 77
Maia FFR1; Vassalo J2; Pinto GA3; Pavin EJ1; Matos PS4; Zantut-Wittmann DE1
PO148 ALTERAÇÕES CITOLÓGICAS EM NÓDULO TIREOIDIANO ASSOCIADO À DOENÇA DE GRAVES................................. 78
Tonet C1; Corrêa MV1; Zorzo PT1; Rosa LCGF1; Costa GRG2; Maia CP1; Mansur VAR1; Macedo LRW1; Messias ACNV1 PO149 EVALUATION OF SERUM TSH AS A PREDICTOR OF MALIGNANCY IN THYROID NODULES OF PATIENTS
SUBMITTED TO FINE NEEDLE ASPIRATION....................................................................................................................... 78
Cristo AP1; Carlucci M1; Blom CB1; Faccin CS1; Goldstein HF1; Maia AL1; Graudenz MS1 PO150 NÓDULO DE TIREOIDE >4 CM: NECESSIDADE DE CITOLOGIA ANTES DE TIREOIDECTOMIA?................................... 78
Pacheco CFV1; Biancardi NF1; Biancardi MF1; Barcelos RN2 PO151 VALOR DIAGNÓSTICO DA PUNÇÃO ASPIRATIVA DA TIREOIDE (PAAF): ESTUDO COMPARATIVO DA
TÉCNICA COM E SEM USO DA ULTRASSONOGRAFIA..................................................................................................... 79
Alcântara-Jones DM; Lavinas-Jones JM; Daltro R; Pitangueira AC; Alcântara FT; Cardeal M; Araújo LMB 1 PO152 HYPOTHYROIDISM FOLLOWING THYROID LOBECTOMY: HOW TO PREDICT?............................................................. 79
Lira RB1; Viana ARO1; De Carvalho AY1; Kowalski LP1
PO153 AVALIAÇÃO DO USO PROLONGADO DO ÁCIDO RETINÓICO NO CARCINOMA AVANÇADO DA TIREOIDE –
ESTUDO FASE II.................................................................................................................................................................... 79
Snaider M1; Mello RCR1; Vaisman M1
PO154 PERSISTENCY OF PAPILLARY THYROID CARCINOMA: MULTIPLICITY AS A PROGNOSTIC FACTOR IN
LOW RISK PATIENTS............................................................................................................................................................ 80
Silva PCA1; Silva MNC2; Colombi AS
PO155 TSH PREQUIRÚRGICA COMO FACTOR PRONÓSTICO (FP) EN EL CÁNCER DIFERENCIADO DE TIROIDES............... 80
Villa S1; Seleme S1; Cabrera S1; Vacchiano V1; Sciorra J1; Rodríguez P1; Corino M1; PO156 EVALUATING THE PROGNOSTIC FACTORS ASSOCIATED WITH CANCER-SPECIFIC SURVIVAL IN WELL
DIFFERENTIATED THYROID CARCINOMA IN PATIENTS > 45 YEARS............................................................................... 80
Quiroa LR1; Goncalves Filho J1; Kowalski LP1
PO157 ANALYSIS OF ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN KINASE (AMPK) SIGNALING IN
DIFFERENTIATED THYROID CARCINOMA BY IMMUNOHISTOCHEMISTRY.................................................................... 80
Vidal APA1; Amdreade BM1; Vaisman F1; Cazarin J1; Pinto LF2; Beitenbach MMD2; Corbo R1; Vaisman1; Caroli-Bottino A1; Carvalho DP1
PO158 EFECTO DE TGF-B1 SOBRE ENZIMAS REDOX Y EN EL CONTROL DEL CICLO CELULAR EN CÉLULAS
TIROIDEAS NORMALES Y TUMORALES............................................................................................................................. 81
Oglio R1; Thomasz L2; Salvarredi L1; Juvenal G2; Pisarev M3 PO159 ROLE OF TOLL LIKE RECEPTOR 4 IN THYROID CARCINOGENESIS INDUCED BY THE ONCOGENE BRAF V600E..... 81
Nazar M1; Peyret V1; Nicola JP1; Pellizas CG1; Masini-Repiso AM1
PO160 BRAF V600E ONCOGENE EXPRESSION AND TLR4 ACTIVATION MODULATE EPIDERMAL GROWTH FACTOR
RECEPTOR (EGFR) IN THYROID TRANSFORMED CELLS................................................................................................. 81
Peyret V1; Nazar M1; Nicola JP1; Pellizas CG1; Masini-Repiso AM1
PO161 TUMOR DE CÉLULAS REDONDAS NA CITOLOGIA TIREOIDIANA: RELATO DE CASO................................................... 82
Sasson P1; Santos JCV 1; Magalhães RSC1; Reis MDSLC 1; Maia CP 1; Mansur VAR 1; Corrêa MV 1; Macedo LRW 1
PO162 YODURIA EN ADULTOS SANOS........................................................................................................................................... 82
Flores-Rebollar A1; Lendechy-Velázquez M1; Castro-Sánchez A1; López-Carrasco G1; Estrada-Joe LI1; Ruiz-Juvera A1;
Martínez C2; González-Treviño O1 PO163 VALORES DE REFERENCIA DEL VOLUMEN TIROIDEO EN ADULTOS, DETERMINADO POR ULTRASONOGRAFÍA..... 82
Flores-Rebollar A1; Castro-Sánchez A1; López-Carrasco G1; Kanan-Falcón M1; Ruiz-Juvera A1; González-Treviño O1 10
Sumário
PO164 THYROGLOBULIN IS A SENSITIVE MEASURE OF BOTH DEFICIENT AND EXCESS IODINE INTAKES IN
CHILDREN AND INDICATES NO ADVERSE EFFECTS ON THYROID FUNCTION IN THE UIC RANGE OF
100-299 mG/L. STUDY OF PARAGUAY COMPARING WITH OTHER COUNTRIES............................................................ 83
Jara Yorg JA; Zimmerman MB; Aeberli I; Anderson MI; Timmer A; Pretell E; Jara MA; Jara Ruiz JM; Jara Ruiz ED; Benitez D1
PO165 URINARY IODINE CONCENTRATION AND THYROID VOLUME IN OVERWEIGHT AND OBESE
SCHOOLCHILDREN IN QUERETARO CITY, MEXICO.......................................................................................................... 83
Méndez-Villa L1; Sampson-Zaldívar E2; Robles-Osorio L1; Solís-S JC1; García-Solís P1
PO166 ASSESSMENT OF IODINE NUTRITION AND THYROID FUNCTION IN MEXICAN WOMEN OF
REPRODUCTIVE AGE........................................................................................................................................................... 83
Méndez-Villa L1; Elton-Puente JE2; Sampson-Zaldívar E3; García-Gutiérrez C4; Villalobos P5; Robles-Osorio L4; Solís-S JC4;
Colarossi A6; García OP2; García-Solís P4
PO167 AVALIAÇÃO DA ANÁLISE COMBINADA DAS CARACTERÍSTICAS ULTRASSONOGRÁFICAS E CITOLÓGICAS
DE NÓDULOS TIREOIDIANOS NA DIFERENCIAÇÃO DE NÓDULOS BENIGNOS E MALIGNOS...................................... 83
Liberati APT1; Tomimori EK1; Silva ES2; Marui S1; Camargo RY1
PO168 THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS: CASE REPORT............................................................................ 84
Colombo BS1; Silva MC1; Canalli MHBS1; Colombo G1
PO169 THE INFLUENCE OF SUBCLINICAL HYPOTHYROIDISM IN DEPRESSIVE SYMPTOMS AND COGNITIVE
IMPAIRMENT OF ELDERLY SUBJECTS FROM A TERTIARY HOSPITAL........................................................................... 84
Chan IT1; Sial J1; Leu A1; Paixão Jr CM2; Vaisman M1; Silva SO1; Teixeira PFS1
PO170 TIROIDITIS DE HASHIMOTO ASOCIADO A POLINEUROPATÍA IDIOPÁTICA DESMIELINIZANTE CRÓNICA (CIDP)...... 84
Jiménez M1; Jiménez P1; Toledo V1; Iturrieta V1
PO171 MANIFESTACIONES TIROIDEAS EN EL SÍNDROME HAMARTOMATOSO TUMORAL DEL PTEN................................... 85
Faure EN1; Pastorino Casas V1; Garuti R2; Tosti R1; Lutfi RJ3 PO172 RELACIÓN DE AUTOINMUNIDAD TIROIDEA Y CARCINOMA DIFERENCIADO DE TIROIDES......................................... 85
Rivadeneira S1; Gutnisky L1; Viale F1; Olstein G1; Colobraro A1; Gauna A1 PO173 PERCUTANEOUS LASER ABLATION IN BENIGN THYROID NODULES: FIRST BRAZILIAN EXPERIENCE..................... 85
Andreoni DM1; Garcia RG2; Janovsky CPS1; Mendes GF2; Ikejiri ES1; Lucio JFF2; Hidal JT1; Francisco Neto MJ2; Maciel RMB1 PO174 DOENÇAS DA TIREOIDE: UM ALERTA CONTRA A NEGLIGÊNCIA NA PREVENÇÃO, NO ACOMPANHAMENTO
E NO TRATAMENTO DAS AFECÇÕES PREVALENTES....................................................................................................... 86
Torres FF1; Brasileiro ES2; Arruda CCC2; Silva KF2; Leite DSA2; Bezerra CSM2; Cruz NA2; Sampaio RAAF2; Guedes LSM2;
Filho PCM2; Façanha CFS3; Forti AC2
PO175 PREVALENCIA DE BOCIO Y SU RELACIÓN CON PARÁMETROS BIOQUÍMICOS EN PACIENTES
ACROMEGÁLICOS................................................................................................................................................................ 86
Alfieri A1; Giacoia E1; Cabrera S2; Magat P2; Moratto E2; Corino M2 PO176 ACUTE SUPURATIVE THYROIDITIS BY E. COLI: A CASE REPORT................................................................................... 86
Noriega VH1; Huachin MK1; Jara J1; Baca R1 PO177 INGESTÃO CRÔNICA DE CANELA REGULA A EXPRESSÃO DE GENES ENVOLVIDOS NO METABOLISMO
DE COLESTEROL EM RATOS HIPOTIREÓIDEOS............................................................................................................... 87
Lopes BP1; Gaique TG2; Souza LL1; Paula GSM1; Pazos-Moura CC1; Oliveira KJ2
PO178 DIPHENYL DISELENIDE REGULATES EXPRESSION OF ANTIOXIDANT GENES IN METHIMAZOLE-INDUCED
HYPOTHYROID FEMALE RATS............................................................................................................................................ 87
Dias GRM1; Golombieski R1; Nogueira CW1; Vargas NBV1 PO179 ANTIDEPRESSANT-LIKE EFFECT OF DIPHENYL DISELENIDE SUPPLEMENTATION IN THE EXPERIMENTAL
HYPOTHYROIDISM INDUCED BY METHIMAZOLE............................................................................................................. 87
Dias GRM1; Almeida TM1; Nogueira CW1; Barbosa NBV1
PO180 DIPHENYL DISELENIDE SUPPLEMENTATION AFFECTS BIOCHEMICAL PARAMETERS IN THE EXPERIMENTAL
HYPOTHYROIDISM INDUCED BY METHIMAZOLE............................................................................................................. 88
Dias GRM1; Dobrachinski F1; Bridi JC1; Portella R 1; Carvalho NR1; Nogueira CW1; Barbosa NBV1 PO181 EXPRESSION OF CASPASES AND BCL-2 FAMILY GENES UNDER HYPOTHYROIDISM: MODULATION BY
DIETARY DIPHENYL DISELENIDE........................................................................................................................................ 88
Dias GRM1; Golombieski R1; Nogueira CW1; Barbosa NBV1
PO182 TSH NEONATAL A LO LARGO DE 10 AÑOS DE PESQUISA DE HIPOTIROIDISMO CONGÉNITO EN UN
HOSPITAL DE LA CIUDAD DE BUENOS AIRES: VARIACIONES DE UN INDICADOR DE DEFICENCIA DE IODO........... 88
Junco M1; Odriozola A1; López M1; Silva Croome MC1; Gauna A1; Glikman P1 11
Sumário
PO183 THYROID AUTOIMMUNITY IN THE CURRENT IODINE ENVIRONMENT IN CHILDREN AND ADOLESCENTS
IN SÃO PAULO, BRAZIL........................................................................................................................................................ 89
Miranda DMC1; Masson JN1; Tomimori EK1; Monte O1; Catarino RM2; Santos RTM2; Toyoda S3; Marone MMS3
PO184 NORMATIZAÇÃO DA VOLUMETRIA SONOGRÁFICA DA GLÂNDULA TIREOIDE NO PERÍODO NEONATAL.................. 89
Freire R1; Monte O1; Catarino RM2; Mattos Jr HS3; Fagundes LB3; Santos LWR3; Sterza T4; Liberato MM3; Pereira KCC4; Rocha T4;
Pereira A5; Cintra T5; Hegner C5; Lube D5; Murad M6; Casini AF6; Tomimori EK1
PO185 FUNCTIONAL CHARACTERIZATION OF HUMAN ECTOPIC THYROID TISSUE WITH IMMUNOHISTOCHEMISTRY...... 89
Camargo RY1; Kanamura CT2; Sodre AK1; Nogueira CR3; Cerutti JM4; Iosrcansky S5; Friguglietti CU6; Tincani AJ7; Medeiros-Neto G1;
Rubio IGS8
PO186 TRATAMIENTO INADECUADO DE LA ENFERMEDAD DE GRAVES DURANTE EL EMBARAZO. HIPOTIROIDISMO
CENTRAL: REPERCUSIÓN FETAL Y NEONATAL POCO DIFUNDIDA................................................................................. 90
Alcaraz G1; Stivel M1; Abalovich M1; Vázquez A1; Calabrese C1; Gutiérrez S1
PO187 CLINICAL ASPECTS OF FAMILIAL FORMS OF CONGENITAL HYPOTHYROIDISM.......................................................... 90
Jesus MS1; Oliveira TL2; Strappa GBS1; Pereira MMA1; Bello AA3; Fernandes VM1; Boa Sorte TRSA3; Ramos HE1 PO188 REPERCUSSIONS OF TSH CUTOFF LEVEL TO 6 MU/L IN NEONATAL SCREENING FOR CONGENITAL
HYPOTHYROIDISM IN SANTA CATARINA: PRELIMINARY RESULTS................................................................................ 90
Nascimento ML1; Dornbusch P2; Ohira M2; Simoni G1; Cechinel E1; Linhares RMM1; Silva PCA1
PO189 DISCORDANCE OF TWINS FOR CONGENITAL HYPOTHYROIDISM IN 3 OF 4 IDENTIFIED PAIRS:
IMPLICATIONS FOR NONINHERITABLE POSTZYGOTIC EVENTS..................................................................................... 90
Strappa GBS1; Oliveira TL2; Jesus MS1; Pereira MMA1; Medeiros MFS1; Boa Sorte TRSA3; Ramos HE1
PO190 FOLLOW-UP OF CHILDREN WITH TSH BETWEEN 5 AND 10 MIU/L ON THE NEWBORN SCREENING TEST:
PRELIMINARY RESULTS...................................................................................................................................................... 91
Christensen FC1; Sewaybricker LE1; Mendes-dos-Santos CT1; Goto MMF1; Gabetta CS1; D’Souza-Li L1; Guerra-Junior G1;
Lemos-Marini SHV1
PO191 EVOLUÇÃO CLÍNICA DO HIPOTIREOIDISMO SUBCLÍNICO EM CRIANÇAS E ADOLESCENTES................................... 91
Villagelin D1; Santos RB1; Cunha MP1; Romaldini JH1
PO192 THIMEROSAL INHIBITS IODOTHYRONINE DEIODINASE ACTIVITY.................................................................................. 91
Pantaleão TU1; Padron AS1; Ferreira ACF1; Carvalho DP1; Rosenthal D1; Correa da Costa VM1
PO193 EFEITO DA INGESTÃO CRÔNICA DE CINAMALDEÍDO SOBRE A FUNÇÃO TIREOIDEANA DE RATOS
SAUDÁVEIS........................................................................................................................................................................... 92
Gaique TG1; Bento-Bernardes T1; Medeiros RF1; Pereira-Toste F1; Oliveira KJ1 PO194 UP-REGULATION OF ADIPONECTIN MRNA BY INDIRECTLY ACTION OF TRIIODOTYRONINE IN
ADIPOCYTES, 3T3-L1........................................................................................................................................................... 92
Oliveira M1; Olimpio RMC1; Sibio MT1; Luvizotto RAM1; Costa LPL1; Conde SJ1; Moretto FCF1; N C R1 PO195 THYROID HORMONE TRANSPORT AND METABOLISM IN MICE DENDRITIC CELLS: EXPRESSION OF
GENES INVOLVED................................................................................................................................................................. 92
Gigena N1; Alamino VA1; Montesinos MM1; Nazar M1; Masini-Repiso AM1; Cremaschi GA2; Pellizas CG1
OR01 TISSUE-SPECIFIC REGULATION OF TRANSPORTERS MCT8 AND MCT10 MRNA BY THYROID HORMONES............. 93
Pereira GF1; Almeida HN1; Império GE1; Bargi-Souza P2; Faustino LC1; Santiago LA1; Nunes MT2; Ortiga-Carvalho TM1
OR02 NONTHYROIDAL ILLNESS SYNDROME ALTERS EXPRESSION OF GENES INVOLVED IN TRANSPORT
AND ACTION OF THYROID HORMONES............................................................................................................................. 93
Cabanelas A1; Fontes KN1; Ramos MBA1; Silva PL1; Pazos-Moura CC1; Rocco PR1; Ortiga-Carvalho TM1
OR03 CARDIAC HYPERTROPHY MEDIATED BY THYROID HORMONE RECEPTOR-B: POSSIBLE ROLES
OF MIRNA-208....................................................................................................................................................................... 93
Império GE1; Pereira GF1; Ramos IPGF1; Santiago LA1; Almeida NAS2; Fuziwara CS3; Kimura ET3; Olivares EL2; Ortiga-Carvalho TM1 OR04 DENDRITIC CELLS (DC) MATURED WITH TRIIODOTHYRONINE (T3) IN THE PRESENCE OF TUMOR
ANTIGENS INDUCE A POTENT ANTITUMORAL RESPONSE: ROLE OF T3 AS ADJUVANT IN DC-BASED
CANCER VACCINES.............................................................................................................................................................. 94
Alamino VA1; Gigena N1; Montesinos MM1; Donadio AC1; Milotich SI2; Masini-Repiso AM1; Rabinovich GA3; Pellizas CG1
OR05 THYROID HORMONES MAINTAIN THE PROLIFERATIVE PHENOTYPE IN T CELL LYMPHOMAS THROUGH
NUCLEAR AND MEMBRANE-INITIATED TRANSCRIPTIONAL PROGRAMS..................................................................... 94
Cayrol F1; Fernando T2; Díaz Flaqué MC1; Genaro AM3; Farías R4; Cremaschi G1; Cerchietti L2
OR06 MATERNAL TYPE 2 DEIODINASE THR92ALA POLYMORPHISM IS ASSOCIATED WITH REDUCED PLACENTAL
ENZYME ACTIVITY BUT DOES NOT SEEM TO BE ASSOCIATED WITH OFFSPRING THYROID DYSFUNCTION........... 94
Dora JM1; Costa JD1; Ribeiro RVP1; Wajner S1; Leiria L1; Da Silva A1; Crispim D1; Maia AL1
12
Sumário
OR07 ELEVATED MATERNAL SUBCLINICAL HYPOTHYROIDISM COULD BE RELATED TO BODY MASS INDEX................... 95
Martínez AC1; Mosso L1; Rojas MP1; Margozzini P2; Solari S1; Lyng T1; Ortiz JA1; Carvajal J1
OR08 CARDIOVASCULAR RISK IN HYPOTHYROIDISM............................................................................................................... 95
Hissa MRN1; Hissa PNG1; Magalhães RA1; Hissa MN1 OR09 EFFECT OF N-ACETYLCYSTEINE ON SERUM THYROID HORMONE LEVELS IN THE ACUTE NONTHYROIDAL
ILLNESS SYNDROME........................................................................................................................................................... 95
Vidart J1; Wajner SM1; Schaan BD1; Maia AL1
OR10 EVALUATION OF BONE AND MINERAL METABOLISM IN PATIENTS WITH THE SYNDROME OF RESISTANCE
TO THYROID HORMONE...................................................................................................................................................... 96
Cardoso LF1; De Paula FJA1; Maciel LMZ1
OR11 PAX8 AND P65 ARE INVOLVED IN THE REDUCED TRANSCRIPTION RATE OF SODIUM-IODIDE
SYMPORTER (NIS) INDUCED BY IODIDE EXCESS............................................................................................................. 96
Serrano-Nascimento C1; Nicola JP2; Masini-Repiso AM2; Nunes MT1
OR12 TRANSCRIPTION FACTOR NKX2.5 UPREGULATES H2O2 GENERATION AND INHIBITS IODIDE UPTAKE
IN PCCL3 CELLS................................................................................................................................................................... 96
Penha RCC1; Santos MCS1; Cardoso LC2; Carvalho DP1; Ferreira ACF1
OR13 LYSOSOMAL DEGRADATION AND CLATHRIN-MEDIATED ENDOCYTOSIS ARE INVOLVED IN IODIDE-INDUCED
REDUCTION OF NIS EXPRESSION AND ACTIVITY............................................................................................................. 97
Serrano-Nascimento C1; Nicola JP2; Calil-Silveira J1; Masini-Repiso AM2; Nunes MT1
OR14 HYPOTHALAMUS-PITUITARY-THYROID AXIS IN PERINATALLY EXPOSED RATS CAN BE DISRUPTED
BY A LARGELY-USED BROAD-SPECTRUM HERBICIDE – GLYPHOSATE......................................................................... 97
Kizys MML1; Sena-Souza J1; Romano RM1; Frossard MM1; Ortiga-Carvalho TM2; Maciel RMB1; Giannocco G3; Dias-da-Silva MR1;
Romano MA4; Chiamolera MI5 OR15 HYPOTHYROIDISM DURING PREGNANCY INCREASES THE SEVERITY OF EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS IN THEIR ADULT OFFSPRING....................................................................................................... 97
Albornoz EA1; Gonzalez PA1; Riveros T2; Cortes C3; Opazo MC1; Carreño LJ2; Bueno SM2; Kalergis AM2; Riedel CA1 OR16 UNEXPECTED HIGH LEVEL OF CALCITONIN IN PATIENTS WITH APPARENTLY CURED MEDULLARY THYROID
CARCINOMA: A NOVEL PITFALL IN THE IMMUNOASSAY – THE “MACROCALCITONIN”............................................... 98
Alves TG1; Kasamatsu TS1; Yang JH1; Lindsey SC1; Camacho CP1; Furuzawa GK1; Kunii IS1; Chiamolera MI1; Maciel RMB1;
Vieira JGH1; Dias da Silva MR1; Martins JRM1 OR17 ARE ECHOGRAPHIC FEATURES RELEVANT IN THE DIAGNOSIS OF MALIGNANT THYROID NODULES
IN ELDERLY PATIENTS?........................................................................................................................................................ 98
Vera MI1; Meroño T1; Parisi C1; Urrutia A1; Cejas C1; Schnitman M1; Zuk C1; De Barrio G1; Silveira R1; Morosan Y1; Rosmarin M1;
Serrano MS1; Serrano L1; Luciani W 1; Faingold MC1; Brenta G1
OR18 THYROTOXICOSIS DUE TO INCREASED CONVERSION OF THYROXINE TO TRIIIODOTHYRONINE IN A
PATIENT WITH LARGE METASTASES OF FOLLICULAR THYROID CARCINOMA TREATED WITH SORAFENIB............ 98
Liberati APT1; Dias EO1; De Castro G Jr2; Danilovick DS1; Hoff A2; Camargo RYA1
OR19 CTLA-4 GENETIC PROFILE OF RISK FOR GRAVES DISEASE IN THE IN BRAZILIAN POPULATION.............................. 99
Bufalo NE1; Rocha AG1; Secolin R1; PiaiRP1; Santos RB2; Romaldini JH2; Ward LS1
OR20 THYROID VOLUME, POSITIVE TRAB, AND THYROTOXICOSIS SYMPTOMS ARE RISK FACTORS ASSOCIATED
WITH THE NATURAL COURSE OF ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM................................................ 99
Godi AC1; Nogueira CR2; Vilar HC1; Sgarbi JA1 OR21 THE TYPE 3 DEIODINASE DISPLAYS HIGH CATALYTIC EFFICIENCY IN THYROID HORMONE INACTIVATION
UNDER PHYSIOLOGICAL OR PHYSIOPATHOLOGICAL CONDITIONS.............................................................................. 99
Wajner SM1; Rohenkohl HC1; Maia AL1 OR22 SELENIUM PARTIALLY REDUCES THE EFFECT OF OXIDATIVE STRESS MEDIATED BY INTERLEUKIN-6
ON THE TYPE 3 DEIODINASE............................................................................................................................................ 100
Rohenkohl HC1; Maia AL1; Wajner SM1 OR23 IODINE BLOCKS SMAD4 INHIBITION BY MIR-19 AND RESTORES TGFB RESPONSIVENESS DURING BRAF
ONCOGENE ACTIVATION IN THYROID CELLS.................................................................................................................. 100
Fuziwara CS1; Kimura ET1
OR24 POTENTIAL ANTI-TUMORIGENIC EFFECTS OF AMP- KINASE (AMPK) ON PAPILLARY THYROID TUMOR
CELL LINEAGES.................................................................................................................................................................. 100
OR25 ADIPONECTIN, LEPTIN, RESISTIN AND GHRELIN: IN SEARCH OF THE LINKS BETWEEN OBESITY
AND DIFFERENTIATED THYROID CANCER...................................................................................................................... 101
Batista FA1; Marcello MA1; Almeida JFM1; Cavalari C1; Rocha AG1; Cunha LL1; Assumpção LVM1; Carvalho AL2; Ward LS1
13
Sumário
OR26 GENOME-WIDE COPY NUMBER ANALYSIS IN A FAMILY WITH P.G533C RET MUTATION AND MEDULLARY
THYROID CARCINOMA IDENTIFIED REGIONS ASSOCIATED WITH HIGHER PREDISPOSITION TO
LYMPH NODE METASTASIS............................................................................................................................................... 101
Araujo AN1; Moraes LS1; França MIC1; Maciel RMB1; Cerutti JM1
OR27 PROGNOSTIC VALUE OF GROWTH FACTOR SIMILAR TO INSULIN 1 (IGF-1) AND IGF-1 RECEPTOR (IGF-1R)
IN DIFFERENTIATED THYROID CARCINOMA (DTC) WITH ENPHASIS ON LOW-RISK PAPILLARY
THYROID CARCINOMA....................................................................................................................................................... 101
Dias EO; Basso M; Kanamura C; Galrao AL; Marui S; Camargo RY1 OR28 MIR-106B IS DOWN-REGULATED IN FOLLICULAR CARCINOMAS AND MAY MODULATE C1ORF24
EXPRESSION BY INHIBITING C1ORF24 MRNA AND PROTEIN EXPRESSION............................................................... 102
Nozima BHN1; Carvalheira GMG1; Cerutti JM1 OR29 PRESURGICAL DETECTION OF BRAF V600E MUTATION IN FNAB SPECIMENS AND CORRELATION
WITH AGGRESSIVENESS OF PAPILLARY THYROID CARCINOMA................................................................................. 102
Lima EU1; Tomimori EK2; Camargo RYA2; Domingues RB3; Marui S1 OR30 ALTA FRECUENCIA DE BRAF V600E EN CÁNCER PAPILAR DE TIROIDES, ASOCIACIÓN CON
MARCADORES DE DIFERENCIACIÓN CELULAR Y PARÁMETROS CLÍNICOS E HISTOLÓGICOS............................... 102
Pineda P1; Osorio F1; Lanas A1; Cabané P2; Morales C3; Espinoza J4; Tapia V4 14
Artículo Comentado
Bocios multinodulares mixtos tratados con 131I
e inyecciones de etanol en forma combinada*
Jara Yorga JA

Jara MA

Jara Ruiz JM
Summary
U
ltrasonic examination of the thyroid is important to
make any diagnosis and treatment on the thyroid
nodules. Scintigraphy helps to identify autonomous adenoma and hot nodules in multinodular goiter (MNG) and
to follow up treatment done with 131I .Ultrasound therapies
like percutaneus ethanol and mepivacaine (PEI) instillation
is an effective treatment associated with 131I in MNG.
We present 80 patients with multinodular hyperthyroidism, clinically diagnosed by ultrasonography and thyroid
scintigraphy with Tc99, whom underwent thyroid needle
biopsy under ultrasound screen which were all negative
for atypical cells. They were carriers of mixed nodules, 58
female and 22 male, aged between 18 and 68 years with
an average of 38 years who were seen in CEDIN from
October 2010 to May 2011 and treated with 131I orally, with
an average dose of 25 mCi (925 mBq). All patients achieved an average reduction of 66% (SD 39.28) in the size
of cystic nodules with ethanol plus mepivacaine injection.
The initial volume having an average of 10.80ml. About
87,5%(70) of patients achieved a reduction of 90% in the
size of the nodules . All patients were subjected to a diet
low in iodine ten days before dosing.
Keywords: Multinodular Goiter, ultrasonography,
mepivacaine, ethanol, 131I therapy, Na levothyroxine.
Antecedentes
Un nódulo tiroideo es una lesión con aumento focal
del volumen o de la consistencia localizada dentro de la
glándula tiroides, que se distingue del resto del parénquima1 y puede ser detectado por palpación o por estudios de imágenes, principalmente la ultrasonografía de
alta resolución.
Los exámenes físicos comprueban que los nódulos
se encuentran en la población, predominantemente de
sexo femenino,1 pudiendo estos ser únicos o múltiples.
* CEDIN, Centro de Diagnóstico y Tratamiento Nuclear, Centro Endocrinológico y Diagnóstico por Imagen. Asunción, Paraguay
a
Profesor de Endocrinología y Medicina Nuclear, Cátedra de Patología
Médica, Universidad Nacional de Asunción, Director del Centro de Diagnostico y Tratamiento Nuclear y Centro Endocrinológico y Diagnóstico
por Imagen (CEDIN), Asunción, Paraguay, Representante del ICCIDD en
el Paraguay.
Correspondencia para:
Jorge Antonio Jara Yorg MD
e-mail: [email protected]

Jara Ruiz ED
Los palpables tienen una prevalencia del 4%-7% en las
mujeres y del 1% en los hombres que viven en sitios con
suficiencia de iodo.1,2 Por lo tanto, es posible afirmar que
este segmento representa un problema clínico, puesto
que aparece frecuentemente en la consulta médica. En
los estudios de autopsias de pacientes sin antecedentes de
patología tiroidea, la prevalencia es de alrededor del 49%
pudiendo llegar al 65%.3,4 El ultrasonido puede detectar
del 19%-35% de los nódulos, mientras que la palpación
los detecta en una variación del 2%-6%.5
Entre los criterios utilizados para el manejo de los nódulos benignos y malignos, las sociedades de especialistas en
tiroides recomiendan el examen clínico, el ultrasonido, la
punción biopsia aspirativa con aguja fina y guiada bajo pantalla ecográfica, la gammagrafía de tiroides, el dosaje de las
hormonas tiroideas y de los anticuerpos antitiroideos en sangre, los controles de tiroglobulina sérica, el rastreo corporal
total con 131I, la tomografía computarizada y el PET-CT.
Entre los tratamientos propuestos están la cirugía, el
tratamiento ablativo con el Iodo 131 (131I), el uso de levotiroxina sódica de reemplazo con niveles de supresión. En
el hipertiroidismo se utilizan drogas antitiroideas como el
Metimazol (Danantizol) y el Propil Tio Uracilo (PTU). La
toxicidad del hígado, debido a las tionamidas, es rara de
suceder, pero es más severa debido al PTU. Sin embargo,
se cita también ictericia colestásica y hepatitis aguda
tóxica debido al metimazol y a la reacción cruzada con el
Propiltiouracilo.6 En el 20%-30% de los casos de pacientes
que sufren la enfermedad de Graves, y que son tratados
con drogas antitiroideas en un período de 12-18 meses, el
resultado es una remisión prolongada de la enfermedad.
La suspensión de dichas drogas, una semana antes del
tratamiento con 131I, no interfiere en el curso de la curación y de los efectos del radioyodo.7
La predilección por el uso de la cirugía y del 131I, como
terapias, varía de acuerdo a las regiones y países. El 131I es
utilizado como primera elección8 en la enfermedad de
Graves-Basedow en EEUU, Europa y Japón, en el 69%,
22% y 11%, respectivamente.
Las drogas antitiroideas constituyen la primera elección terapéutica en el 30%, 77% y 89%, respectivamente,
en esos m i s m o s países, mientras que la tiroidectomía
subtotal posee el nivel más bajo como primera elección
(1%) y es mencionada como de elección con unánime
falta de entusiasmo.8
15
Artículo Comentado
El nódulo sometido al tratamiento con 131I tiene un
45% de probabilidad de desaparición y un 68% de disminución de tamaño. Si existe alguna lesión pequeña
(<10mm) con carcinoma, tiene un curso benigno.9,10 El
radioyodo no aumenta la probabilidad de la aparición
de un cáncer tiroideo subsiguiente y no se ha establecido
riesgo teratogénico utilizando este isótopo.11
Se debe considerar la punción tiroidea por aspiración
con aguja fina (PAAF) como un procedimiento confiable
y seguro, así como el mejor método costo-efectivo para
distinguir entre un nódulo tiroideo maligno o benigno.
Su uso ha permitido disminuir el número de intervenciones quirúrgicas en el manejo de la enfermedad tiroidea nodular.12-16La mayoría de los nódulos detectados
clínicamente pueden ser aspirados, siendo el ultrasonido
el mejor método para aumentar la cantidad de material
obtenido para la interpretación citológica.
El uso combinado del ultrasonido y la PAAF puede disminuir el número de muestras inadecuadas a menos del
5%.15 Se recomienda realizarlas en todos los nódulos mayores de 10 mm o en aquellos menores de 10 mm, pero con
datos sugestivos de malignidad. Con el material aspirado
se hace un frotis que se fija con alcohol, se tiñe y es interpretado por el patólogo. La punción se puede realizar fácilmente en el consultorio. La sensibilidad y la especificidad
de la PAAF realizada por médicos experimentados, es del
83% (rango 65-98%) y del 92% (rango 72%-100%), respectivamente. La tasa de falsos negativos es en promedio del
5% (rango 1%-11%) y la de falsos positivos, de < 1%-7%.16
Los bocios multinodulares hiperfuncionantes17,18 que
producen un exceso de hormonas tiroideas e inhiben la
secreción hipofisaria de TSH, frecuentemente precisan de
la gammagrafía tiroidea, la cual no solo es definitiva en el
diagnóstico de la hiperplasia multinodular, sino que además es la exploración que permite confirmar el diagnóstico clínico de sospecha, pues evidencia, en primer lugar, el
aumento de tamaño de la tiroides y, sobre todo, la presencia
de una distribución irregular del trazador en la glándula.
La cirugía en el bocio multinodular representa una
modalidad terapéutica muy utilizada, sin embargo, entre
los tratamientos no invasivos, el 131 I es una de las
opciones y la adición de la inyección intranodular de etanol, 19-21como herramienta terapéutica, ayuda a la mejor
resolución de los nódulos mixtos con áreas quísticas.
Ambas terapias no invasivas pueden repetirse y no presentan contraindicaciones, excepto el 131I en el embarazo
y la lactancia. Pero el etanol ha sido utilizado por años en
patologías benignas,20,21 en nódulos quísticos y en algunos
sólidos como en los nódulos autónomos, y ha sido utilizado en el tratamiento de patologías malignas tiroideas,
como en el carcinoma diferenciado de tiroides.22
El radioyodo ha sido utilizado como una terapia de primera línea en el hipertiroidismo difuso, en el bocio uni
y multinodular, además de ser reconocido como alta-
16
mente efectivo en la cura de la enfermedad de GravesBasedow,23-25 la cual también presenta variedades nodulares, entre las cuales se observa el síndrome de Marine
Lenhart.26,27 Los hallazgos importantes descritos en otros
trabajos, como el sexo masculino, la concentración de
FT4 muy elevada, el tratamiento previo con antitiroideos
y el tamaño mediano o muy grande del bocio, influencian
en la respuesta del 131I, por lo que deben ser tomados en
consideración cuando se planea un tratamiento con radioyodo, ya que las dosis deben ser más elevadas.19-28
La terapia con levotiroxina y levotiroxina más ioduro
de potasio logran la reducción del nódulo tiroideo en un
7,3% y en el 17.3%, respectivamente, en el período de un
año,29 pero se ha demostrado que un nódulo hipercaptante34 sometido al tratamiento con 131I, en la enfermedad
de Graves, tiene una probabilidad de desaparición o de
disminución de tamaño del 68%.
El bocio multinodular observado en la enfermedad de
Graves puede ser tratado por un método no quirúrgico y
obtener un 85% de éxito, incluyendo un 43% de desaparición de los nódulos.30
Los nódulos autónomos en la enfermedad de Graves
(Sx. de Marine-Lenhart) son raros y deben ser tratados con
altas dosis de 131I (25 mCi o 925 mBq), lo cual da un 75% de
éxito en la erradicación del nódulo.31-34 En el tratamiento
de nódulos tiroideos con etanol, la adición, desde el 2008,35
de la mepivacaína como un anestésico que –mezclado al
alcohol logra disminuir el dolor durante y después de la
inyección en los nódulos tiroideos, bajo guianza ecográfica
a los pacientes–, permitió la repetición de las dosis de etanolización en forma múltiple –sin mayores inconvenientes para los pacientes– hasta lograr la desaparición de los
nódulos o su disminución en forma notable.
Objetivos
1. Evaluar la eficacia del tratamiento de los bocios multinodulares mixtos con terapia combinada de 131I por vía
oral, con la adición de inyecciones intranodulares bajo
pantalla ecográfica de etanol + mepivacaína.
2. Comparar el tamaño de los nódulos tiroideos pre y
post terapia combinada, con ambas técnicas.
Material y métodos
Se estudió y se trató a 80 pacientes con diagnóstico de
bocio multinodular tóxico. A estos se les efectuó, previamente, una ecografía tiroidea, un centellograma con captación y una PAAF bajo pantalla ecográfica con citología
benigna. Todos los pacientes que fueron atendidos en el
CEDIN desde octubre de 2010 hasta mayo de 2011, que
fueron tratados con 131I por vía oral, con una dosis promedio de 25 mCi (925 mBq), eran portadores de bocio
multinodular mixto (sólido-quístico): 58(72,5%) de
sexo femenino y 22(27,5%) de sexo masculino, con
Artículo Comentado
una relación 3:1 de mujeres a hombres, y con edades
comprendidas entre 18 y 68 años, siendo el promedio de
38 años. Las gammagrafías tiroideas se realizaron con una
gamma cámara Spect Mediso, utilizando el Pinhole.
Todos los pacientes fueron tratados con inyecciones de
etanol etílico al 98% + mepivacaína al 3% sin epinefrina.
Fueron utilizados filtros de millipore a una dosis calculada al 20% del volumen del nódulo tiroideo observado y
medido bajo pantalla ecográfica, utilizando un ecógrafo
General Electric Vivid E, con un transductor lineal de
5-12 MHz, y fueron realizadas cada tres semanas. Todas
las inyecciones de etanol fueron iniciadas 2 semanas después de la administración del radioyodo.
Todos los pacientes lograron una reducción promedio
del 66% (DE 39,28) del tamaño de los nódulos quísticos con
inyecciones de etanol + mepivacaína, siendo el volumen inicial de los mismos de un promedio de 10,80 mL. El 88% de
los pacientes logró una reducción del tamaño de los nódulos
del 90% utilizando ambos procedimientos. Todos los pacientes fueron sometidos a una dieta de bajo contenido en iodo
diez días antes de la dosis. Ninguno de los pacientes presentó
trastornos graves después del 131I, pero se observó dolor
intratiroideo durante la inyección del etanol + mepivacaína
que fue muy localizado en el sitio de la inyección, de intensidad leve a moderada (aproximadamente 20-80 segundos),
el cual rápidamente se redujo en el 70% de los pacientes. El
30% de los pacientes no presentó ningún dolor durante el
procedimiento. Solo 3 pacientes presentaron disfonía inmediatamente después de la administración del etanol, uno de
ellos por 2 semanas con recuperación total de la voz, otro
por 2 meses y otro durante 24 horas. Todos ellos recuperaron totalmente el timbre y la potencia de la voz. Hipotensión
postetanol se observó en 2 pacientes con una presión arterial
(PA) promedio de 100/65 mm Hg, con rápida normalización.
Todos los demás no presentaron trastornos ni cambios de la
PA. El promedio de inyecciones de los pacientes tratados fue
de tres, con una sola dosis del 131I administrada por vía oral.
Los quistes, de aquellos que tenían, fueron previamente aspirados con la misma aguja.
Tabla 1
Características
Mujeres
N° (%)
58 (80%)
Hombres
Promedio de edad
Dosis promedio de 131I
Promedio de reducción de los nódulos
con etanol
Promedio de reducción de nódulos con
etanol + 131I en el 88% de los pacientes
Número Total de pacientes
Tipo de Tratamiento:
131
I + Etanol
Tiempo de evolución de mejoría de los
nódulos
3 nódulos
4 nódulos
Dosis of etanol
22 (20%)
38
25mCi(925 mBq)
66%
90%
80
80
5 meses
8 meses
Número de
pacientes
64
12
1 cc
2 cc
Nódulos mixtos previos al tratamiento
Resultados
Todos los pacientes lograron reducción del tamaño
tiroideo. El 88% de los pacientes consiguió una reducción
del 90%. El dolor fue muy escaso en el sitio de inyección
y demoró 1 minuto en desaparecer por acción de la mepivacaína. Tres personas presentaron disfonía en un período de 24 a 72 horas, con total recuperación de la voz. El
tratamiento con 131I permite la reducción del 60 al 82%
del volumen de los nódulos hipercaptantes. Sin embargo,
en los nódulos mixtos que presentan áreas quísticas, su
reducción es más limitada, por lo cual con la adición de
inyecciones de etanol + mepivacaína, cada 3 semanas, se
logró una reducción del 66% (DE 39,28), siendo el volumen inicial de los nódulos de un promedio de 10,80 mL.
Después del 131I y la 1a inyección de etanol
17
Artículo Comentado
Después de la 2a inyección de etanol
Nódulo post 2a inyección de etanol
Después de la 3a inyección de etanol
Nódulo tiroideo con inyección de etanol utilizando un
filtro de millipore
Nódulo pre y post etanol
18
Artículo Comentado
A
1a Imagen post 25 mci 131I
Nódulo tiroideo con reducción casi total
B
C
1 mes después
D
E
Tres meses después
Cuatro meses después
2 meses después
F
Cinco meses después
19
Artículo Comentado
Nódulos tiroideos tratados con 131I y etanol muestran reducción total
Discusión
Los nódulos tiroideos pueden ser tratados quirúrgicamente, pero la probabilidad de la destrucción o disminución del tamaño de los mismos, por medios no
invasivos, ha sido durante años objeto de investigación
por muchos tiroidólogos. La aparición, en la década de
los 40, del 131I radioactivo, con Hertz y Roberts, en el
Hospital General de Massachussets, EEUU, para ser
utilizado en la terapia del hipertiroidismo, logró un
inmenso avance en el tratamiento del hipertiroidismo
como también en el tratamiento del cáncer diferenciado
de tiroides y la ablación del remanente hasta nuestros
días. Su utilización posterior en la reducción pre quirúrgica de grandes nódulos tiroideos eufuncionantes y
con la adición de inyecciones con etanol, tanto en patologías benignas o malignas tiroideas, y en el espectro de
terapias combinadas, ha ganado un campo con mucho
éxito en la reducción de los nódulos tiroideos benignos.
Es innegable que el etanol ha sido utilizado no solo en la
patología benigna tiroidea, sino también en la maligna,
para lograr la ablación del remanente que no responde a
la terapia con 131I. 36
Dentro de este espectro, la terapia combinada del 131I
y el etanol, en nuestra experiencia, ha sido muy exitosa,
20
especialmente por la predilección de los pacientes por la
terapia no invasiva luego de descubrir que su patología
nodular es benigna y puede ser tratada no quirúrgicamente con resultados asombrosos. Los pacientes quedan
satisfechos y evitan riesgos quirúrgicos.
Conclusión
Los bocios multinodulares hipercaptantes pueden ser
tratados con la terapia combinada del 131I por vía oral
y por la adición de inyecciones de etanol + mepivacaína
intranodular con reducción del volumen de los nódulos
y con desaparición de otros. Así, los pacientes mejoran y
se evitan posibles cirugías tiroideas.
Referencias
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23. Koroscil TM 1995 Thionamides alter the efficacy of radioiodine treatment in
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Chaparro N., Ovelar A. “Graves’ Disease and Toxic Adenoma Treated with I-131 in Paraguay. Libro Instituto de Investigaciones en Ciencias de la Salud, Tomo II, EDUNA,
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25. Franklyn JA 1994 The management of hyperthyroidism. N Engl J Med 330:
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32. Nortdyke RA, Gilbert EL Jr, Optimal iodine-131 dose for eliminating hyperthyroidism in Grave’s disease. J. Nucl Med 1991; 32:411-6.
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34. (Nuggard B, Hegedus L, Nielsen KG, Ulriksen P, Hansen JM. Long term effect
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35. Painless therapy of the cystic and solid thyroid nodules with injections of ethanol plus mepivacaine under ultrasound guidance, Jara Yorg J.A.,Jara M.A.,Jara Ruiz J.M.
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21
Artículo Comentado
Comentarios sobre las recomendaciones de la guía:
Management of thyroid dysfunction during pregnancy and
pospartum: an endocrine society clinical practice guideline*
Comparación con la guía de la endocrine society del año
2007
Marcos Abalovicha
L
a Endocrine Society acaba de publicar su nueva Guía
para el manejo de las enfermedades tiroideas durante
el embarazo y el post-parto, luego de 5 años de la publicación previa. Tanto en la Guía del 2007 como en la actual,
he tenido el honor y la responsabilidad de representar a la
Sociedad Latinoamericana de Tiroides (LATS).
La nueva Guía mantiene la división en 8 secciones:
Management of Hypothyroidism: maternal and fetal
aspects, Management of hyperthyroidism: maternal and
fetal aspects, Gestational hyperemesis and hyperthyroidism, Autoimmune thyroid disease and miscarriage, Thyroid
nodule and Cancer, Iodine nutrition during pregnancy,
Pospartum thyroidits and Screening for thyroid dysfunction during pregnancy. En la de 2007 se formularon 35
recomendaciones y en la actual 43, habiéndose incrementado particularmente las de la sección de Screening.
Mi intención al realizar esta comparación, es resaltar
las recomendaciones que presentaron modificaciones (los
cambios figuran en negrita) con un pequeño comentario
sobre ellas.
1)MANAGEMENT OF HYPOTHYROIDISM:
MATERNAL AND FETAL ASPECTS
• Se agrega una recomendación más, introduciendo la
posibilidad de utilizar el dosaje de T4 total y del índice
de T4 L, además de la clásica determinación de T4L,
cuyo empleo durante el embarazo ha sido objeto de
controversias. 1.1. We recommend caution in the
interpretation of serum free T4 levels during pregnancy and that each laboratory establish trimesterspecific reference ranges for pregnant women if using
a free T4 assay. The non-pregnant total T4 range (5-12
µg/dL or 50-150 nmol/L) can be adapted in the 2nd and
3rd trimesters by multiplying this range by 1.5-fold.
Alternatively, the free thyroxine index (“adjusted T4”)
appears to be a reliable assay during pregnancy. (USPTF
Recommendation level: B, Evidence-fair) (2|)
* JCEM 97 (8) 2543-2565, 2012
a
Jefe de Tiroides de la División Endocrinología del Hospital Durand, Buenos Aires, Argentina
22
• Se afirma que solo para hipotiroidismo clínico existen
claras evidencias de repercusión sobre madre y feto.
1.2.1. Overt maternal hypothyroidism is known to
have serious adverse effects on the fetus. Therefore
maternal hypothyroidism should be avoided. For overt
hypothyroidism: (USPSTF Recommendation level: A,
Evidence-good) (1|)
• Para el tratamiento del hipotiroidismo subclínico, la
Guía 2012 introduce la diferencia entre tener aTPO+ o aTPO-. Si bien en ambas situaciones se acepta la
posibilidad de tratamiento, la fuerza de la recomendación es diferente. 1.2.2. Subclinical hypothyroidism
(SCH, serum TSH concentration above the upper limit
of the trimester-specific reference range with a normal
free T4) may be associated with an adverse outcome
for both the mother and offspring, as documented in
antibody-positive women. In retrospective studies
thyroxine treatment improved obstetrical outcome, but
it has not been proved to modify long-term neurological development in the offspring. However, given that
the potential benefits outweigh the potential risks, the
panel recommends thyroxine replacement in women
with SCH who are thyroid peroxidase antibody positive (TPOAb+). For obstetrical outcome: (USPSTF
Recommendation level: B, Evidence-fair) (2|);
for neurological outcome: (USPSTF Recommendation level: I, Evidence-poor) (2|). The panel
also recommended T4 replacement in women with
SCH who are TPOAb negative (TPOAb-). For obstetrical outcome: (USPSTF Recommendation level: C,
Evidence-fair) (2|); for neurological outcome:
(USPSTF Recommendation level: I, Evidence-poor)
• Respecto al hipotiroidismo que fue diagnosticado
previo al embarazo, cambia la fuerza de la recomendación (era I y ahora C). A diferencia de la guía de la
ATA 2011, esta Guía no tiene en cuenta buscar valores
de preconcepción menores a 1.2 mUI/L para reducir
las posibilidades de tener que incrementar la dosis de
LT4 durante el embarazo. 1.2.3. If hypothyroidism
has been diagnosed before pregnancy, we recommend
Artículo Comentado
adjustment of the pre-conception thyroxine dose to
reach prior to pregnancy a TSH level not higher than
2.5 mIU/L. (USPSTF Recommendation level: C, Evidence-poor) (2|)
• Tanto en lo que hace al hipotiroidismo, como a la
autoinmunidad tiroidea, diagnosticados durante el
embarazo, la Guía 2012 agrega el plazo de 4 a 6 semanas para el monitoreo de la función tiroidea a lo largo
de la gestación: 1.2.5. If overt hypothyroidism is diagnosed during pregnancy, thyroid function tests should
be normalized as rapidly as possible. Thyroxine dosage
should be titrated to rapidly reach and thereafter maintain serum TSH concentrations less than 2.5 mIU/L in
the 1st trimester (or 3 mIU/L in 2nd and 3rd trimester)
or to trimester-specific TSH ranges. Thyroid function
tests should be remeasured within 30-40 days and then
every 4-6 weeks (USPSTF Recommendation level: A,
Evidence-good) (1|). 1.2.6. Women with thyroid autoimmunity who are euthyroid in the early
stages of pregnancy are at risk of developing hypothyroidism and should be monitored every 4-6 weeks
for elevation of TSH above the normal range for pregnancy. (USPSTF Recommendation level: A, Evidencefair) (1|)
• Respecto al post-parto, agrega que la dosis de LT4
debería reducirse a aquellas de la preconcepción:
1.2.7. After delivery, most hypothyroid women
need to decrease the thyroxine dosage they received during pregnancy to the pre-pregnancy dose.
(USPSTF Recommendation level: A, Evidence-good)
(1|)
2a)MANAGEMENT OF HYPERTHYROIDISM:
MATERNAL ASPECTS
• En la diferenciación entre Enfermedad de Graves e
Hiperémesis Gravídica, jerarquiza la Guía 2012 al
TRAb vs TPOAb: 2.1.1. If a subnormal serum TSH
concentration is detected during gestation, hyperthyroidism must be distinguished from both normal
physiology of pregnancy and gestational thyrotoxicosis
because of the adverse effects of overt hyperthyroidism
on the mother and fetus. Differentiation of Graves’
disease from gestational thyrotoxicosis is supported
by presence of clinical evidence of autoimmunity, a
typical goiter, and presence of thyrotropin receptor
antibodies (TRAb).TPO-Ab may be present in either
case. (USPSTF Recommendation level: B, Evidencefair) (1|)
• En lo que hace al objetivo del tratamiento con drogas
antitiroideas, además de mencionar el mantener a T4
Libre en el rango superior de la no embarazada (aunque baja la fuerza de la recomendación a B), agrega la
posibilidad de usar la T4 total o el índice de T4 Libre.
2.1.2. For overt hyperthyroidism due to Graves’ dis-
ease or thyroid nodules, antithyroid drug therapy
should be either initiated (for those with new diagnoses) or adjusted (for those with a prior history) to
maintain the maternal thyroid hormone levels for free
T4 at the upper limit of the non-pregnant reference
range (USPSTF Recommendation level: B, Evidencefair) (1|) or maintaining total T4 at 1.5 times
the upper limit of the normal reference range or the
free thyroxine index in the upper limit of the normal
reference range. (USPSTF Recommendation level: I,
Evidence-poor) (2|)
• Respecto de la elección del antitiroideo, la Guía 2012
reafirma la elección del PTU en el primer trimestre, pero sugiere la posibilidad de cambiar a MMI en
el resto del embarazo, dando las equivalencias entre
una y otra droga. Advierte también sobre la toxicidad hepática del PTU: 2.1.3. Propylthiouracil (PTU),
if available, has been recommended as the first-line
drug for treatment of hyperthyroidism during the 1st
trimester of pregnancy because of the possible association of methimazole (MMI) with congenital abnormalities that occur during 1st trimester organogenesis.
MMI may also be prescribed if PTU is not available
or if the patient cannot tolerate or has an adverse
response to PTU. MMI 10 mg is considered to be
approximately equal to 100-150 mg of PTU. Recent
analyses reported by Food and Drug Administration
(FDA) indicate that PTU may rarely be associated
with severe liver toxicity. For this reason we recommend that clinicians change treatment of patients
from PTU to MMI after the completion of the 1st trimester. Available data indicate that MMI and PTU
are equally efficacious in the treatment of pregnant
women. Practitioners should use their clinical judgement in choosing the androgen deprivation therapy
(ADT) including the potential difficulties involved
in switching patients from one drug to another. If
switched from PTU to MMI thyroid function should
be assessed after 2 weeks and then at 2 to 4 weeks
Intervals. (USPSTF Recommendation level: B, Evidence-fair) (1|) Although liver toxicity may
appear abruptly, it is reasonable to monitor liver
function in pregnant women on PTU and to encourage patients to promptly report any new symptoms. (USPSTF Recommendation level: C, Evidence-poor)
(2|)
• Respecto de la Cirugía, la Guía 2012 agrega las dosis de
MMi o PTU por encima de las cuales, en caso de ser
persistentes, podría evaluarse la posibilidad de tiroidectomía subtotal. 2.1.4. Subtotal thyroidectomy may
be indicated during pregnancy as therapy for maternal
Graves’ disease if (i) a patient has a severe adverse reaction to antithyroid drug (ATD) therapy, (ii) persistently
high doses of ATD are required (over 30 mg/d of MMI
23
Artículo Comentado
or 450 mg/d of PTU), or (iii) a patient is non-adherent
to ATD therapy and has uncontrolled hyperthyroidism. The optimal timing of surgery is in the second trimester. (USPSTF Recommendation level C, Evidencefair) (2|)
2b) MANAGEMENT OF HYPERTHYROIDISM:
FETAL ASPECTS
• La Guía 2012 sugiere el momento del embarazo en el
cual habría que solicitar TRAb y, además, amplía los
grupos de mujeres a los cuales habría que solicitárselo.
A pesar de que “antes de la semana 22” parece demasiado vago, la intención es que el endocrinólogo disponga de un valor de TRAb inmediatamente antes, o
al momento en que los anticuerpos pasan activamente
a través de la placenta, lo cual ocurre alrededor de las
semanas 18-22. 2.2.1. Since thyroid receptor antibodies (thyroid receptor stimulating, binding, or inhibiting
antibodies) freely cross the placenta and can stimulate
the fetal thyroid, these antibodies should be measured
before 22 weeks of gestational age in mothers with 1)
current Graves’ disease or 2) a history of Graves’ disease and treatment with 131-I or thyroidectomy before
pregnancy or 3) a previous neonate with Graves’ disease or 4) previously elevated TRAb. Women who
have a negative TRAb and do not require ATD have a
very low risk of fetal or neonatal thyroid dysfunction.
(USPSTF Recommendation level: B, Evidence-fair)
(1|)
• La Guía 2012 sugiere el período del embarazo en el
que habría que solicitar Ecografía fetal para evaluar la
posibilidad de disfunción tiroidea fetal, y cada cuánto
tiempo repetirla. Asimismo, sugiere que la madre
reciba antitiroideos, en caso de que se presuma hipertiroidismo fetal: 2.2.3. In women with TRAb or TSI
elevated at least 2- to 3-fold the normal level and in
women treated with ATD, fetal thyroid dysfunction
should be screened for during the fetal anatomy and
ultrasound done in the 18th-22nd week and repeated
every 4-6 weeks or as clinically indicated. Evidence
of fetal thyroid dysfunction could include thyroid
enlargement, growth restriction, hydrops, presence of
goiter, advanced bone age, tachycardia or cardiac failure. If fetal hyperthyroidism is diagnosed and thought
to endanger pregnancy, treatment using MMI or PTU
should be given with frequent clinical, laboratory and
ultrasound monitoring. (USPSTF Recommendation
level: B, Evidence-fair) (1|)
• La Guía 2012 también indica a qué recién nacidos de
madres con Enfermedad de Graves no sería necesario
evaluar: 2.2.5. All newborns of mothers with Graves’
disease (except those with negative TRAb and not
requiring ATD) should be evaluated by a medical care
provider for thyroid dysfunction and treated if neces-
24
sary. (USPSTF Recommendation level: B, Evidencefair) (1|)
3. GESTATIONAL HYPEREMESIS AND
HYPERTHYROIDISM
La Guía 2012 indica que la mera existencia de clínica
de hipertiroidismo, con TSH inhibida y T4 L elevada, no
amerita tratamiento con drogas antitiroideas en mujeres
con hiperémesis gravídica. En aquellas con clínica significativa, elevada T4L, elevación de T3 y/o TRAb positivo,
está la posibilidad de utilizar beta bloqueantes (sugiere
metoprolol) y antitiroideos por posible Enfermedad de
Graves asociada. 3.2. Most women with hyperemesis
gravidarum, clinical hyperthyroidism, suppressed TSH
and elevated FT4 do not require ATD treatment. (USPSTF
recommendation level: A; Evidence-good) (1|)
Clinical judgment should be followed in women who
appear significantly thyrotoxic or who have in addition
serum TT3 values above the reference range for pregnancy. Beta blockers such as metoprolol may be helpful
and may be used with obstetrical agreement. (USPSTF
recommendation level: B; evidence-poor) (2|).
3.3. Women with hyperemesis gravidarum and diagnosed
to have Graves’ hyperthyroidism (free T4 above the reference range or total T4>150% of top normal pregnancy
value, TSH<0.01 µIU/L and presence of TRAb) will
require ATD treatment as clinically necessary. (USPSTF
recommendation level: A; evidence-good) (1|)
4)AUTOIMMUNE THYROID DISEASE
AND MISCARRIAGE
La Guía mantiene el concepto de no indicar tratamiento a la mujer abortadora eutiroidea, aunque tenga
anticuerpos antitiroideos positivos. Pero hace una aclaración acerca del tratamiento que aplicó con LT4 a dichas
pacientes y de lo que debería hacerse con ellas. 4.1. A
positive association exists between the presence of thyroid antibodies and pregnancy loss. Universal screening
for anti-thyroid antibodies and possible treatment cannot be recommended at this time. As of January 2011,
only 1 randomized interventional trial has suggested a
decrease in the 1st trimester miscarriage rate in euthyroid antibody-positive women, but treatment duration
was very brief before the outcome of interest. However,
since women with elevated anti-TPO antibodies are at
increased risk for progression of hypothyroidism, if
identified, such women should be screened for serum
TSH abnormalities before pregnancy, as well as during
the first and second trimesters of pregnancy. (USPSTF
Recommendation level: C, Evidence-fair) (2|)
5)THYROID NODULES
• La Guía 2012 hace una consideración más amplia de
los nódulos que deben punzarse: 5.1. Fine needle aspi-
Artículo Comentado
ration (FNA) cytology should be performed for predominantly solid thyroid nodules >1 cm discovered in
pregnancy. Women with nodules 5 mm-1 cm in size
should be considered for FNA if they have a high
risk history or suspicious findings on ultrasound
and women with complex nodules 1.5-2 cm should
also receive an FNA. During the last weeks of pregnancy, FNA can reasonably be delayed until after
delivery. Ultrasound-guided FNA is likely to have
an advantage for maximizing adequate sampling.
(1|)
• Se indica cuánto tiempo luego de suspendida la lactancia puede indicarse una dosis de Iodo 131. 5.4. Radioactive iodine (RAI) with 131-I should not be given
to women who are breastfeeding or for at least 4 wk
after nursing has ceased. (USPSTF Recommendation
level: A, Evidence-good) (1|) Furthermore,
pregnancy should be avoided for 6 months to 1 year
in women with thyroid cancer who receive therapeutic
RAI doses to ensure stability of thyroid function and
confirm remission of thyroid cancer. (USPSTF Recommendation level: B, Evidence-fair) (1|)
6) IODINE NUTRITION DURING PREGNANCY
• La Guía 2012 recomienda que la mujer no solo debe
aumentar la ingesta de iodo durante el embarazo y la
lactancia, sino también en el período previo a la concepción: 6.1. Women in the childbearing age should
have an average iodine intake of 150 µg per day. As
long as possible before pregnancy, during pregnancy
and breastfeeding, women should increase their daily
iodine intake to 250 µg on average. (USPSTF Recommendation level: A, Evidence-good) (1|)
• Se reafirma la medición de la ioduria para evaluar la
ingesta de iodo, pero, dado que no es una medición
usual, si no se dispone de la misma, se recomienda
evaluar TSH y niveles de hormonas tiroideas. 6.3.
Although not advised as a part of normal clinical
practice, the adequacy of the iodine intake during
pregnancy in a population, urinary iodine concentration (UIC), should be measured in a representative
cohort of the population. UIC should ideally range
between 150-250 µg/L. If there is a significant concern, the caregiver should assay TSH and thyroid
hormone levels.(USPSTF Recommendation level: A,
Evidence-good) (1|)
• La Guía 2012 incorpora 2 nuevas recomendaciones:
una de ellas se refiere a la necesidad de administrar
en el embarazo vitaminas que contengan iodo y la
otra alude a que, al asegurar una adecuada ingesta de
iodo en la lactante, se asegura también un adecuado
aporte para el bebé: 6.5. We recommend that oncedaily prenatal vitamins contain 150-200 µg iodine
and that this be in the form of potassium iodide or
iodate, the content of which is verified to ensure
that all pregnant women taking prenatal vitamins
are protected from iodine deficiency. Ideally, supplementation should be started before conception.
Preparations containing iron supplementation
should be separated from thyroid hormone administration by at least 4 hours. (USPSTF Recommendation level: B, Evidence-fair) (2|). 6.6
We recommend that breastfeeding women maintain
a daily intake of 250 µg of iodine to ensure breast
milk provides 100 µg iodine per day to the infant.
(USPSTF Recommendation level: A, Evidencegood) (1|)
7) POSTPARTUM THYROIDITIS
• La Guía 2012 aclara que en mujeres eutiroideas con
TPOAb positivos, la primera medición de TSH en el
post-parto debería realizarse a los 6 meses o cuando
esté clínicamente indicado. 7.2. Women known to be
TPO-Ab-positive should have a TSH performed at
6-12 weeks and at 6 months postpartum or as clinically indicated. (USPSTF Recommendation level: A,
Evidence-good) (1| )
• La Guía 2012 agrega, además de la diabetes tipo 1,
otras enfermedades que presentan más a menudo disfunción tiroidea pos-parto y que, por ello, deberían
evaluarse más precozmente y más frecuentemente. 7.3.
Because of the prevalence of PPT in women with type
1 diabetes, Grave’s disease in remission and chronic
viral hepatitis is greater than in the general population,
screening by TSH is recommended at 3 and 6 months
postpartum. (USPSTF Recommendation level: B, Evidence-fair) (1|)
8)SCREENING FOR THYROID DYSFUNCTION
DURING PREGNANCY
Como mencioné al comienzo, es la sección que incorporó mayor número de recomendaciones versus la guía
de 2007.
Respecto al período de preconcepción, la Guía no
autoriza el screening universal, solo identificar a grupos
de alto riesgo. En caso de detectarse mujeres con TSH
mayor de 2.5mUI/L (confirmada con más de un dosaje),
autoriza a que reciban un tratamiento transitorio con
baja dosis de LT4. 8.1a. Universal screening of healthy
women for thyroid dysfunction before pregnancy is
not recommended. (USPSTF Recommendation level:
I, Evidence-poor) (2|). 8.1b. However, caregivers should identify individuals at ‘high risk’ for
thyroid illness (Table 1, see below) on the basis of
their medical history, physical exam or prior biochemical data. When such individuals are identified prenatal measurement of serum TSH is recommended. If it
25
Artículo Comentado
is >2.5 mIU/L, the test should be confirmed by repeat
assay. Although no randomized controlled trials are
available to guide a response, the committee believes it
is appropriate to give low-dose T4 treatment to bring
TSH below 2.5mIU/L. This treatment could be discontinued if the woman does not become pregnant
or postpartum. (USPSTF Recommendation level: I,
Evidence-poor) (2|)
Table 1: Recommended patient profiles for targeted
thyroid disease case finding in women seeking
pregnancy, or newly pregnant
Women > 30 years
Women with a family history or autoimmune thyroid
disease or hypothyroidism
Women with a goiter
Women with thyroid antibodies, primarily thyroid
peroxidase antibodies
Women with symptoms or clinical signs suggestive of
thyroid hypofunction
Women with type 1 diabetes mellitus or other autoimmune
disorders
Women with infertility
Women with a prior history of miscarriage or preterm
delivery
Women with prior therapeutic head or neck irradiation or
prior thyroid surgery
Women currently receiving levothyroxine replacement
Women living in a region with presumed iodine deficiency
• Si toman LT4 previo al embarazo, la Guía recomienda
que todas las mujeres se chequeen con un dosaje de
TSH, buscando niveles menores de 2.5 mUI/l. Si se
embarazan, deben consultarse de forma inmediata
para ser evaluadas o aumentar la dosis a ciegas. (Opinión del autor: esto podría evitarse si se realizaran
ajustes preconcepción buscando TSH menores de 1.2
mUI/L, ya que en esta situación solo un 17%, aproximadamente, de las pacientes, tendría que aumentar
la dosis intraembarazo). 8.2a. All women considering pregnancy with known thyroid dysfunction
and receiving levothyroxine should be tested for
abnormal TSH concentrations before pregnancy.
(1|). 8.2b. All women receiving levothyroxine
who are seeking pregnancy should ideally have their
dosage adjusted to target a preconception TSH of
0.5-2.5 mIU/L. (USPSTF Recommendation level: B,
Evidence-fair) (1|). 8.2c. All women receiving
levothyroxine should be verbally screened prenatally
to assess their understanding of changing levothyroxine requirements following conception. These women
should be counseled to contact a physician or medical
professional immediately upon a missed menstrual
cycle or suspicion of pregnancy to check their serum
26
TSH level. An additional recommendation may be
to increase their levothyroxine dose by 30%, which
is often 2 additional tablets per week (9 tablets/week
instead of 7 tablets/week), until their serum TSH can
be checked. (USPSTF Recommendation level: B, Evidence-fair) (2|)
• La Guía 2012 mantiene que no se acepta el Screening
Universal para la medición de TPOAb previo o luego
de la concepción, aunque si se detecta, recomienda
pesquisar TSH. 8.3a. Universal screening for the presence of anti-TPO antibodies either before or during
pregnancy is not recommended. (USPSTF Recommendation level: C, Evidence level-fair) (2|).
8.3b. However, women with elevated anti-TPO
antibodies are at increased risk for miscarriage, preterm delivery, progression of hypothyroidism and
PPT. Therefore, if identified, such women should be
screened for serum TSH abnormalities before pregnancy as well as during the 1st and 2nd trimesters of
pregnancy. (USPSTF Recommendation level: C, Evidence-fair) (1|) (See also 8.5.).
• No hubo acuerdo en el Comité para el Screening Universal con TSH de todas las mujeres embarazadas en
su primera visita. Se aceptó la evaluación solo en mujeres consideradas de alto riesgo (Ver Tabla 1). Podrá
observarse en dicha tabla que se han agregado 2 categorías más respecto a las que figuraban en la Guía de
2007: mujeres de más de 30 años y aquellas que habitan en áreas con posible iododeficiencia. 8.4a. The
committee could not reach agreement with regard
to screening recommendations for all newly pregnant women. Two versions are therefore presented.
8.4a1. Some members recommended screening
of all pregnant women for serum TSH abnormalities by the 9th week or at the time of their first visit.
(USPSTF Recommendation level: C, Evidence-fair)
(2|) (Authors supporting – LD, JR, JL, NA,
CE). 8.4a2. Some members recommended neither
for nor against universal screening of all pregnant
women for TSH abnormalities at the time of their
first visit. These members strongly support aggressive case finding to identify and test high-risk women
(Table 1) for elevated TSH concentrations by the 9th
week or at the time of their first visit before and during
pregnancy, and recognize in some situations, ascertainment of the individual’s risk status may not be feasible.
In such cases, and where the local practice environment is appropriate, testing of all women by 9 weeks
of pregnancy or at the first prenatal visit is reasonable.
(USPSTF Recommendation level: I, Evidence-poor)
(2|) (Authors supporting – MA, EA, JM, LB,
SS, SM, DL, RC)
• La Guía 2012 reafirma el tratamiento del Hipotiroidismo Subclínico con levotiroxina (y no triyodotiro-
Artículo Comentado
nina) en esta sección, pero no hace diferencias entre
SCH con TPOAb + vs TPOAb, tal como sucedió en la
recom. 1.2.2 de la sección de Hipotiroidismo. En subclinical hypothyroidism and neurological outcome, la
fuerza de la recomendación presenta también una diferencia respecto a la indicada en la recom. 1.2.2: la recomendación debería ser I , en lugar de C. 8.4b. If serum
TSH is >2.5 mIU/L at the time of testing (or >3.0 mIU/L
in the 2nd trimester), levothyroxine therapy should be
instituted. For overt hypothyroidism (USPSTF Recommendation level: A, Evidence-good) (1|); for
subclinical hypothyroidism and obstetrical outcome
(USPSTF Recommendation level: C, Evidence-fair)
(2|); for subclinical hypothyroidism and neurological outcome (USPSTF Recommendation level:
C, evidence poor. (2|OOOO)
• La dosis de levotiroxina recomendada para hipotiroidismo subclínico, descubierto en el embarazo, es “50
mcg o más”. Serán necesarios trabajos futuros que
tiendan a un rápido y mayor control de la disfunción.
8.4c. If TSH concentration is 2.5-10 mIU/L, a starting levothyroxine dose of 50 mcg/day or more is
recommended. Other thyroid preparations (such
as triiodothyronine) are not recommended. (USPSTF Recommendation level: C, Evidence level-fair)
(2|)
• En esta sección se hace nuevamente referencia a los
tiempos en que debe evaluarse a las pacientes con más
riesgo de disfunción post-parto, pero los tiempos sugeridos son diferentes a los de la recom. 7.3 de la sección Post-partum thyroiditis, fundamentalmente en
lo que hace a diabetes tipo 1. 8.5. Women at high-risk
for PPT in the postpartum months should be screened
via assessment of serum TSH. These high-risk groups
include: 1) women known to be TPO Ab+, 2) women
with type 1 diabetes and 3) women with a prior history of PPT. Screening should occur at 6-12 weeks
postpartum. (USPSTF Recommendation level: C, Evidence-poor) (2|) (See also Section 7.)
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27
Commented Article
Accidental occupational exposure to radiation induces
thyroid nodules
Mario A. Pisarev M.D.1

Marta Schnitman M.D.2
Abstract
Lack of appropriate shielding in the X-ray equipments
was detected at the radiology service in a local hospital.
Studies were performed in physicians and technicians
exposed (9 females and 5 males) and in an age and sex
matched group of non-exposed physicians and technicians (8 females and 5 males).
No thyroid abnormalities were found in the non-exposed patients. On the other hand in the exposed cohort,
11 out of 14 had nodular goiter, and 1 presented diffuse
goiter. In 5 out of 12 nodule grew or new nodules appeared. Two patients had increased TSH and 1 increased
TPO antibodies. In another an abnormal TRH-TSH test
was observed, while a 4th patient had low T4 values. In 2
out the 5 male patients sperm abnormalities were detected. Dry-eye syndrome occurred in other 2, while mammary nodules appeared in 1 female and a basocellular
epithelioma in another one. No abnormalities were found
among the controls.
Introduction
The occurrence of nodular goiter after external head and
neck radiation has been reported,1-3 in particular thyroid
nodules and cancer after head and neck irradiation as a treatment for Tenia capitis, and enlarged thymus or tonsils. 4,5
Similar results were reported among survivors from atomic
bomb explosions or nuclear accidents.6,7 An occupational
radiation-induced thyroid nodule in atomic plant workers
was found in China.8 A recent review suggested the generation of autoimmune thyroid disorders under similar circumstances.9 We report the occurrence of thyroid nodules
as a consequence of an accidental occupational radiation
exposure at a local hospital in Buenos Aires. For obvious
reasons the identification of the hospital as well as the identity of the persons involved are not disclosed.
Materials and methods
During a inspection at a radiology service, a lack
of appropriate shielding in the X-rays equipment was
found. The physicians and technicians who operate these
1
Depts. of Radiobiology, National Atomic Energy Commission and of Human Biochemistry, University of Buenos Aires School of Medicine, Buenos Aires, Argentina; 2Service of Endocrinology and Metabolism, Cesar
Milstein Hospital, Buenos Aires, Argentina
28

Guillermo J. Juvenal PhD1
procedures and were exposed to radiation during the
last 24 months were examined. They include 14 persons
(5 males and 9 females), aged between 29 and 54 years.
Studies included a complete clinical work-up, thyroid
ultrasonography, assay of circulating total T3, T4, TSH,
thyroid antibodies, TRH-TSH tests by routine methods,
and fine-needle aspiration (FNA) of thyroid nodules.
Similar studies have been performed in a group of unexposed physicians and technicians: 8 females and 5 males,
aged of 27-60 years.
Estimation of the radiation dose received
by the exposed persons
The technicians operating the equipment perform
around 400 X-ray radiographies per month. Each procedure provides approximately a dose of 1.22 mGy to total
body and 0.94 mGy to the neck, a monthly dose of 488
mGy for total body and 188 mGy for the thyroid. The
accumulated dose for 11 months of work would be 5.36
Gy and 4.12 Gy, respectively.
The physicians take care generally of radioscopies,
especially during surgery, performing 30 shots per day
and 600 per month. It may be estimated that the neck/
thyroid dose is around 732 mGy/month and 6.2 Gy/11
months.
Although all personnel involved wore leaded cloths
they did not protect the neck, making the thyroid the
organ which received the highest doses of radiation.10
Results
As shown in Table 1 most of the radiation-exposed
patients had normal values of circulating T3, T4 and TSH.
However, 2 of them had increased basal TSH with normal
T3 and T4 values, suggesting subclinical hypothyroidism.
One patient had low T4 and another had an abnormal
TRH-TSH test.
The ultrasonographic studies demonstrated that 11 out
of the 14 radiation exposed patients had nodular goiter,
while an additional patient had diffuse goiter. No goiter
or other abnormalities were demonstrated in the nonexposed cohort. Out from the 11 with nodular goiter in
other 5 the follow-up demonstrated nodule growth or the
appearance of new nodules. Other pathologies included
abnormal spermogram in 2 out of 5 male patients, dryeye syndrome in other 2, mammary nodules in 1 female
Commented Article
Table 1 Laboratory values of the exposed cohort
Patient
Gender
Age
T3
T4
TSH
1e
M
43
1.01
104
0.90
2e
F
45
1.32
78
2.46
3e
M
44
1.25
121
1.51
4e
F
47
0.92
65
0.71
5e
F
43
1.55
76
8.00*
6e
F
29
1.65
107
1.45
7e
M
46
1.72
43*
3.12
8e
M
50
1.66
66
5.12
9e
M
42
1.96
80
1.73
10e
F
44
1.17
104
7.75*
11e
F
43
1.57
85
1.72
12e
F
54
1.22
75
4.22
13e
F
44
1.06
79
2.42
14e
F
48
1.19
113
1.00
T3 and T4 values are expressed as nmoles/L and the normal values for our
population are 0.95-2.50 for T3 and 50-137 for T4. TSH values are expressed
as mU/mL, and the normal range is 0.5-5.0*, p < 0.01 when compared to the
corresponding controls.
and a basocellular epithelioma in another one (Table 2).
The cytological examination of the FNA samples from the
patients with nodular goiter did not provide evidence of
malignant transformation. The non-exposed cohort did
not show any abnormality either in thyroid anatomy or
function (Table 3).
From the data obtained it may be concluded:
a) In 11 out of 14 radiation-exposed patients nodular goiter
was developed and an additional patient had diffuse goiter. Therefore total goiter incidence was 12/14 (85.7%).
b)In 5 of the nodular goiter patients an increase in the size
or the appearance of new nodules was observed along
the follow-up period. No cancer was detected by FNA.
c) Hypothyroidism was observed in 3/14 patients, and
an additional patient had an abnormal TRH-TSH test,
suggesting subclinical hypothyroidism.
d)Increased circulating antithyroid antibodies were
found in 1 of the hypothyroid patients.
e) Significant changes in the spermogram were documented in 2 out of the 5 exposed males. Previous to the
accidental exposure to radiation they were fertile and
had normal children.
f) Dry-eye syndrome was observed in 2/14 patients.
Table 2 Changes in thyroid morphology and in other organs
Patient
Thyroid Sonography
Other organs
Comments
1e
08/08/01:2 nodules in RL 4x3 mm and 3x2 mm
06/02/03: 4 nodules in RL 5x3 mm, 4x3 mm,
3x2 mm and 3x3 mm
Spermogram in 2001 showed important
impairment in morphology and
motility of spermatozoids
2e
Heterogeneous, in LL a nodule of 6.4 mm
diameter
Right mammary nodules
3e
No significant changes
Very important alterations in
spermogram
Previously the patient
gave birth to 2 children
4e
09/24/02: RL: 2 nodules of 5x2 mm and 5x3
mm; LL: 1 nodule of 23x13 mm
06/02/03: RL: 2 nodules of 8x4 mm and 5x3
mm; LL: no change
Basocellular epitheliomas in face
(surgically excised)
Abnormal TRH-TSH test
5e
11/28/00: RL multiple micronodules and
a dominant of 12x7 mm; LL multiple
micronodules
05/08/03: no change
6e
09/20/01: RL nodule 4x3 mm; LL: nodule 5x4
mm
05/08/03: RL nodule 6.1 mm diameter and
another of 5 mm diameter; LL nodule 9.2 mm
diameter
7e
07/03/01:RL nodule 4.3 mm diameter
05/08/03: RL nodule 6 mm diameter
8e
Heterogeneous
9e
06/03/03: LL 2 nodules of 6x3 mm and 4x2 mm
10e
Diffuse enlargement, heterogeneous
FNA: thyroiditis
ATPOAb: 94.6 IU/mL
ATgAb: 458.8 IU/mL
29
Commented Article
Table 2 Changes in thyroid morphology and in other organs
Patient
Thyroid Sonography
Other organs
Comments
11e
10/02/01: LL: heterogeneous, nodule of 5x4
mm
05/08/03: no change
12e
10/01/01:RL: 3 nodules 9.9 mm, 5.2 mm and
3.7 mm diameter; LL: 3 nodules 9.6 mm, 10.8
mm and 4.3 mm diameter
05/08/03: no change
Dry-eye syndrome
FNA : benign
13e
11/10/99: RL: nodule of 3.5x3 mm
14e
12/21/00: RL nodule 9x6 mm
Dry-eye syndrome
10/04/01:RL no change; LL: nodule 6x5 mm
Diffuse epithelial queratitis
09/26/02: RL nodule 11x7x8 mm; LL: no
change
05/08/03: RL: 2 nodules 12.4x10.8x6.3 mm and
6x5x4 mm; LL 2 nodules 4.5x4 mm and 4.7x2.6
mm
RL: right thyroid lobe, LL: left thyroid lobe, ATPO: anti-thyroid peroxidase antibodies, ATg: anti-thyroglobulin antibodies.
Table 3 Studies performed in the unexposed group
Patnt.
Gender
Age
Sonog.
T4
FreeT4
T3
TSH
ATPO
ATg
1c
F
32
Negat.
8.0
1.3
120
1.0
< 20
< 20
2c
F
26
Negat.
7.0
1.4
90
2.9
< 20
< 20
3c
F
46
Negat.
7.2
1.5
120
3.8
< 20
< 20
4c
F
40
Negat.
8.5
1.1
75
1.1
< 20
< 20
5c
F
43
Negat.
7.9
1.2
130
2.6
< 20
< 20
6c
F
60
Negat.
5.4
1.0
97
2.0
< 20
< 20
7c
M
42
Negat.
6.6
120
2.1
< 20
< 20
8c
M
48
Negat.
9.1
1.3
160
1.3
< 20
< 20
9c
F
42
Negat.
6.1
1.1
120
3.9
< 20
< 20
10c
F
48
Negat.
8.3
1.3
130
0.78
< 20
< 20
11c
M
48
Negat.
6.8
1.2
130
1.7
< 20
< 20
12c
M
27
Negat.
4.5
1.2
100
3.4
< 20
< 20
13c
M
54
Negat.
5.8
1.1
130
1.2
< 20
< 20
T3 and T4 values are expressed as nmoles/L and the normal values for our population are 0.95-2.50 for T3 and 50-137 for T4. TSH values are expressed as mU/
mL, and the normal range is 0.5-5.0. ATPO: anti-peroxidase antibodies; ATg: anti-thyroglobulin antibodies.
Discussion
The incidence of nodular goiter among the general population was investigated in studies performed in
the USA and in the United Kingdom. The results of the
Framingham (USA) study showed that 6.4% of women
and 1.6% of males presented thyroid nodules.11 A similar study, performed in the northwest of Great Britain,
showed an incidence of 8.6%.12 Therefore we may conclude that the incidence of nodular goiter found in the
present study largely exceeds that which might be expec-
30
ted in the general non-irradiated population. Besides
in the control group, composed of physicians and technicians, matched by age and sex, no thyroid nodules or
abnormalities were found. Both groups live in the area of
Buenos Aires city where iodized salt has been consumed
since 1967. The causal relationship between radiation and
thyroid abnormalities is also supported by the finding of
hypothyroidism and increased levels of thyroid autoantibodies. The changes in the spermogram of some males
and the occurrence of the dry-eye syndrome may also be
related to the irradiation.
Commented Article
Although it has been reported that young people have
higher sensitivity to radiation-induced thyroid disease,
the present data, which includes patients with an age
range of 29-54 years, indicates that adults are also susceptible. There might be a great variability between the time
of irradiation and the appearance of thyroid abnormalities, as already suggested by others,13 and therefore careful follow-up should be made of the irradiated patients in
order to detect any new abnormalities.
The dose received at the neck by our patients was estimated to be between 4.12 and 6.2 Gy/year. This is a non
lethal dose and fits with previous studies which established that doses as low as 10 cGy can cause the appearance
of thyroid disease.3,13 DeGroot reported that an external
radiation dose of 2-3 Gy (200-500 rads) increases the incidence of thyroid nodules by 2% per year.14 Other study
concluded that the dose required to induce the appearance of thyroid nodules and cancer may have a variation between 100 rads and 6,000 rads.15 The incidence
of nodular goiter was found to be significantly increased
among the workers at a nuclear power plant in Germany.
In this study the dose received was estimated to be around
70-400 mSv.16 Therefore we may conclude that the present
results confirm the causal relationship between the accidental occupational irradiation of the neck and the increased incidence of thyroid nodules.
Acknowledgements: Part of this study was supported
by grants from the Argentine National Research Council
(CONICET), the National Agency for the Promotion of
Science and Technology (ANPCYT), the University of
Buenos Aires, the National Atomic Energy Commission
(CNEA) and Montpeller Laboratories S.A. MAP and GJJ
are Established Investigators of the CONICET.
References
1. DeGroot LJ. Radiation and thyroid disease. Baillieres Clin. Endocrinol. Metab.
1998; 2: 777-91.
2. Van Middlesworth L. Effects of radiation on the thyroid gland. Adv. Internal
Medicine. 1989; 89: 265-84.
3. Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, Schneider AB,
Tucker MA, Boice Jr JD. Thyroid cancer after exposure to external radiation: a pooled
analysis of seven studies. Radiation Res. 1995; 141: 259-77.
4. Schneider AB, Bekerman C, Favus M, Frohman LA, Gonzalez C, Ryo UY, Sieversten G, Pinsky S. Continuing occurrence of thyroid nodules after head and neck
irradiation. Ann. Int. Med. 1981; 94: 176-80.
5. Pretorius HT, Katikineni M, Kinsella TJ, Barsky SH, Brennan MF, Chu EW, Robbins
J. Thyroid nodules after high-dose external radiotherapy. JAMA. 1982; 247:3217-20.
6. Yoshimoto Y, Ezaki H, Etoh R, Hiraoka T, Akiba S. Prevalence rate of thyroid
diseases among autopsy cases of the atomic bomb survivors in Hiroshima, 1951-1985.
Radiation Res. 1995; 141:278-86.
7. Inskip PD, Hartshorne MF, Tekkel M, Rahu M, Veidebaum T, Auvinen A, Crooks
LA, Littlefield G, McFee AF, Salomaa S, Mäkinen S, Tucker JD, Sorensen KJ, Bigbee WL,
Boice Jr JD. Thyroid nodularity and cancer among Chernobyl cleanup workers from
Estonia. Radiation Res. 1997; 147:225-35.
8. Wang JX, Zhang A, Li BX, Zhao YC, Wang ZQ, Zhang JY, Aoyama T. Cancer
incidence and risk estimation among medical X-ray workers in China, 1950-1995. Health Phys. 2002; 82: 455-66.
9. Eheman CR, Garbe P, Tuttle RM. Autoimmune thyroid disease associated with
environmental thyroidal irradiation. Thyroid. 2003; 13: 453-64.
10. Prasad KM. Handbook of Radiobiology, 2nd ed. New York: CRC Press; 1984.
11. Vander JB, Gaston EA, Dawber TR. The significance of non-toxic thyroid nodules: final report of a 15 year study of the incidence of thyroid malignancy. Ann. Int.
Med. 1968; 69: 537-40.
12. Tunbridge WMG, Evered DC, Hall R 1995. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Wickham survey. Clin. Endocr.
(Oxford). 1995; 43: 55-69.
13. Schneider AB; Ron E; Lubin J; Stovall M; Gierlowski TC. Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the
prolonged effects of radiation on the thyroid. J.clin. Endocr. Metab. 1993; 77: 362-9.
14. DeGroot LJ. Diagnostic approach and management of patients exposed to irradiation to the thyroid. J. Clin. Endocrinol. Metab. 1989; 69: 925-8.
15. Asteris GT; DeGroot LJ. Thyroid cancer: relationship to radiation exposure and
to pregnancy. J. Reproductive Medicine. 1976; 17: 209-15.
16. Kindler S; Roser M; Below, Hoffmann, Kohlmann; Kramer A; Kirsch G; Volzke H.
Thyroid disorders in employees of a nuclear power plant. Thyroid. 2006; 16: 1009-17.
31
XV Latin American Thyroid
Congress – Abstract
Abstracts: Poster
POSTER
Thyroid Cancer Clinical
PO001 CORRELAÇÃO ENTRE CÂNCER DE TIREOIDE
E TIREOIDITE DE HASHIMOTO
Gama RR1; Talini C1; Kaminski JH1 1
Hospital Universitário Evangélico de Curitiba (HUEC) Introdução: A associação entre tireoidite de Hashimoto
(TH) e o carcinoma de tireoide (CT), descrita pela primeira
vez em 1955, é largamente debatida no meio científico, pois
essas doenças compartilham diversos aspectos morfológicos, imuno-histoquímicos e biomoleculares. Metodologia:
Foram analisados 125 prontuários de pacientes submetidos
à tireoidectomia por doenças benignas e malignas da tireoide
no período de 8 anos. Resultados: Os pacientes foram separados em 2 grupos: grupo A – com câncer de tireoide (74
casos) – e B – sem câncer (52 casos). Neste estudo, 36,59%
dos pacientes que apresentaram câncer de tireoide possuíam
também tireoidite de Hashimoto diagnosticada laboratorialmente ou no exame anatomopatológico, enquanto que 20,55%
dos pacientes sem câncer de tireoide apresentaram tireoidite
de Hashimoto, valores estes que demonstraram associação
estatisticamente significante entre TH e CT (p=0,03352). As
patologias de tireoide, tanto benignas quanto malignas, foram
mais frequentes no sexo feminino (86,4%). Dentre os critérios
de agressividade nos pacientes com câncer de tireoide não
houve diferença estatística significante entre pacientes portadores de tireoidite de Hashimoto e não portadores, com os
respectivos valores de p: 0,12 para invasão capsular; 0,38 para
invasão extratireoidiana; 0,08 para metástase linfonodal; 0,95
para tamanho tumoral e 0,60 para multifocalidade. Apenas
foi encontrada diferença estatística significativa no critério
invasão vascular (p=0,01), a qual foi mais frequente nos casos
sem Hashimoto. Conclusão: Este estudo demonstrou que
existe correlação significativa entre a tireoidite de Hashimoto
e o câncer de tireoide, porém o câncer não se mostrou mais
agressivo nos pacientes portadores dessa doença autoimune.
Palavras-chave: tireoidite de Hashimoto; carcinoma papilífero; câncer de tireoide.
PO002 ABLATION IN LOW RISK PAPILLARY THYROID
CANCER. YES OR NO COMPARISON OF 3 METHODS
Degrossi E1; Degrossi O1; Baubuena R2
Departament Image, Sanat, Otamendi; 2Hospital Alemán 1
Background: Surgery plus ablation (A) is the primary treatment of thyroid cancer. A is controversy with the low risk
papillary form (LR-PTC). Objectives: a) to confirm if TRHTSH stimulation (TRH-ST) is adequate for A;1 b) to considerer if A is adequate in LR-PTC. Material and method: A was
carried out in 114 pts considered LR-PTC using 3 methods
to increase TSH.2 G-I in 33 pts TRH-ST was used starting in
day 8 after surgery and A in day 13. G-II in 54 pts deleting
hormonal treatment for 4-5 weeks was indicated; G-III in 27
pts rhTSH was utilized. Pts were followed-up during 1.5 to 5.5
years, mean 3.5 y, and were considered free of disease (FoD) or
with relapse or metastases (RoM). Results: G-I TSH 109±106
mU/L (35-360), FoD 96,6%, RoM 3,4%; G-II TSH 92±76
mU/L (31-229), FoD 96%, RoM 4%; G-III TSH 138±32 mU/L
(82-318), FoD 95.9%, RoM 4,1%. No statistical differences
were found in follow-up. In TSH values G-II p<0.05 with reference to G-I and G-II and G-I p<0.05 to G-II. Discussion: No
differences were found among the 3 method employed, indicating that TRH-ST use is adequate to obtain A. The 4% of
cases with RoM were, of course, erroneously included on LR
group. Similar observation was reported previously.2 In cases
without A, RoM is more than 15% at 5 years and increased
as time goes by.3 People are living more. For these reasons we
considered that A must be used in LT-PTC. References
1. Degrossi et al. Rev Argent Endocr Metab. 2010; 44 (2): 3-13.
2. Tuttle et al. Thyrodi. 2010; 20:1341-9.
3 Mazzaferri & Jhiang. Am Clin Climatol Assoc J. 1995; 106: 151-70.
Keywords: ablation; low risk papillary; thyroid cancer.
PO003 RESPONSE TO SORAFENIB IN METASTATIC
ADVANCED THYROID CARCINOMA
Pitoia F1
Private Office 1
Objective: Investigate the efficacy of sorafenib in progressive
radioiodine-resistant metastatic thyroid carcinoma. Design: Off-label observational study. Sorafenib 400 mg twice
daily was evaluated. The primary endpoint was the objective
RECIST score assessed on day 30 and every 12 weeks thereafter. Additional endpoints were duration of tumor response and
changes in tumor marker (thyroglobulin) measured, initially,
at 4 weeks and then every 4 weeks. Therapy duration was 9±5
months. Results: Eight patients were included (7 papillary, 1
insular variant). The 8 patients meeting study criteria received
sorafenib 400 mg orally twice a day until disease progression
or unacceptable toxicity development. One patient showed a
partial response with tumor regression of 35% 6 months after
the beginning of treatment; 5 patients exhibited stable disease
and 2 patients were not evaluable (only 3 months of treatment). Thyroglobulin decreased within 2 weeks in all patients
with follicular derived thyroid cancer by 50%±23%. Adverse
events: One patient died because of sudden death (congestive
heart failure). This patient had suffered a previous miocardiopathy related to sorafenib which originated the withdrawal of
the drug 9 months after starting. Other adverse events were:
fatigue (n=3), diarrhea (n=3), hand-foot syndrome (n=1),
rash (n=1) and hair loss (n=1). Hypertension was not observed. In 2 patients sorafenib dose was reduced to 400 mg/d
and in other 2 to 600 mg/d. Four patients are on full dosage
(800 mg/d), 1 after 9 months of treatment. Conclusion: These
data suggest a possible role for sorafenib in the treatment of
progressive metastatic DTC.
Keywords: metastatic; advanced; sorafenib.
PO004 OUTCOME OF PATIENTS WITH DIFFERENTIATED
THYROID CANCER ACCORDING TO ATA AND LATS RISK
OF RECURRENCE CLASSIFICATIONS
Pitoia F1; Abelleira E1; Bueno F1; Urciuoli C1; Salvai ME1; Cross G1;
Niepomniszcze H + (in memoriam) 1
1
Hospital de Clinicas/University of Buenos Aires Objectives: To evaluate rates of persistent disease (PD) in
patients with DTC according to American Thyroid Association
(ATA) and Latin-American Thyroid Society (LATS) risk of
recurrence (RR) classifications, to compare between this 2 categorizations. Subjects and methods: Definitions: Biochemical
persistence (BP): (Tg > 1 ng/mL, under treatment or after stimulation) with no evidence of structural disease. Structural
recurrence (SR) clinically identifiable disease. Tg-Ab positive
patients were excluded. We reviewed 355 records of DTC
33
Abstracts: Poster
patients, and 171 were included (all papillary DTC, mean
age 45±16 y, followed-up for 64±48 months after initial treatment, TNM Stages E I n=99, E II n=12, E III n=29 y E IV=31
(IV A=21; IV B=3; IV C =7). Results: PD was observed in
79/171 (46%) subjects. PD (BP/SR) according to ATA and
LATS RR classifications were: 1) ATA: Low: 20% (50%-50%);
Intermediate 59% (62%-38%); High 65% (90%-10%)(p<
0,01 Low versus Intermediate; p<0,001 Low versus High;
p=NS Intermediate versus High), 2) LATS: Very Low: 13%
(60%-40%); Low: 16% (40%-60%); High: 57% (30%-70%).
Very Low versus Low p=NS; Low/Very Low versus High, p<
0,001). There were no differences when ATA intermediate or
high RR was compared with LATS High RR. Conclusions:
Our data supports that PD is closely related to the RR from
both guidelines. It is probable that Very low and Low risk
LATS could be joined and that Intermediate ATA needed a
better characterization to discriminate more accurately those
patients with moderate RR that wasn’t so for our patients.
Keywords: risk; recurrence; cancer.
PO005 INDOLENT OUTCOME OF PATIENTS WITH
DIFFERENTIATED THYROID CANCER AND BIOCHEMICAL
PERSISTENCE OF DISEASE
Pitoia F1; Abelleira E1; Bueno F1; Urciuoli C1; Niepomniszcze H
(in memoriam)1
1
Hospital de Clinicas/University of Buenos Aires Objetive: Evaluate the outcome of patients with DTC
and biochemical persistence (BP) after initial treatment
(total thyroidectomy with or without lymph node dissection (LND) and thyroid remnant ablation). Subjects and
methods: Biochemical Persistence (BP): (Tg>1 ng/mL,
under treatment or after stimulation) with no evidence of
structural disease. Structural Recurrence (SR): clinically
identifiable disease. Tg-Ab positive patients were excluded.
We reviewed 355 records of DTC patients and 28 were included (mean age 42±12 years, TNM Stages EI, n=21 (75%),
EIII n=6 (21%), EIVA n=1 (4%); risk of recurrence LATS
was: Very low: n=3, Low: n=5 and High: n=20. All subjects
had Tg levels <1 ng/mL under therapy. TSH stimulation was
performed after withdrawal or rhTSH (same way in each
subject). Patients were divided into 3 groups: G-1: Tg 1-2
ng/mL; G-2: Tg 2-10 ng/mL; G-3: Tg >10 ng/mL. Results: In
5/28 (18%) patients SR was observed after a mean follow-up
of 70±32 months. In G-1: 2 (7%) patients remained with BP
after a mean follow-up of 24±17 months. In G-2: 17 (61%)
patients remained with BP after 31±21 months and 4/17
(24%) subjects had lymph node SR. After LND, all of them
remained with BP 20±9 months after re-treatment. In G-3: 9
(32%) patients had BP after 40±30 months of follow-up; 1/9
(11%) had a SR. LND was performed but BP was observed
60 months after the new surgery. Conclusion: Most patients
with DTC and BP present an indolent course of the disease.
Keywords: biochemical persistence; thyroid cancer; risk of
recurrence.
PO006 ANÁLISE DO ESVAZIAMENTO DO COMPARTIMENTO
CENTRAL PROFILÁTICO EM PACIENTES SUBMETIDOS À
TIREOIDECTOMIA TOTAL POR CARCINOMA PAPILÍFERO
DE TIREOIDE
Montoro JRMC1; Miranda FA1; Degrande MP1; Pretti VP1; Arruda GV1;
Affonso VR1; Uvo SAB1
1
Faculdade de Medicina de Marília (FAMEMA) 34
Introdução: O câncer da tireoide é o mais comum da região da
cabeça e do pescoço, e, destes, o carcinoma papilífero é o mais
prevalente. O tratamento é essencialmente cirúrgico, sendo
recomendada a tireoidectomia total. Em relação ao pescoço,
nos casos de linfonodo positivo, é indicado o esvaziamento
cervical, mas nos casos N0 o esvaziamento ainda é controverso.
Objetivo: Analisar as complicações em pacientes submetidos
à tireoidectomia total e esvaziamento cervical do nível VI por
carcinoma papilífero de tireoide N0 e compará-las com pacientes que foram submetidos somente à tireoidectomia total.
Método: Foi realizada análise retrospectiva de pacientes operados no período de janeiro de 2001 a setembro de 2011. Os
pacientes foram divididos em 2 grupos, um grupo que foi submetido a tireoidectomia total com esvaziamento do nível VI, e
o outro que foi submetido somente à tireoidectomia total. Os
grupos foram comparados em relação à presença de disfonia,
hipoparatireoidismo e recidiva, pelo teste exato de Fischer. Foi
realizada análise univariada entre os grupos para recidiva em
relação ao sexo, idade, tamanho do tumor e presença de linfonodo metastático. Foi considerado p< 0,05 como significativo.
Resultados: Dos 88 pacientes, 80,7% eram do sexo feminino,
e 77,3% foram submetidos ao esvaziamento do nível VI. Com
base na classificação de risco, 42% eram de muito baixo risco,
18,2% de baixo risco, e 39,8% de alto risco. Apresentaram disfonia 9 pacientes, sendo destes 66,7% com esvaziamento e 33,3%
sem esvaziamento (p=0,333). O hipoparatireoidismo ocorreu em 19 pacientes, dos quais 84,2% fizeram esvaziamento,
e 15,8% não (p=0,316). A recidiva ocorreu em 10 pacientes,
dos quais 70% fizeram esvaziamento, e 30% não (p=0,406).
Pela análise variada, não houve significância estatística entre os
grupos para recidiva. Conclusão: O esvaziamento cervical do
nível VI é um procedimento seguro que não aumenta as complicações, porém sua realização não diminui a recidiva.
Palavras-chave: carcinoma papilar; tireoidectomia; glândula
tireoide.
PO007 METÁSTASE CÍSTICA CERVICAL COMO PRIMEIRA
MANIFESTAÇÃO DO CARCINOMA PAPILÍFERO DE TIREOIDE
Oliveira-Filho JRF1; Rodrigues MM1; Santos VJB1; Nadai TR1
1
Hospital Estadual de Américo Brasiliense (HEAB)
Introdução: A metástase cística cervical como primeira manifestação de um carcinoma papilífero de tireoide é uma condição
extremamente incomum, podendo confundir-se com as outras
formações císticas cervicais adquiridas ou de origem congênita. Objetivo: Apresentar o caso de uma paciente portadora
de uma massa cística cervical volumosa em íntima relação com
a veia jugular interna direita, causando um abaulamento com
deformidade estética do pescoço. Apesar de fazer diagnóstico
diferencial com cisto branquial, tratava-se de uma metástase
de carcinoma papilífero de tireoide. Métodos: Paciente do
sexo feminino, com idade de 40 anos, apresentava uma massa
cervical volumosa, móvel, depressível e indolor na face lateral
do pescoço. A natureza cística da lesão foi demonstrada por
uma tomografia computadorizada. A tireoide apresentava
um aspecto multinodular e não era palpável ao exame físico.
Resultados: O diagnóstico foi feito por punção aspirativa por
agulha fina. Com o resultado da citologia, a paciente foi submetida a uma tireoidectomia total com esvaziamento cervical
radical modificado ipsilateral ao cisto, seguido por terapia com
radioiodo. A paciente segue em acompanhamento no ambulatório do HEAB sem sinais de recidiva. Conclusões: Em um
Abstracts: Poster
paciente com cisto cervical lateral, o diagnóstico diferencial com
metástase cística de carcinoma papilífero de tireoide deve ser
considerado. Qualquer massa cervical lateral, sendo sólida ou
cística, requer uma punção aspirativa por agulha fina, podendo
ser guiada por ultrassonografia para definição citológica. Na
confirmação do diagnóstico, o tratamento com tireoidectomia
total e esvaziamento cervical radical modificado preservando
apenas o nível I do pescoço, seguido de radioiodoterapia, oferece a terapêutica adequada.
Palavras-chave: metástase cística; tireoide; carcinoma papilífero.
PO008 TECIDO TIREOIDIANO ECTÓPICO EM LINHA MÉDIA
ASSOCIADO À TIREOIDITE DE HASHIMOTO
Hospital Universitário Américo Brasiliense (HEAB) 1
Introdução: O tecido tireoidiano ectópico ocorre geralmente
devido a uma falha de migração da tireoide durante a vida
fetal. Ela pode estar presente em qualquer lugar entre a base
da língua e o sítio normal da tireoide no nível do 2o ao 4o anel
traqueal, geralmente aparecendo como lesões da linha média.
Objetivo: Apresentar o caso de uma paciente portadora de um
nódulo cervical em linha média do pescoço, em íntima relação com o osso hioide, estando logo abaixo deste e anteriormente a laringe, mimetizando um cisto do duto tireoglosso
ou metástase de carcinoma folicular de tireoide. Métodos:
Sexo feminino, 61 anos, apresentando tumoração cervical em
linha mediana, indolor à palpação e com consistência sólida.
Submetida a uma tomografia cervical que diagnosticou uma
tireoide tópica, heterogênea, com formação nodular calcificada de 6 mm em lobo esquerdo, com lobo direito reduzido e uma formação nodular de 3,0 cm x 1,9 cm, imediatamente abaixo do osso hioide. Resultados: O diagnóstico foi
feito através de punção aspirativa por agulha fina (PAAF) e a
paciente submetida à tireoidectomia total associada à ressecção do nódulo ectópico. A patologia acusou uma tireoidite
de Hashimoto associada a uma glândula tireoide acessória. O
diagnóstico diferencial com metástase de carcinoma folicular
deveu-se à ausência de invasão vascular e capsular de toda a
série histológica. Conclusões: O tecido tireoidiano ectópico
localizado em linha média está relacionado a uma desordem
no desenvolvimento tireoidiano no período embrionário, faz
diagnóstico diferencial com cistos congênitos e é difícil sua
diferenciação da metástase de carcinoma folicular. O tratamento cirúrgico é simples e resolutivo.
Palavras-chave: tireoide; ectópica; tireoidite de Hashimoto.
PO009 CARCINOMA TIROIDEO LOCALMENTE INVASIVO
EN TRÁQUEA. TRATAMIENTO ONCOLÓGICO Y POSTERIOR
TRAQUEOPLASTÍA ALEJADA POR DEHISCENCIA DE
ANASTOMOSIS TRAQUEAL
Zund S1; Patané K2; Califano I1; Lupo E1; Rufino C1; Saco P1 1
Instituto AH Roffo; 2Instituto María Ferrer Introducción: El objetivo del tratamiento del carcinoma papilar de tiroides (CPT) con invasión traqueal es resecar satisfactoriamente la enfermedad conservando las funciones. La resección circunferencial traqueal y anastomosis se recomienda ante
compromiso del espesor de la pared. La estenosis traqueal es
una complicación del procedimiento. Presentamos un caso
de CPT con compromiso traqueal, cuyo tratamiento quirúrgico oncológico evolucionó con una complicación severa, y
su manejo. Caso clínico: Paciente mujer de 27 años, con masa
tiroidea que fue explorada en otro centro y declarada irresecable. Compromiso traqueal evidenciado por tomografía.
Lesión endoluminal confirmada por fibrolaringoscopia. Se
efectuó tiroidectomía total, linfadenectomía recurrencial bilateral (conservando ambos nervios laríngeos inferiores), linfadenectomía selectiva II-V bilateral + resección y anastomosis
traqueal (7 anillos). AP: CPT T4a N1b M0 EI. Presentó fístula
traqueal, posterior dehiscencia total de la anastomosis y finalmente requirió de una traqueostomía. Evolución con estenosis traqueal del cabo proximal. Recibió 200 mCi 131I (rastreo
post-dosis positivo lecho); Tg preablación 2,6 ng/mL y AcTg
negativos. Controles: ecografía negativa, Tg bajo inhibición
0,2 ng/mL y TAC cuello y tórax negativa. A los 16 meses, se
efectuó traqueoplastía con resección de 3 anillos traqueales
más y anastomosis cricotraqueal, con evolución favorable, sin
fístula traqueal, con movimiento cordal normal y sin disfonía. Discusión: La resección traqueal segmentaria es de elección cuando hay compromiso local sin enfermedad a distancia. La estenosis es una complicación del procedimiento, cuya
resolución debe plantearse una vez que el tumor primario está
controlado. La traqueoplastía permite obtener un resultado
funcional satisfactorio en estos casos.
Palabras clave: cáncer de tiroides; cirugía; invasión traqueal.
PO010 METÁSTASES SINCRÔNICAS PARA TIREOIDE
E PULMÃO DE ADENOCARCINOMA NO INTESTINO
Silva SJ1; Mamede JF1; Moraes1; Silva MVF1; Silva VTTM1; Cordeiro
MS1; Ferreira KS1
1
Universidade Federal de Uberlândia (UFU) Metástases para tireoide são incomuns, apesar de o órgão ser
ricamente vascularizado; as manifestações clínicas são raras,
e sua prevalência varia de 1% a 43%, dependendo do estádio do tumor primário. Relatamos o caso de uma mulher, 74
anos, faioderma, que evoluiu com metástase sincrônica para
tireoide e pulmão após 6 anos do diagnóstico de adenocarcinoma colorretal. Em consulta-rotina, foi evidenciada imagem
hiperdensa em base de pulmão direito em raios-x de tórax.
Após confirmada lesão em tomografia computadorizada de
tórax, foi submetida à mediastinoscopia para estadiamento da
lesão. Durante o procedimento, foi visualizado nódulo em lobo
esquerdo tireoidiano, tendo sido este biopsiado em mesmo
tempo cirúrgico. Ao exame histopatológico, mostrou tratar-se
de adenocarcinoma metastático. Após orientar a paciente,
optou-se pela tireoidectomia total e lobectomia de lobo pulmonar inferior direito. A análise do espécime cirúrgico confirmou, em ambos os sítios, adenocarcinoma metastático. Em
seguimento, foi submetida à quimio e radioterapia adjuvantes,
encontrando-se até o momento assintomática. A evolução do
caso foi compatível com o achado cirúrgico e ausência de manifestações clínicas, uma vez que o prognóstico torna-se sombrio
em caso de sintomatologia dessas metástases.
Palavras-chave: metástases; tireoide; pulmão.
Hyperthyroidism
PO011 ENFERMEDAD DE GRAVES: VENTAJAS DEL
TRATAMIENTO COMBINADO METIMAZOL + T3 EN
RELACIÓN A METIMAZOL SOLO
Vázquez A1; Calabrese C1; Alcaraz G1; Abalovich M1; Calletti F1;
Simoni Y1; Tkatch J1; Frydman M1; Levalle O1; Gutiérrez S1 1
División de Endocrinología, HOSPITAL DURAND 35
Abstracts: Poster
Introducción: Existen controversias sobre el tratamiento
metimazol + hormona tiroidea en Enfermedad de Graves.
Objetivo: Evaluar retrospectivamente si metimazol + triyodotironina tiene ventajas sobre metimazol solo. Métodos: Se
evaluaron 132 pacientes con Enfermedad de Graves (> 1año
de tratamiento y de seguimiento post-suspensión): 109 mujeres y 23 varones [Edad (x ± DS): 39,1 ± 12,6 años]: 79 con
metimazol + T3 [TC] y 53 metimazol solo [MS]. Se midieron
TSH, T4, T3, TRAb, captaciones de I131 y tamaño tiroideo
por palpación. Resultados: No hubo diferencias significativas
entre ambos grupos en relación a edad, mujer/varón, tiempo
de evolución pretratamiento, tabaquismo, presencia de oftalmopatía, tamaño del bocio, captación I131, T3/T4, niveles
de TRAb, T4 o T3 séricos. La dosis inicial de metimazol fue
significativamente diferente (TC: 52,6 ± 12,4; MS: 38,2 ±
18,4 mg/d; p<0,0001), no así la dosis final. La prevalencia de
hipotiroidismo intratratamiento y su severidad no difirieron,
pero sí la duración del mismo (TC: 1,7 ± 2,5; MS: 2,9 ± 3,1
m; p<0,003) y el número de veces que requirió modificarse la
dosis de metimazol por año (TC: 3,6 ± 1,4; MS: 5 ± 2 veces/a;
p< 0,0004). La remisión a largo plazo no difirió con ambos
tratamientos (TC 39,2 %; MS 35.8%), si bien hubo una tendencia al retraso de la recurrencia en el TC. La negativización
del TRAb al final del TC permitió predecir dicha remisión.
Conclusiones: Ventajas del tratamiento combinado: menor
número de visitas con eventual reducción de costos, menor
duración de hipotiroidismo intratratamiento con probable
beneficio en oftalmopatía, mayor intervalo libre de enfermedad y predicción de remisión en pacientes con TRAb negativos. Esto avala su vigencia.
Palabras clave: enfermedad de Graves; tratamiento de bloqueo reemplazo; metimazol + triyodotironina.
PO012 HIPERTIROIDISMO, VASCULITIS ASOCIADA A
PROPILTIOURACILO
Jiménez M1; Gottchaslk C1; Iturrieta V2; Granzotto C1; Sepúlveda G1;
Roa JC1; Schnerberger P1
1
Clínica Alemana Temuco; 2Universidad de La Frontera Varón de 63 años. Antecedentes: tabaquismo (1 cigarrillo
diario), >40 años, cáncer de colon operado y quimioterapia,
libre de enfermedad. Presenta cuadro de 8 meses de evolución caracterizado por intolerancia al calor, temblor fino,
palpitaciones que limitan su actividad física, nerviosismo,
sudoración, insomnio, diarrea intermitente, asociado a baja
de peso de 9 kg. Durante el último mes se diagnostica hipertensión arterial. Exámenes de laboratorio destacan: TSH <
0,004 uUI/mL, T3: >600 ng/dL y T4L >6 ng/dL. Evaluación
oftalmológica: exoftalmometría Herthel (104 mm) 14 y 13
mm derecho e izquierdo, respectivamente, y CAS 0 puntos.
Inició tratamiento con propiltiouracilo 300 mg y propanolol
120 mg por día, con buena tolerancia digestiva. A las 48 horas
de los medicamentos evoluciona con lesiones petequiales,
confluentes y pruriginosas, en región distal de extremidades
inferiores, agregándose ulceraciones dolorosas, sin fiebre,
ni compromiso de mucosas. Estudio inmunológico mostró
ANCA p: 1,4 U (negativo), TRAB 73% y exámenes inmunológicos restantes negativos. Hemograma, pruebas hepáticas
y sedimento de orina, normales. Se diagnosticó vasculitis
secundaria a propiltiouracilo, suspendiéndose este último.
Evaluación a cargo de un equipo médico: endocrinólogo,
cirujano, oftalmólogo de órbita, radiólogo, cardiólogo. Se
36
indica tiroidectomía casi total y se inicia la preparación
rápida con amiodarona 200 mg y propranolol 40mg cada
6 h; betametasona 2 mg im cada 12 h por 5 días. Con esto,
disminuyen los síntomas de hipertiroidismo, la hemodinamia queda estable y las lesiones de la piel desaparecen paulatinamente. Se realiza tiroidectomía sin incidentes. Buena
evolución post-operatoria. La biopsia concluye: tiroides con
cambios inflamatorios compatibles con la Enfermedad de
Basedow Graves.
Palabras clave: enfermadad basedow Graves; propiltiuracilo;
tratamiento.
PO013 COLESTIRAMINA: ALTERNATIVA TERAPÉUTICA EN
EL TRATAMIENTO DEL HIPERTIROIDISMO
Munizaga F1; Munizaga C1
1
Hospital Clínico San Borja-Arriarán, Unidad de Endocrinología. Universidad
de Chile. Campus Central Introducción: En el hipertiroidismo, la circulación enterohepática de las hormonas tiroideas está aumentada y la
Colestiramina (C) es una resina de intercambio iónico que
secuestra T4 en el intestino, aumentando su excreción fecal. Por
eso, es interesante analizarla como alternativa terapéutica en el
tratamiento del hipertiroidismo. Objetivos: Evaluar respuesta
terapéutica acortada de pacientes tratados con Colestiramina
en hipertiroidismo. Material y Métodos: Estudio de casoscontrol (CS-CT) en pacientes con hipertiroidismo clínico y/o
de laboratorio, a quienes se les administra Colestiramina 16gr/
día por 7 días, en conjunto con drogas antitiroideas (Metimazol
30 mg) y Propanolol (entre 40-160mg/día). El grupo control recibe antitiroideos y propanolol. Se controla tolerancia y adherencia de la terapia y control de
T4 y T3 al 7o día. Valores normales: T4: 4,5-11,2 ug/dL, T3: 0,97-1,69 ng/mL. Resultados: n Edad Sexo Etiología CS 12 34,0 5H/ 7M EBG14 /BMN1 CT 7 30,1 3H/ 4M EBG7 T4 (día 0) T4 (día 7) T3 (día 0) T3 (día 7) CS 28,66+8,57 14,13+5,39(a) 5,20+2,11 2,25+1,05(b) CT 26,15+7,88 25,33+7,27 4,02+1,44 3,69 +1,29 (a) p<0,01, (b) p<0,03 Buena tolerancia oral y adherencia. Conclusiones: El uso de Colestiramina por 7 días disminuye
significativamente los niveles de T4 y T3. Por lo tanto, es una
alternativa útil para el manejo del paciente hipertiroideo.
Palabras clave: hipertiroidismo; tratamiento acortado; colestiramina.
PO014 TOTAL THYROIDECTOMY FOR GRAVES DISEASE: A
GOOD OPTION FOR SELECTED CASES
Volpi EM1; Steck JH2; Vasconcelos ECG3; Mahmoud RRGL1;
Aizawa RK1; Cernea CR1; Araujo Filho VJF1
1
University of São Paulo; 2Hospital Mario Gatti;3University Federal de Curitiba Background: The preferred mode for therapy in Graves
Disease (GD) is antithyroid drugs or radioactive iodine
being surgery an exception reserved for a small number of
patients. Objectives: To evaluate the results of total thyroidectomy for treatment of patients that for some reason
were not eligible for treatment with radioactive iodine and/
or the treatment with antithyroid drugs was discontinued
or failed. Abstracts: Poster
Methods: From January 2005 to July 2012, 19 patients with
GD were undergone to total thyroidectomy. All of them
were females with age ranging from 17 to 44 years. The
volume of the gland ranged from 16-65 gr. The reasons
that led to surgery were lack of effective response to clinical treatment due to intolerance to medication or severe
side effects, allergy, intolerance to iodine and refusal of the
patient to radioactive iodine therapy or preference to surgery. Results: The length of hospital stay ranged from 1-12
days with 4 patients requiring hospitalization for up to a
week prior to surgery for preoperative care. Two patients
had transient unilateral vocal fold palsy with no cases
with permanent lesion of vocal fold, 6 showed transient
hypoparathyroidism recovering up to 2 months and 2 had
permanent hypoparathyroidism. All the patients had a fast
regression of the symptoms including in 2 cases ophthalmopathy. Ninety-five per cent of patients were satisfied
with surgery. Conclusions: Surgery is not the first option,
but in selected cases is a good tool, with low levels of complication and a fast patient recover.
Keywords: hyperthyroidism; thyroidectomy; graves disease.
PO015 OFTALMOPATIA DE GRAVES: QUADRO GRAVE COM
ALTERAÇÕES HORMONAIS LEVES: RELATO DE CASO
Pontes AAN1; Pequeno TA1; Meneguesso AMA1; Matos LL1;
Sena CM1; Rêgo ACC1; Capote Júnior JRFG1
1
Hospital Universitário Alcides Carneiro/Universidade Federal de Campina
Grande (HUAC/UFCG) Introdução: A oftalmopatia associada ao hipertireoidismo
é uma doença autoimune, cujo quadro clínico é variável,
dependendo do grau da infiltração dos tecidos. O aumento
da pressão intraorbital leva ao prejuízo na drenagem venosa
episcleral, com consequente glaucoma e dor ocular. Relato
de caso: M.G.A, 57 anos, do lar, divorciada, portadora de
hipertensão, procurou o ambulatório de endocrinologia do
HUAC/UFCG, em caráter de urgência, por se encontrar
com bastante dor ocular, protrusão, diplopia, edema e hiperemia importantes nos 2 olhos. Tal quadro havia iniciado há
6 meses, com piora há 2. Relatava, também, discretas palpitações, perda peso, insônia, tremores e sudorese esporádica. Ao exame, apresentava-se com exoftalmia importante,
edema palpebral e conjuntival, quemose bilateral, fotofobia,
PA = 200 x 110 mmHg, FC = 100 bpm e escore 6 pelo escore
de atividade clínica. Foram solicitados TSH, T4 lvire, ATPO,
TRAB, hemograma, TGO, TGP, TC de órbitas e parecer do
oftalmologista. Iniciou-se Propranolol 40 mg, VO, 12/12h;
Prednisona 20 mg/dia (depois 40 mg); Albendazol 400 mg/5
dias; lubrificante ocular; Ciprofloxacino 500 mg, VO, 12/12h
(lesão MIE) e Enalapril 10 mg, VO, 12/12h. Resultados dos
exames: TSH=0,01 mUI/mL; T4 livre = 2,24 ng/dL (VR=0,81,9 ng/dL); Anti-TPO=0,1 UI/mL e TRAB=8,13 UI/mL,
prescreveu-se Tapazol®, 20 mg/dia. Em 5 dias, o quadro
ocular regrediu 30%. Discussão e Conclusão: A oftalmopatia de Graves apresenta evolução independente, e mesmo o
estado de hipertireoidismo leve ou eutireóideo não implica
regressão ou estabilização do quadro ocular. Logo, a multiplicidade de manifestações clínicas e a gravidade dessa
doença demonstram que cada caso deve ser avaliado separadamente.
Palavras-chave: oftalmopatia de Graves; hipertireoidismo;
tireoide.
PO016 SPINDLE EPITHELIAL TUMOR WITH THYMUS-LIKE
DIFFERENTIATION (SETTLE) IN A 12-YEARS-OLD MALE
Da Silva PCA1; Nascimento PR1; Lee JS1; Nascimento ML1;
Cechinel E1; Linhares RMM1; Simoni G1; Aust J2; Vieira D2
1
Hospital Infantil Joana de Gusmao; 2Universidade Federal de Santa Catarina
(UFSC) Background: Spindle Epithelial Tumor with Thymus-like
Differentiation is rare with 42 cases reported in English
language literature until 2010. It is a malignant neoplasm
which occurs predominantly in children, adolescents and
young adults. It was first described as a cervical tumor derived from ectopic thymic tissue or remnants of the branquial
pouch. SETTLE seems to behave as a low-grade malignancy,
with potential of sending late metastases. Therewith patients
should receive special attention in the initial diagnosis and
long term follow up after resection of the lesion. Patient
report: A 12-year-old boy was referred to us with cervical
nodule and right cervical lymphadenopathy. Laboratory testing revealed normal thyroid function. Neck ultrasound showed a hypoechoic nodule with irregular borders and gross
calcifications within, measuring 2.2x1.4x1.8 cm in the right
lobe of the thyroid and bilateral cervical lymph nodes. The
patient subsequently underwent fine needle aspiration biopsy
of the thyroid nodule, with pathologic criteria for medullary
thyroid carcinoma, spindle cell variant. Total thyroidectomy
and resection of cervical lymph nodes were performed, which
confirmed, by histological findings and immunohistochemistry study, the diagnosis of SETTLE. Conclusion: A longterm follow-up is recommended since these patients may
develop late metastases. With early diagnosis and prompt
surgical intervention, this patient would be expected to have
a favorable prognosis, since the benefits of radiotherapy and
chemotherapy are not yet clear because of the rare nature of
the tumor.
Keywords: settle tumor; cancer; thymus like.
PO017 SELECTIVE INDICATION OF PROPHYLACTIC
CENTRAL NECK DISSECTION IN PAPILLARY THYROID
CANCER
De Carvalho AY1; Chulam TC1; Fernandes WB1; Kowalski LP1
Hospital A. C. Camargo 1
Background: The indication of prophylactic central
neck dissection in papillary thyroid cancer is controversial. Objectives: The aim of this retrospective cohort study
was to assess long term results of observation versus. prophylactic central neck dissection in patients with papillary
thyroid carcinoma preoperatively and intraoperatively staged as N0, submitted thyroidectomy. Patients and methods:
From 1996 to 2007 a total of 812 patients were submitted
to thyroidectomy due to thyroid cancer in a tertiary cancer center. A group of 580 consecutive patients with previously untreated papillary thyroid cancer without lymph
node metastasis detected by clinical examination and ultrasound (cN0) and also with negative macroscopic findings
during the surgical procedure were eligible for the study. Of
the 580 patients, 102 (Group A) underwent thyroidectomy
with elective central neck dissection, while 478 (Group B)
underwent thyroidectomy alone. The indication of nodal
dissection was at surgeon’s discretion. Demographic, clinical and pathological features were analysed. Statistical
37
Abstracts: Poster
analysis included chi-square test and significance was set
at p<0.05. Results: In Group A patients the rates of occult
metastatic disease was 67.2% (all pN1a). Group A patients
were younger, their tumors were larger in size (mean of 14.8
mm versus 10.2 mm, p<0.0001) and had vascular lymphatic
invasion more frequently. More patients in Group A were
treated with adjuvant radioiodine and received larger doses.
The rates of postoperative infection and hematoma requiring reoperation were not significantly different between the
2 groups. Group A patients had higher rates of temporary
hypocalcemia (47.1% versus 32.2%; p=0.004) and permanent hypoparathyroidism (12.1% versus 2.65%; p<0.001).
The incidence of temporary and permanent recurrent
laryngeal nerve dysfunction was also significantly higher in
Group A patients: 10.7% versus 6.0% (p=0.042), and 5.9%
versus 1.4% (p=0.015), respectively. With a mean follow-up
of 80.2 (Group A) versus 67.4 (Group B) months, overall
recurrence rate was 1.9% (11/580), with 3.9% (4/102) in
Group A, and 1.5% (7/580) in Group B. In Group A patients
all recurrences occurred in lymph nodes outside the level
VI. Conclusion: Although the risk of occult lymph node
metastases reaches 67% in a selected group of patients, the
elective indication of central compartment dissection for
patients with papillary thyroid carcinoma increases the risk
of complications and do not contribute to the loco-regional
control rates.
Keywords: papillary thyroid cancer; prophylactic central
neck dissection; selective indication.
PO018 STATISTICAL CASES OF DIFFERENTIATED THYROID
CARCINOMA IN A GOVERNMENT HOSPITAL OF SÃO PAULO
Bueno TL1; Guerra RA1; Portes ES1; Santos LM1; Ramalho MCB1;
Vale AMC1
1
Departamento de Endocrinologia e Metabologia/Instituto de Assistencia
Médica ao Servidor Público Estadual (IAMSPE) Introduction: The increased incidence of thyroid cancer is
a worldwide trend partly explained by the indiscriminate
increase of applications for ultrasound and cervical incidentalomas. Objective: The aim of this study was to perform a
statistical case of differentiated thyroid carcinoma (DTC) of
our service. Methods: This was an observational study performed at the clinic of thyroid cancer of IAMSPE/SP during
the period November 2011 to October 2012. Patients were
assessed through an elective and the data were evaluated: date
of surgery, histological type, histological variant, tumor size
and tumor staging. Results: During 12 months we evaluated the data of 202 patients with DTC. We found 181 cases
of papillary (89.6%), and 21 follicular (10.4%). The average
age of patients at diagnosis was 52.5 years, and micropapillary accounted for 48% of all cases. Considering only the
papillary, we find that the average tumor size was 1.39 cm,
and 56.4% of the classical variant, 31.2% of follicular, 6.1%
of hurthle cell, 2.7% of sclerosing, 1.1% of trabecular, 1.1% of
clear cell, and 1.1% of tall cell. Conclusion: We found that our
sample is similar to the literature, with a higher prevalence
of papillary tumors and especially in women. This points the
average tumor size follicular carcinoma as well as staging of
the largest tumor diagnosis. This feature was also observed in
men who had the highest tumors compared to women.
Keywords: differentiated thyroid carcinoma; statistical cases;
observational study.
38
PO019 INCIDÊNCIA DO CÂNCER DE TIREOIDE
EM PACIENTES TIREOIDECTOMIZADOS NA CIDADE
DE ARAGUAÍNA – TOCANTINS
Coelho T1; Feltrim EN1; Medrado R1
Instituto Harmonia
1
Introdução: O câncer de tireoide é a neoplasia endócrina
mais frequente, a prevalência de nódulos tireoidianos na
população é bastante elevada, sendo malignos em cerca de
5% do total. Objetivo: Fazer uma análise epidemiológica e
a incidência de câncer da tireoide em pacientes tireoidectomizados em nossa região. Métodos: Revisão de 61 prontuários de pacientes submetidos à tireoidectomia entre janeiro
de 2011 e fevereiro de 2012, sendo analisadas informações
quanto ao sexo, tamanho dos nódulos, resultados de ultrassonografia, punção aspirativa por agulha fina (PAAF) e anatomopatológico. Resultados: Observou-se uma prevalência
de pacientes do sexo feminino. Nestes pacientes, o tamanho
do nódulo foi <1,5 cm em 18%, 43% entre 1,5 cm e 3 cm,
29% >3,1 cm, e 10% apresentaram nódulos bilaterais. Foi realizada a PAAF de 46 pacientes e classificados em suspeitos,
malignos, benigno. Os pacientes foram submetidos à tireoidectomia e os resultados mostraram quando PAAF benignos,
8% tinham câncer; PAAF maligno comprovou em 100%; em
pacientes com PAAF suspeito, 30% foram confirmados com
câncer no anátomo partológio. Conclusão: O câncer foi identificado em 18% de todos os pacientes operados; a incidência
de câncer em nódulos suspeitos é bastante elevada. Referências: Cooper DS, Doherty GM, Haugen BR et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov; 19(11):1167-214.
Goldman, L; Ausiello, D. Cecil medicina. 23. ed. Rio de Janeiro: Elsevier;
2009. Rosa, JC da; Romão, LA. Glândula Tireóide – funções e disfunções, diagnóstico
e tratamento. 2. ed. São Paulo: Lemos Editorial;2002.
Palavras-chave: tireoide; câncer; bócio.
PO020 COMPLICATIONS IN THYROIDECTOMY:
NOW AND THEN
Lira RB1; Fiho JG1; Kowalski LP1
Department of Head and Neck Surgery and Otorhinolaryngology/Hospital
AC Camargo 1
Background: Thyroidectomy is one of the most common surgical procedures performed in the world, and several modifications in its technique have been described in recent decades. Objectives: To evaluate the profile of complications in
thyroid surgery nowadays and compare this with last decade‘s
experience of the same group. Methods: We reviewed 1321
consecutive patients submitted to thyroid surgery from 2008
to 2010. Total thyroidectomy was performed in 1067 patients
(80.8%). Central compartment neck dissection was done
in 162 patients (12.3%) and lateral dissection in 33 patients
(2.5%). This data was compared with previous published data
by the same department. Results: Postoperative complications occurred in 272 patients (20.6%). Hypocalcemia was the
most frequent complication (transient 8%; permanent 2.6%),
followed by vocal fold paresis (transient 6.4%; permanent 2%).
The incidence of postoperative complications was influenced
by the extent of thyroidectomy (22% in total thyroidectomies
against 37.5% in the extended thyroidectomies) the association
of paratracheal (33.8%), and lateral neck dissection (78.8%).
In the 1990’s, there was a higher incidence of hypocalcemia
(transient 38%; permanent 6.8%), and a lower incidence of
Abstracts: Poster
vocal cord paresis (transient 3.1%; permanent 0.3%). These
changes can be explained, respectively, by a rising search for
parathyroid preservation techniques and better evaluation of
vocal cord mobility. Conclusion: This study demonstrates that
the extent of thyroidectomy and the association of neck dissection have a major role on the incidence of complications.
Furthermore, technical developments and more intensive evaluation in thyroidectomy can lead to better understanding and
prevention of complications.
Keywords: thyroidectomy; complications; neck dissection.
Thyroid cancer basic
PO021 RELAÇÃO DOS NÍVEIS DO HORMÔNIO
ESTIMULANTE DA TIREOIDE (TSH) COM A MALIGNIDADE
EM NÓDULOS DE TIREOIDE
Colombo BS1; Conceição TMB2; Canalli JS2; Colombo G1;
Pasinato APBF1; Schneider IJC2; Canalli MHBS1
1
Hospital Universitário Polydoro Ernani de São Thiago/Universidade Federal
de Santa Catarina (HU/UFSC);2Universidade do Sul de Santa Catarina
(UNISUL) Introdução: Associação entre níveis elevados de TSH
como fator trófico à célula tireoidiana e maior prevalência de câncer tireoidiano tem sido discutida. Objetivos:
Relacionar os níveis de TSH em valores de corte, conforme a literatura, com a malignidade em nódulos de
tireoide (NT). Material e métodos: Estudo transversal
de 159 prontuários (171 NTs) no HU/UFSC de agosto de
2010/2012. Realizadas avaliações cito-histopatológicas e
do TSH em ensaio de quimioluminescência (3a geração)
à época da punção aspirativa e categorizado em pontos de
corte. Pacientes com disfunção tireoidiana estabelecida ou
em tratamento foram excluídos. Análises estatísticas com
teste do x2 ou Fisher e significância em p<0,05. Resultados:
A média de idade dos pacientes foi 48 anos, com 92,4%
mulheres; 2,9%, 64,3%, 5,3%, 10,5%, 8,8% e 8,2% dos NTs
com Bethesda I a VI, respectivamente. O TSH variou de
0,08 a 10,5 (média: 1,965±1,69; mediana: 1,48) uUI/mL.
Trinta e cinco NTs foram operados, sendo 74,3% malignos
e, desses, 80,8% carcinomas papilíferos. Análises em grupamentos de Bethesda e cito-histopatológicas (casos operados + não operados com citopatologias II, V e VI = 150
NTs) em valores de corte de TSH <1, ≥1, <1,8 e ≥1,8 uUI/
mL evidenciaram significância apenas em 1,8, com 32,7%
dos NTs Bethesda II e 71,4% dos Bethesda VI ≥1,8, confirmando-se à cito-histopatologia, em que 33,9% de 115
NTs benignos vs 60% de 35 malignos apresentavam TSH
≥1,8 uUI/mL (p = 0,006). Conclusão: Malignidade em NT
relacionou-se com valor de corte de TSH ≥ 1,8 uUI/mL.
Palavras-chave: nódulo de tireoide; câncer de tireoide; hormônio estimulante da tireoide (TSH).
Thyroid nodule
PO022 COMPARAÇÃO ENTRE TERMOGRAFIA E DOPPLER
DE NÓDULOS TIREOIDIANOS BIOPSIADOS
Alves MLD1; Duarte GG2; Gabarra MHC1
1
Universidade de Ribeirão Preto (UNAERP);2 Fundação Faculdade de
Medicina da Universidade de São Paulo (FM/USP) A tireoide, devido à sua localização superficial, é facilmente
acessível à exploração ultrassonográfica, termográfica e
biópsia aspirativa. A punção aspirativa com agulha fina
(PAAF) é considerada o método diagnóstico pré-operatório mais sensível na identificação de nódulo tireoidiano
maligno. O uso de ultrassonografia na avaliação da região
cervical levou à detecção de grande número de nódulos
impalpáveis e controvérsias sobre a necessidade de serem
todos eles analisados para malignidade. O exame ultrassonográfico com Doppler colorido avaliando as características
de vascularização dos nódulos tireoidianos e sua associação
com malignidade é uma alternativa possível. A tireoide já
foi alvo de estudos de teletermografia, que consegue determinar faixas de diferenças térmica que sugeririam malignidade nas lesões examinadas. Com o intuito de comparar
esses 2 métodos de avaliação da vascularização de nódulos
tireoidianos e sua possível correlação com malignidade,
avaliamos 332 mulheres e 26 homens portadores de nódulos tireoidianos detectados à palpação e confirmados com
exame de Doppler colorido seguido de punção biópsia aspirativa do maior número de nódulos detectados e análise
citopatológica do esfregaço obtido e comparamos com os
achados de 92 mulheres e 18 homens avaliados pela teletermografia. Os achados de sensibilidade foram de 15,78% e
100%; especificidade de 98,52% e 95%; valor preditivo positivo de 37,50% e 78,00%; valor preditivo negativo de 95,42%
e 100% e acurácia de 94,13% e 88%, respectivamente para
Doppler e teletermografia. Esses nossos dados sugerem que
a teletermografia foi mais precisa na avaliação da vascularização de nódulos tireoidianos sugestivos de malignidade e
na indicação de biópsia.
Palavras-chave: termografia; Doppler; nódulo tireoidiano.
PO023 THYROID NODULES AND RISK FACTORS
ASSOCIATED WITH MALIGNANCY
Coelho SFM1; Bezerra FSM1; Ferraz TMBL1; Mota RMS1;
Macedo LML1; Mota JIS1
1
Hospital Geral de Fortaleza (HGF) Background: Thyroid Nodule (TN) is one of the most common endocrinopathies (4). It is important to identify the criteria of malignancy, increased risk for malignancy, solid TN,
incomplete halo, hypoechoic node, microcalcifications, irregular margins and increased nodular flow (3). Fine-needle aspiration biopsy is presented as a method of defining malignancy in
management and monitoring (2). The present study is justified
in to seek association of TN with malignancy for early diagnosis of cancer. Objectives: Assess TN regarding their clinical,
laboratory, ultrasound, cytology, histopathology and risk factors associated with malignancy, associating TSH, atypical and
malignant lymph nodes. Methods: This is a retrospective study,
descriptive and cross-sectional by chart review. Developed in
a tertiary public hospital, the Hospital Geral de Fortaleza. The
sample is 27 patients with TN that underwent total or partial
thyroidectomy. The analysis used Fisher’s exact test, MannWhitney and relative risk (RR) for associations whose p≤0.05.
Results: The mean age of patients with malignant NT was
44.4±11.7. Presence of microcalcifications and solid nodule
(U.S) was strongly associated with malignancy (57.1% versus
42.9%, p=0.015) and (78.6% versus 21.4%, p=0.02), respectively. Incomplete halo (44.4% versus 56.6%, p=0.024), and atypical lymph (U.S) (74.1% versus 25.9% p=0.005). There was no
association between age, TSH level, nodule size, and malignancy. Of all Bethesda (5 and 6), 6 (22.2%) were malignant.
Conclusion: The RR for malignancy was: solid nodule (2.9,
39
Abstracts: Poster
CI=1.05-8.18); incomplete Halo (5.60, CI=1.00-36.61); microcalcifications (2.6 CI=1.52-4.52); atypical lymph (2.8, CI=1.575.19), showing significance for these factors. References
pacientes con acromegalia. Correlacionar el volumen tiroideo
(VT) y el tamaño de NT con el tiempo de evolución de la
enfermedad (TE), GH e IGF1. Pacientes y método: Desde
2003 a la fecha, se les realizó una ecografía tiroidea a 103
American Thyroid Association. Revised American thyroid association manapacientes con acromegalia: 29 hombres y 74 mujeres. GH e
gement guidelines for patients with thyroid nodules and differentiated thyroid
IGF fueron realizadas por quimioluminiscencia. Resultados:
cancer. Thyroid. 2009; 19(11): 1167-1214.
El 49,5%(51/103) presentó NT. Hubo 38 NT mayor de 10
Keywords: thyroid nodule; risk factors; malignancy.
mm. Se realizaron 32 punciones: no diagnóstica 3,1%(1),
PO024 ¿PUEDE LA ECOGRAFÍA CON POWER DOPPLER
benigna 84%(27), sugerente de lesión folicular 9,3%(3) y CT
AYUDAR EN LA PREDICCIÓN DE MALIGNIDAD DE LOS
papilar 3,1%(1). 6 pacientes no se puncionaron por aspecto
NÓDULOS TIROIDEOS?
coloideo. De los 3 pacientes con sospecha de lesión folicuMunizaga F1 lar, 1 resultó con hiperplasia nodular coloidea y los otros 2
1
Hospital Clínico San Borja-Arriarán. Universidad de Chile aún no han sido tiroidectomizados. TE, niveles altos de GH
Introducción: Las características que sugieren malignidad en e IGF1 se correlacionaron con mayor VT(p=0,023, p=0,033
el estudio de nódulos están definidas. El uso del Doppler es y p=0,0381, respectivamente; no así con mayor tamaño de
controversial. Material y métodos: Estudio hecho sobre 380 NT. Conclusiones: Hubo correlación positiva entre TE, GH e
pacientes que presentaron nódulo tiroideo único o prominente IGF1 con mayor VT. En la mitad de los pacientes hubo lesión
(400 nódulos). Se realiza examen clínico y ecografía que caracnodular en tiroides, siendo un 9,3% sugerente de lesión foliterizan nódulos con componentes sólidos (tipo, ecogenicidad,
cular. A pesar de ser similar a la población general, estos datos
bordes, presencia de calcificaciones, más alto que ancho). El
permiten señalar la necesidad de que se realicen estudios
doppler power se clasifica en 4 tipos: 1. Flujo ausente o escaso. 2. Flujo periférico. 3. Flujo central y periférico (mixto). 4. ecográficos en pacientes con acromegalia. No encontramos
Flujo central, caótico o de arterias perforantes. Punción bióp- mayor frecuencia de CT.
sica que se clasificó como maligna, folicular, benigna e inde- Palabras clave: nódulo tiroideo, bocio; acromegalia.
terminada. Niveles de TSH. Resultados: Punción: Maligna
47, Neoplasia folicular 22, Benigna 268, Indeterminada 63. Se Thyroid Cancer Clinical
estudiaron 400 nódulos en 380 pacientes. De estos, 109 fueron
PO026 ANALYSIS OF PRE-THYROGLOBULIN DOSE OF
operados: 69 por punción maligna o folicular; 10 indetermi- RADIOACTIVE IODINE IN PATIENTS WITH DIFFERENTIATED
nados y 30 de patología benigna por nódulos sintomáticos o THYROID CARCINOMA
porque crecieron durante su evolución. Cáncer: 50 papilares y
Bueno TL1; Guerra RA1; Portes ES1; Ferro KM1; Marocco TS1
7 foliculares. Para la comparación ecográfica se consideraron
1
Departamento de Endocrinologia e Metabologia/Instituto de Assistencia
los pacientes con punción positiva y hallazgo de cáncer en
Medica ao Servidor Público Estadual (IAMSPE) pieza anatomía patológica. Ultrasonografía: fue significativa
Introduction: Papillary thyroid carcinoma (PTC) is the
la presencia de bordes irregulares, hipoecogenicidad y presencia de microcalcificaciones para cáncer (p<0,01). No hubo most common thyroid neoplasms.The measurement of
thyroglobulin (Tg) immediately before the radioactive
correlación con niveles de TSH. iodine (Tg pre-dose), with TSH > 30 mIU/L, shows a direct
Doppler correlation with metastasis and represents a good prognos(tipo de flujo) n 1
2
3
4 † tic marker. Objective: The aim of this study was to try to
Cáncer 57 5
6
9
37*
correlate levels of Tg pre-dose with evidence of recurrence
Benigna 343 107* 198* 32 6 or tumor recurrence by stimulated Tg (Tg-e) > 2.0 ng/mL
and cervical ultrasound (U.S.) post surgery. Methods: We
*p<0,01, †
SENSIBILIDAD: 64,9%, ESPECIFICIDAD: 98,3%, VPP: 86, VPN: 94,4, OR: selected 73 patients with CPT, anti-Tg negative and who
underwent tt followed by administration of radioactive
6,49 iodine. The values of Tg pre-dose were correlated with the
Conclusiones: la ecografía Doppler, el flujo tipo 4, es un ele- current status of the patient, taking into account the cervical
mento más predictor significativo de malignidad en estudio U.S., Tg-values and the presence or not of locoregional or
del nódulo tiroideo.
distant metastasis. Results: Patients were divided according
Palabras clave: nódulo; ecografía; doppler.
to the values of the Tg pre-dose in 4 groups: A, B, C and D,
with group A (Tg ≤ 1.0 ng/mL, n=23, 31.5%), group B (Tg
PO025 ESTUDIO ECOGRÁFICO DE TIROIDES EN
between 1 and 2 ng/mL, n=8, 10.9%), group C (Tg between
PACIENTES CON ACROMEGALIA
2 and 10 ng/mL, n=25, 34.2%) and group D (Tg >10 ng/
Millar ES1; Véliz J1; Díaz RE1; Rojas D2; García M3; Brantes S1; Wohllk N1 mL, n=17, 23.2%). Conclusion: As observed in the litera1
Sección Endocrinología, Hospital del Salvador, Universidad de Chile;
2
ture, the dosage and Tg-associated with cervical U.S. are the
Instituto de Neurocirugía Asenjo, Universidad de Chile; 3Sección
Endocrinología, Hospital del Salvador
best tools for the following CPT. In our service, the lowest
Introducción: La acromegalia se caracteriza por la excesiva values of Tg pre-dosing were associated with less evidence
producción de GH e IGF1 y se asocia a una mayor prevalen- of locoregional or distant metastasis through the methods
cia de neoplasias benignas y malignas. Se describe una mayor mentioned above.
incidencia de bocio, nódulos tiroideos (NT) y cáncer de tiroi- Keywords: papillary thyroid carcinoma; stimulated thyroglodes (CT). Objetivo: Determinar la morfología de bocio en 103 bulin; following post operative.
40
Abstracts: Poster
Thyroid Nodule
PO028 EVALUATION OF PERCUTANEOUS ETHANOL
INJECTION AS THYROID NODULES TREATMENT
Piaia C1; Cadore AC1; Ferreira MC2
1
Universidade Comunitária da Região de Chapecó; 2Universidade
Comunitária da Região de Chapecó e Hospital das Clínicas da Faculdade de
Medicina da Universidade de São Paulo (HC/FMUSP)
Introduction: It has been showed that the percutaneous ethanol injection (PEI) has good results as thyroid nodules therapy. This treatment causes complex and irreversible local tissue lesion without affecting extranodular tissue, nevertheless
it is not a largely used procedure and its effectiveness is still
discussed. Objective: Evaluate PEI effectiveness in the long
term treatment of cystic and mixed benign thyroid nodules. Methodology: Thirty-six nodules were submitted to PEI
guided by ultrassonography (age 40.4±12.9 years). The control
group consisted of 13 individuals in which that therapy was not
used (47±9.5 years). The participants were followed by 8 to 45
months after PEI (IC95% 11-17.3) and the control group by
8-68 months (IC95% 15.1-36.9). Results: In the treated group,
the initial volume of 10.4±9.8 cm³ was immediately reduced
after PEI to 2.9±3.1 cm³ (p<0.001), obtaining a reduction of
67.7%± 19.9%. In the follow up, the nodular volume was 2±2.5
cm³ (p<0.001) versus the initial volume with a reduction
of 78.2%±19.8%, showing that it was bigger after follow-up
(p=0.009). The control group presented an initial volume
of 5.8±3.4 cm³, and after follow-up 6.2±3 cm³ (p=0.507).
Comparing this result with the treated ones the nodular
volume reduction was significantly bigger in the treated with
PEI (p<0.001). Conclusion: The nodular volume reduction is
effective comparing the treated with PEI and the non-treated,
with sustained results in the long term treatment.
Keywords: thydoid; nodules; percutaneous ethanol injection.
PO029 NON-SURGICAL MANAGEMENT OF BENIGN
THYROID CYSTS: EVALUATION OF 79 CASES OF
ULTRASOUND GUIDED ETHANOL SCLEROTHERAPY
Marchi MFS1; Bonamigo LF1; Couto CH2; Barros RC3
1
Fundação Universidade Regional de Blumenau (FURB); 2 Department of
Endocrinology/Hospital Santa Isabel; 3Ecomax Centro de Diagnóstico por
Imagem Background: Thyroid nodules are common in clinical practice. Ultrasound guided ethanol sclerotherapy,
an alternative to other surgical and clinical methods, is a
safe and effective procedure for the treatment of benign
cysts. Objectives: Determine the efficacy and safety of
ultrasound guided ethanol sclerotherapy for benign thyroid
cysts. Methods: Retrospective study, in which 79 patients
with cystic nodules, confirmed by fine-needle aspiration
biopsy, were selected for evaluation after they have undergone at least 2 sessions of ultrasound guided ethanol sclerotherapy. All sessions were performed at the Centro de
Imagens Ecomax, Blumenau, Santa Catarina, Brazil, from
2004 to 2012. Results: Seventy-nine patients were selected
for this study, 70 (88.61%) women. Single nodules were
present in 73 patients (92.41%), and multiple nodules were
identified in 6 (7.59%). The patients were divided into 2
groups. In the first group, the patients underwent up to 3
sessions (29 patients), and in the second, from 4 to 7 sessions (50 patients). The mean reduction in the first group
was 71.33%, in the second group, the mean reduction was
82.79%, with no significant difference (p=0.0671). The general mean reduction was 78.58%. Conclusions: Literature
suggests that ultrasound guided ethanol sclerotherapy is
an effective option for the management of benign thyroid
cysts, with treatment response that varies from 49%-90%. In
this study, the values found were similar to those previously
reported. This research emphasizes that ultrasound guided
ethanol sclerotherapy is a secure and the effective method
for the proper treatment of benign thyroid cysts.
Keywords: ethanol ablation; thyroid cyst; thyroid nodule.
PO030 OCCURRENCE OF SARCOIDOSIS IN A PATIENT
THAT HAS PREVIOUSLY UNDERWENT PERCUTANEOUS
ETHANOL ABLATION OF A SOLID THYROID NODULE
Marchi MFS1; Kuhn M1; Couto CH2
1
Fundacao Universidade Regional de Blumenau (FURB); 3Department of
Endocrinology, Hospital Santa Isabel/Blumenau/Brazil Background: Sarcoidosis is a multisytemic and inflammatory condition of unknown etiology that may affect almost
all organs, most frequently the lungs and intrathoracic lymph
nodes. This disease is manifested by the presence of non-caseating granulomas in affected organ tissues, leading to clinical
sequelae. Objectives: Report the development of sarcoidosis
in a patient that underwent percutaneous ethanol ablation
for a cystic thyroid nodule and thyroidectomy. Methods: We
describe the clinical course of this patient along with the clinical, laboratory, imaging and pathologic findings. Results: A
32-year-old woman, noticed an increase in a nodule located on
the right lobe of the thyroid and lymphadenopathy of the right
cervical nodes with no other clinical manifestations. Ten years
ago she underwent 8 sessions of percutaneous ethanol ablation
in a solid nodule with a total reduction of 81%. Two years ago
the patient noticed an enlargement of the thyroid nodule, US
findings showed a thin hypoechoic halo, with central and peripheral vascularity and hypoechoic lymph nodes. After 2 years
she underwent a total thyroidectomy and lymphadenectomy,
which disclosed a colloid nodular goiter and chronic granulomatous lymphadenitis in 13 lymph nodes, consistent with
sarcoidosis. CT scans of the abdomen and thorax revealed
multiple nodules in the spleen and nodules along with areas
of ground-glass attenuation in both lungs. Conclusions: As
sarcoidosis was developed afterwards the ethanol ablation, we
wonder whether the procedure was the triggering factor or if
this condition was due to previous thyroid disease. The goal of
this report is to question this possibility.
Keywords: sarcoidosis; ethanol ablation; thyroidectomy.
Hyperthyroidism
PO031 TRATAMIENTO CON CORTICOIDES ENDOVENOSO
EN OFTALMOPATÍA DE GRAVES
Zunino A1; Delfino L1; Ilera V1; Sapia V1; Silva Croome MC1; Gauna A1 1
Hospital Ramos Mejía Introducción: La oftalmopatía de Graves (OG) se presenta
en forma severa en un 3%-5% de los casos, y requiere un
tratamiento inmunosupresor, siendo los corticoides sistémicos el Gold Standard terapéutico. Diferentes protocolos
incluyen la administración vía intraocular, oral/endovenosa
o combinada. Objetivos: Evaluar la respuesta al tratamiento
con corticoides endovenosos en OG moderada a severa/
41
Abstracts: Poster
severa. Métodos: Se trataron pacientes con OG activa, 4 con
moderada/severa y 1 con severa. Esquema 1: metilprednisolona 500 mg y 250 mg semanales por ciclos de 6 semanas
cada uno. Esquema 2: metilprednisolona 1 g por día por 3
días consecutivos. Resultados: Cuatro hombres con OG
moderada-severa recibieron lo propuesto en el esquema 1: a)
uno realizó 2 ciclos con remisión completa; b) dos presentaron mejoría parcial y estabilización de la OG; c) un paciente
con fracaso previo a corticoides orales e intraoculares agravó
su oftalmopatía requiriendo cirugía. Una mujer con oftalmopatía severa y amenaza de pérdida de visión recibió lo propuesto en el esquema 2, con remisión total. Ningún paciente
recibió glucocorticoides oral posteriormente. Todos tuvieron
excelente tolerancia al tratamiento Un paciente presentó herpes zoster durante los pulsos semanales. Esto no se adjudicó
al tratamiento, por lo que se continuó con el mismo, con
excelente resolución del proceso viral. Conclusiones: La respuesta al tratamiento con corticoides EV en pulsos semanales
en OG moderada-severa fue exitosa y consistió en mejoría,
estabilización y/o remisión del cuadro en 3 de 4 pacientes.
En OG con amenaza de pérdida de la visión, el esquema de
altas dosis en días consecutivos fue altamente efectivo. El tratamiento fue seguro y bien tolerado en todos los casos.
Palabras clave: oftalmopatía de Graves; corticoides endovenosos; tratamiento.
PO032 OFTALMOPATÍA DE GRAVES: PREVALENCIA,
CLÍNICA Y FACTORES DE RIESGO
Zunino A1; Delfino L1; Ilera V1; Sapia V1; de Viale P;
Silva Croome MC1; Gauna A1 1
Hospital Ramos Mejía Introducción: La oftalmopatía de Graves (OG) representa la
manifestación extratiroidea más frecuente de la Enfermedad
de Graves (EG). Existen pocos datos disponibles de su prevalencia y características. Objetivos: Evaluar en nuestra población de EG que consultó por primera vez el servicio (2010):
presencia, actividad y gravedad de la OG; prevalencia de alteraciones en parámetros oftalmológicos; presencia de factores
de riesgo para OG. Métodos: Se efectuó el control de 47 a 102
pacientes: 42 mujeres, edad 45,6 ± 1,7años. Hipertiroideos
(38,3%), eutiroideos (57,6%) e hipotiroideos (2,1%). Se determinó TRAb (RIA), TSH, T4, T3 (Quimioluminiscencia).
Evaluación oftalmológica: Score de actividad Clínica y
Gravedad, Exoftalmometría, Presión intraocular, Agudeza
visual, Motilidad ocular. Análisis estadístico: test de MannWithney y exacto de Fisher. Resultados: La prevalencia de
OG clínica fue de un 55%: leve (54%), moderada (27%) y
severa (19%). El 58% reunió criterios de actividad. Se observó
alta prevalencia de proptosis (73%) y signos inflamatorios
(87%) a predominio de queratitis, edemas de carúncula y palpebral. Factores de riesgo: tabaquismo (40,4%); I131 previo
(19,1%); TRAb (80%); disfunción tiroidea (40,4%). Los valores de TRAb –estratificados según TSH normal o inhibido–
fueron significativamente más altos en esta población con OG
vs nuestra base de datos de EG. Conclusiones: Más de la mitad
de nuestra población presentó OG clínica, que, en la mayoría
de los casos, fue leve y activa. Los parámetros oftalmológicos
más comunes fueron la diplopía y los signos inflamatorios.
Tabaquismo y TRAb fueron los factores de riesgo más prevalentes. Estos resultados sugieren la importancia de la evaluación oftalmológica en todos los pacientes con EG.
42
Palabras clave: oftalmopatía de Graves; factores de riesgo;
evaluación oftalmológica.
PO033 TREATMENT OF GRAVES’ OPHTHALMOPATHY WITH
A PPAR-g ANTAGONIST AND COX-2 INHIBITOR (SODIUM
DICLOFENAC): A CRITICAL REVIEW
Mimura LY1; Moura JP1; Bloise W2
Hospital das Clínicas São Paulo Medical School; 2Graves’ Ophthalmopathy
Section Thyroid Unit Hospital das Clínicas São Paulo Medical School 1
Background: The long-term investigation of treatment of
Graves’ ophthalmopathy (GO) with sodium diclofenac was
not reported. Objective: The aim of this study is to show the
current evaluation and follow-up of sodium diclofenac in the
treatment of GO. Material and methods: Thirty-one patients
with GO were selected for this targeted treatment which started
in April 2006. Twenty-five finished the study and were assigned in 2 groups according to the clinical activity score (CAS):
Group I – CAS 5-7, n=6; Group II – CAS 2-4, n=25. The age of
patients ranged from 24 to 73 years-old. Oral diclofenac 50 mg
was administered every 12 hs, for 3 to 12 months. The drug was
withdrawn when the clinical signs and symptons disappeared
or when reached 12 months. Renal function was checked every
2 months. Patients with CAS 2 wereincluded when distressing
ocular pain and diplopia were remarkable complaints. Results:
The CAS of Group 1 decreased significantly from 6.3±0.81 to
4.1±1.6, p=0,023. The CAS of group 2 decreased but not significantly from 3.1±0.73 to 1.68±1.0 p=1.61. Hyperthyroidism
was not affected by sodium diclofenac in 14 of 15 patients.
Conclusion: The treatment of GO with sodium diclofenac was
more effective in ocular disease more active and not affected
the concurrent hyperthyroidism. These results should be validate by a controlled study in a greater number of patients.
Keywords: Graves’ ophthalmopathy; sodium diclofenac;
hyperthyroidism.
PO034 THE SYSTEM IGF-1/IGF-1 RECEPTOR AS A
PROBABLE LINK BETWEEN EUTHYROID GRAVES’
OPHTHALMOPATHY AND PAPILLARY THYROID CARCINOMA
Moura JP1; Monteiro MLR2; Mimura LY1; Siqueira SAC3; Dias EO4;
Nicolau W1; Bloise W1
1
Graves’ Ophthalmopathy Section/Thyroid Unit/Hospital das Clínicas, São
Paulo Medical School; 2Division of Ophthalmology/Hospital das Clínicas São
Paulo Medical School; 3Division of Pathology/Hospital das Clínicas/São Paulo
Medical School; 4Thyroid Unit/Hospital das Clínicas/São Paulo Medical School Background: Atypical euthyroid Graves’ ophtalmopathy (GO)
has been described but concurrent with papillary thyroid carcinoma is an unusual association. The link between these 2
atypical conditions is a matter of speculation. Objective:
To report 2 patients having these 2 uncommon findings
and describe a possible link between them. Material and
methods:The patients presented asymmetric proptosis, ocular
muscle restriction, eyelid retraction, diplopia and decreased
visual acuity. None of the patients showed clinical symptoms
or signs of thyroid disease, and both had normal laboratory
thyroid values, and negative thyroid antibodies. Both of them
had thyroid nodules harbouring papillary carcinoma treated by total thyroidectomy. Results: Immunohistochemical
analysis of the thyroid carcinomas revealed intense IGF-1
and IGF-1 receptor (IGF-1R) positivity in 1 specimen and
less intense IGF-1R positivity of the other patient specimen.
Histological scan of both thyroid glands was unable to detect
signs of autoimmune disease. Conclusion: The negativity of
Abstracts: Poster
antibody against TSH receptor and absence of histological
evidence of thyroid autoimmunity in patients with ocular
signs and symptoms similar to the GO and concurrent with
papillary thyroid carcinoma arouse the question of its pathogenesis and its linkage. By hypothesis the link between these 2
affections could be the system IGF-1/IGF-1R that is involved
in both diseases.
Keywords: Graves’ Ophthalmopathy; Euthyroidism; IGF-1/
IGF-1R System.
Thyroid and Pregnancy
PO035 PREGNANCY THYROID FUNCTION AT HOSPITAL
UNIVERSITARIO AUSTRAL
Urrutia MA1; Guerra JL1; Borracci R1; Alcoba Gutierrez ME1;
Fregonese R1; De Carli E1; Chazarreta D1; Patton NM1; Rojas M1;
Beruti E1Negueruela MC1
1
Hospital Universitário Austral (HUA) Background: Thyroid dysfunction has been proposed as a
maternal and fetal health risk during pregnancy. Objectives:
Our objectives were to determine thyroid dysfunction prevalence and the association with maternal and fetal complications at HUA. Methods: We retrospectively studied 4385
pregnant women during 2008-2012. We analyzed medical history (thyroid and obstetric) and thyroid function test values
within the first trimester of pregnancy. Statistical analysis was
done with the Chi-square test. Results: A total of 1013 first
time pregnant women were included. Median maternal age
was 30.2±5.9 years. Eight-hundred one (88%) women had
no previous thyroid disease. In this group, 738 (82.8%) were
euthyroid, 130 (14.5%) had subclinical hypothyroidism, 5
(0.56%) had overt hypothyroidism, and 18 (2%) were hyperthyroid. We also found 122 patients (12%) with a previous
history of thyroid disease: 109 (89.3%) were hypothyroid, 6
(5%) hyperthyroid and 7 (5.7%) had euthyroid nodular goiter.
A higher proportion of maternal fetal complications in hypothyroidism group was detected compared to the euthyroid
group (21.3% versus 15.3%, p=0.025).Gestational diabetes
was associated with pregnancy hypothyroidism (10.6% versus 5.1% in euthyroid, p=0.02). Conclusions: The prevalence
of total thyroid dysfunction in this population was 26%.
Obstetric-fetal complications were found increased in patients
with thyroid dysfunction. This phenomenon was observed
despite an optimal thyroid hormone replacement suggesting
other etiopathogenic factors. Regarding hypothyroidism, the
presence of increased first trimester TSH levels was clearly
related to gestational diabetes.
Keywords: pregnancy; thyroid function; gestational diabetes.
Thyroid Autoimmunity
PO036 DOENÇA TIREOIDIANA AUTOIMUNE E DIABETES
MELLITUS TIPO 1
Coelho ATM1; Rusch AS1; Schmitt-Lobe MC1
1
Ambulatório de Endocrinologia Pediátrica/Universidade Regional de
Blumenau (FURB) Introdução: O paciente com diabetes mellitus tipo 1 (DM1)
pode manifestar outras doenças autoimunes, dentre elas a
doença tireoidiana autoimune (DTA). O risco de desenvolvimento de DTA ao longo da vida, nesta população, é cerca
de 4 vezes maior que na população em geral. Seu diagnóstico é importante, principalmente em crianças, uma vez que
influencia no crescimento, no metabolismo de insulina, na
maturação puberal e na função gastrintestinal. Objetivo:
Determinar a frequência de DTA em 151 pacientes com
DM1. Métodos: As variáveis avaliadas foram: sexo, idade
cronológica (IC) no diagnóstico de DM1 e tempo entre
diagnóstico de DM1 e o diagnóstico de DTA. O diagnóstico
de DTA foi realizado pela dosagem de T4 livre e TSH. Caso
o TSH estivesse elevado, foram dosados os anticorpos antiTPO e anti-TG; se diminuído, Ac-anti-TRAB e ultrassom
de tireoide. Resultados: Noventa pacientes foram do sexo
feminino (F). A média da IC ao diagnóstico de DM1 foi de
97,56 meses. Tireoidite de Hashimoto (TH) ocorreu em 23
pacientes (21 F); nenhum paciente apresentou doença de
Graves. O tempo entre o diagnóstico de DM1 e DTA variou
de 4 a 144 meses (média = 65,58 meses) em 17 pacientes;
os demais não tinham data de diagnóstico de DTA precisa
e já estavam em tratamento quando admitidos no serviço.
Um paciente teve o diagnóstico de DTA antes do diagnóstico de DM1. Conclusões: Entre os pacientes com DM1,
15,23% apresentaram DTA. Houve grande variedade de
tempo entre o diagnóstico de DM1 e DTA, desde 4 meses
a 12 anos. Devido a isto, recomenda-se triagem rotineira da
função tireoidiana nestes pacientes.
Palavras-chave: doença tireoidiana autoimune; diabetes
mellitus tipo 1; intervalo de tempo.
Hyperthyroidism
PO037 A MORE THEN CAUSAL ASSOCIATION BETWEEN
GRAVES’ DISEASE AND MIASTHENIA GRAVIS
Schrank Y1; Correa ND; Braga N1
1
Hospital Federal de Bonsucesso (HFB) Introduction: The association between Graves’ disease and
miastenia gravis is not unusual and there may be a common genetic susceptibility in the 2 auto-immune disorders.
Recognizing the association of the 2 conditions is important
since these patients have a poorer prognosis. Case report:
T.F.V, 24 years, with known diagnosis of Graves‘ disease
reports eyelid weakness with worsening later in the day,
rapidly progressive muscle weakness with significant functional impairment, and dysphagia to solids. On examination
we noticed a diffuse goiter, tremors, silky and warm skin,
and bilateral ptosis with impaired ocular motility and decreased muscle strength which was more pronounced in the
proximal segment of the lower limbs. Since the association
of diffuse toxic goiter and myasthenia gravis was considered, the determination of anti-acetylcholine receptor was
done and resulted positive. The remaining laboratory studies were unremarkable apart from abnormal thyroid function tests. Discussion: The reported prevalence of myasthenia in hyperthyroid patients is around 0.35%, prevalence
about 30 times greater than the general population. In turn,
the prevalence of hyperthyroidism in series of patients with
myasthenia gravis ranges between 2% to 17% compared
with a 1 in 10 000 prevalence in the general population. In
half the cases the thyroid hyperfunction precedes myasthenia. Conclusion: The association of hyperthyroidism and
muscle weakness is relatively common and the coexistence
of myasthenia should be considered especially in patients
with hyperthyroidism who present acute weakness, ptosis
and bulbar muscle involvement.
43
Abstracts: Poster
Keyword: Graves’s disease; myasthenia Gravis; auto-immune
disorders.
PO038 SEVERE HEPATITIS RELATED TO GRAVES’ DISEASE
CONTROLLED WITH ANTITHYROID DRUGS: CASE REPORT
Amaral SS1; Macedo LML1; Alcantara ANS1; Silva PSA1; Costa MCM1;
Ferraz TMBL1
1
Hospital Geral de Fortaleza (HGF) Background: Severe hepatitis in the clinical setting of
Graves’ disease is quite rare and is usually attributed to the
increased metabolic demand and relative hypoxia during
thyrotoxicosis. Objectives: To report a case of a patient with
Graves` disease who presented severe hepatitis controlled
with antithyroid drugs. Methods: Medical record analysis
of a patient hospitalized in the Clinical Unit of the HGF,
Ceará, Brazil. Results: A 37-year-old Brazilian female presented with weight loss, abdominal pain, nausea, vomits
and jaundice. Physical examination: tachycardia, jaundice
(3+/4+), systolic mitral murmur (3+/6+), fine tremor in the
hands, mild exophthalmos, without thyroid enlargement.
Laboratorial data: suppressed TSH with FT4>6 ng/dL (normal, 0.89-1.80); positive TPOAb and TRAb; marked elevation of liver transaminases (>10 times the upper limit of
normal – ULN), and bilirubin (>5 times ULN). Investigation
for viral and autoimmune hepatitis, Wilson’s disease, hemachromatosis was negative. Other tests: normal echocardiogram; thyroid ultrasonography: changes in the echogenicity;
thyroid scintigraphy: diffuse goiter with increased uptake;
liver biopsy: necrosis in the zone 3, venous congestion and
discrete inflammatory process. Propranolol, prednisone
and metimazol were initiated with daily assessment of liver
function and an important improvement of symptoms and
transaminases levels afterwards. We decided by radioiodine
after thyroid hormones decrease. Conclusions: Graves’ disease may attend with peculiar presentation of severe hepatitis
without thyroid enlargement and significant exophthalmos.
Antithyroid drugs may be a good therapeutic option for initial management of Graves’ hepatitis if transaminases levels
can be closely monitored.
Keywords: hepatitis; Graves’ disease; hiperthyroidism.
PO039 ASSOCIAÇÃO DE DOENÇA DE GRAVES E HEPATITE
AUTOIMUNE
Maia CP1; Corrêa MV1; Santos JCV1; Magalhães RSC1; Reis MDSL1;
Tonet C1; Messias ACNV1; Mansur VAR1
1
Hospital Federal dos Servidores do Estado do Rio de Janeiro (HFSERJ) Objetivo: A disfunção hepática na doença de Graves possui diferentes etiologias, cujo esclarecimento é fundamental
para uma adequada terapêutica. Métodos: Relatamos um
caso de associação entre doença de Graves e hepatite autoimune, com revisão literária nas bases de dados Pubmed.
Resultados: Paciente do sexo feminino, 53 anos, com hipertireoidismo prévio há 18 anos, tratada com metimazol e diante
de falência terapêutica, submetida à tireoidectomia parcial.
Adentrou nosso serviço francamente sintomática, já tendo
utilizado metimazol por 2 meses, suspenso por colúria. Ao
exame físico, apresentava-se hipertensa, taquicárdica, com
bócio difuso, oftalmopatia CAS: 2 e edema periférico. Exames
evidenciaram TSH suprimido, T4 livre de 2,1ng/dL, transaminases elevadas, colestase, insuficiência hepática, hematúria e captação de iodo aumentada. Os exames da internação
44
revelaram fator antinuclear (FAN) reagente, imunoglobulinas
elevadas, anticorpos antimitocôndria, anti-LKM1 e antimúsculo liso normais, mantendo alterações laboratoriais mesmo
após meses sem metimazol. A biópsia hepática revelou histopatológico compatível com hepatite autoimune. Recebeu
dose terapêutica de iodo, com profilaxia para oftalmopatia.
Discussão: A coexistência entre doenças autoimunes como
tireoidopatias e hepatite autoimune é relativamente comum,
podendo ocorrer em 6% na doença de Graves e 12% na
tireoidite de Hashimoto. Portadores de hepatite autoimune
apresentam até 40% de prevalência de associação com patologias de etiologia semelhante. As principais são cirrose biliar
primária, colangite esclerosante, seguidas de tireoidopatias
autoimunes em 10% dos casos. Conclusão: Relatamos caso
de doença de Graves e hepatite autoimune, excluídas outras
causas de insuficiência hepática, com melhora clínico-laboratorial após corticoterapia. Ressaltamos a importância de
estudos sobre alterações hepáticas no hipertireoidismo para
definir a melhor conduta nesses casos.
Palavras-chave: hepatite autoimune; doença de Graves;
hipertireoidismo.
Hypothyroidism
PO040 PREVALENCE OF HYPOTHYROIDISM IN PATIENTS
WITH FROZEN SHOULDER
Shiefer M1; Teixeira PFS1; Castro O2; Silva NAO1; Conceição FL1
1
Universidade Federal do Rio de Janeiro (UFRJ); 2Universidade Federal do Rio
de Janeiro (UFRJ)/Santa Casa da Misericórdia (SCMRJ) Objectives: This study aimed to determine the prevalence
of hypothyroidism and circulating anti-thyroperoxidasis
antibodies (TPO-Ab) in patients with frozen shoulder (FS)
and to assess if those subjects are at higher risk for hypothyroidism. Patients and methods: A case control study
was performed to compare FS patients (cases) and patients
attended at an orthopedic service for other clinical conditions (controls). FS was diagnosed according to specific
criteria: reduced shoulder movement amplitudes (goniometric manual measurement), and rigid shoulder without
crepitating, instability or reduction of strength. A normal
radiographic exam of shoulder was necessary and subjects
with previous shoulder fracture or surgery were excluded.
Specific questionnaire and measurements of serum TSH,
FT4 TPO-Ab were performed. Results: Seventy-four FS
patients and 88 controls with similar mean age (56 and 52
years, respectively) were evaluated. Female gender was more
frequent in FS (71.6% versus 55.7%; p=0.02). The prevalence
of hypothyroidism diagnosis (previously done or at study
inclusion) was slightly higher in FS (16.2% versus 8.0%;
p=0.07). However, the majority of FS hypothyroid subjects
had already this diagnosis before study inclusion (14.9% of
FS versus 2.3% of control subjects [p=0.003]). Positive circulating TPO-Ab was not more prevalent in FS (18% versus
14.6%; p=0.43). Multivariate analysis detected that female
gender was the only independent variable associated with
FS and that the risk of hypothyroidism was related to the
higher prevalence of women in this group. Conclusion:
Hypothyroidism was more frequently diagnosed in FS
patients, however it was not an independent condition associated with this orthopedic disease.
Keywords: hypothyroidism; autoimmunity; frozen shoulder.
Abstracts: Poster
Hyperthyroidism
PO041 IMPLICATIONS OF INTERATRIAL SEPTUM
ABNORMALITIES AMONG HIPERTHYROID PATIENTS WITH
ATRIAL FIBRILLATION – A CROSS SECTION ANALYSIS WITH
TRANSOESOPHAGEAL ECHOCARDIOGRAPHY
Souza MV1
Instituto Estadual de Diabetes e Endocrinologia Luis Capriglione (IEDE)
1
Background: Hyperthyroidism is a questionable risk factor for
thromboembolism among patients with atrial fibrillation (AF)
and interatrial septum abnormalities (ISA) have been associated with cryptogenic stroke especially among young patients,
although its prevalence among hyperthyroid patients have never
been addressed.1,2 Objective and methods: As our group conducts a transoesophageal echocardiography (TOE) based treatment in every patient with AF related to hyperthyroidism3, the
aim of this study is primarily describe the incidental findings
of ISA and discuss how it may affect the type of thromboprophylaxis. Forty-four patients between 18-65 years, without
structural valve disease, with hyperthyroidism regardless of
an etiology and associated with AF were selected. Results: ISA
were present in 10/44 (22.7%) patients, 8 with patent foramen
ovale (PFO),3 with atrial septum aneurysm (ASA) and 1 with
both present concurrently. Three of 8 (37.5%) and 1/3 patients
(33.3%) with PFO and ASA, respectively, did not meet clinical criteria for oral anticoagulation other than acetyl salicylic
acid. Conclusions: The knowledge of these ISA may be useful
not only to guide the appropriate thromboprophylaxis among
patients that would be `missed` by clinical criteria but also
direct appropriate treatment after a possible reversal to sinus
rhythm. Therefore TOE diagnosis of PFO and ASA may add
useful information to hyperthyroid patients with AF. References: 1. Singer DE et al. Chest. 2008; 133:546S-592S. 2. Mas JL et al. N Engl J Med. 2001; 345:1740-6. 3. Souza MV et al. Clin Endocrinol (Oxf). 2012; 76:448-53.
Keyowrds: heart septal defects; atrial; hyperthyroidism; atrial
fibrillation.
Hypothyroidism
PO042 FOREARM BLOOD FLOW IN WOMEN WITH
SUBCLINICAL HYPOTHYROIDISM
Ghetti FF1; Lacerda RP1; Werneck FZ2; Coelho EF2; Teixeira PFS2;
Vaisman M2; Lima JRP1; Laterza MC1 1
Cardiovascular Research Unit and Exercise Physiology/University Hospital
and Faculty of Physical Education and Sports/Federal University of Juiz de
Fora; 2Endocrine Clinic/University Hospital Clementino Fraga Filho/Federal
University of Rio de Janeiro
Background: Forearm blood flow has been considered prognostic marker in heart failure patients. However, it has been
poorly described in patients with subclinical hypothyroidism
(SH). Objective: Investigate the integrity of forearm blood
flow in patients with SH. Methods: Fifteen non diabetic,
without medication, with SH and age (38±12 versus 40±9
years-old, respectively, p=0.57), BMI-matched (27±5 kg/m2
versus 26±5 kg/m2, respectively, p=0.63) and healthy women
were involved in the study. The blood pressure was measured
by automatic and oscillometric cuff (DIXTAL®) and forearm
blood flow measured by the method of venous occlusion plethysmography (Hokanson®). These variables were recorded
simultaneously for 3 minutes of rest in the supine position.
Forearm vascular conductance was calculated by dividing
forearm blood flow by mean arterial pressure and multiplied
by 100. The comparisons between groups were analyzed
using non-paired Student’s t-test. Significant differences were
considered to be at p<0.05. Data are presented as mean±SD.
Results: TSH levels (7.3±3.1 versus 2.4±0.9 mUI/mL,
p<0.001) and anti-TPO (238.3±371.5 versus 0.3±0.2 IU/mL,
p=0.026) were significantly higher in patients with SH when
compared with healthy individuals. FT4 levels were similar
between patients with SH and healthy individuals (0.98±0.16
versus 1.02±0.11 ng/dL, respectively, p=0.441). Regarding the
hemodynamic values of mean arterial pressure (86±6 versus
88±10 mmHg, p=0.643), forearm blood flow (2.38±0.76 versus 2.51±1,09 mL/min/100 mL, p=0.699) and forearm vascular conductance (2.75±0,90 versus 2.91±1.17 units, p=0.703)
were similar between patients with SH and healthy individuals, respectively. Conclusion: These findings suggest that the
forearm blood flow is preserved in patients with SH.
Keywords: plethysmography; hypothyroidism; blood pressure.
PO043 AVALIAÇÃO DO ESPESSAMENTO MÉDIO-INTIMAL
DE CARÓTIDAS EM PACIENTES COM HIPOTIREOIDISMO
SUBCLÍNICO, COM OU SEM SÍNDROME METABÓLICA
França MM1; Hueb JC1; Padovani CR1; Nogueira CR1; Mazeto GMFS1
Botucatu Medical School, Sao Paulo State University – UNESP 1
Introdução: A síndrome metabólica (SM) se constitui em um
conhecido fator de risco para doença cardiovascular (DCV).
Recentemente, alguns estudos têm relatado a associação entre
hipotireoidismo subclínico (HSC) e aumento desse risco. A
medida da espessura médio-intimal das carótidas (EIM) por
ultrassonografia é capaz de detectar alterações iniciais da aterosclerose, podendo predizer o risco de DCV. Objetivo: O
objetivo deste estudo é comparar a EIM em pacientes com
HS, com e sem SM. Pacientes e Métodos: Foram avaliados 32
pacientes com HSC, sendo subdivididos em 2 grupos: com e
sem SM, segundo os critérios da Federação Internacional de
Diabetes. Houve um grupo controle de pacientes eutireoidianos (n=31), que também foram subdivididos quanto à presença ou não de SM. Foram comparados quanto às EIMs média
e máxima, ao gênero, idade, dados comportamentais, histórico
de DCV, medidas antropométricas, pressão arterial, glicemia
de jejum, colesterol total, LDL, HDL, triglicérides, tireotrofina
(TSH) e tiroxina livre (T4 livre). Resultados: Comparando-se
os grupos com HSC, as EMIs média e máxima foram maiores
no grupo com SM do que no sem SM [0,59±0,10 mm versus
0,73±0,19 (p< 0,05) e 0,69±0,15 mm versus 0,86±0,21 (p< 0,05),
respectivamente]. Comparando-se os grupos com SM, o grupo
com HSC apresentou maior EIM máxima do que o eutireoidiano (0,86±0,21 mm versus 0,74±0,17, p< 0,05). Conclusões:
Neste estudo, o grupo com HSC e SM apresentou maiores EIM
média e máxima do que o HSC sem SM. A EMI máxima também foi maior no grupo com HSC e SM do que no grupo com
SM em eutireodismo.
Palavras-chave: hipotireoidismo; síndrome x metabólica;
ultrassonografia Doppler.
PO044 OXYGEN UPTAKE KINETICS ARE SLOWED IN
SUBCLINICAL HYPOTHYROIDISM
Werneck FZ1; Coelho EF1; Lima JRP2; Laterza MC2; Bonfante HLM3;
Barral MM3; Teixeira PFS1; Vaisman M1
1
Endocrine Clinic/University Hospital Clementino Fraga Filho/Federal
University of Rio de Janeiro; 2Faculty of Physical Education and Sports/Motor
Assessment Laboratory/Federal University of Juiz de Fora;3Faculty of Health
and Medical Sciences of Juiz de Fora (SUPREMA) 45
Abstracts: Poster
Dynamic response of oxygen uptake at onset and recovery
of exercise (VO2 kinetics) in patients with subclinical hypothyroidism (SH) is unknown. The aim was to compare the
VO2 kinetics during and after a constant-load exercise in SH
patients. A total of 19 women with HS (TSH=6.9±2.9 mUI/mL;
T4=0.97±0.15ng/dL) and 19 health controls (TSH=2.3±0.9
mUI/mL; T4=0.99±0.11ng/dL) performed 3 transitions of 6
minutes of 50W constant work rate exercise followed by 6
minutes of recovery on a cycle ergometer. Ergospirometry
was used to evaluate VO2 (Cosmed K4b2). The time constant
of VO2 kinetics (tVO2) was determined by monoexponencial
function, using a 5-point moving average of the breath-bybreath data. The tVO2 is the time corresponding to 63% of
the total VO2 response fitted from exercise onset or recovery. Student’s t-test and Pearson’s r correlation were used.
There was no difference between patients and controls in
age (39.6±11.4 versus 39.1±8.4 years), BMI (26.1±5.9 versus 26.5±5.6 kg/m2), physical activity level (6.80±1.55 versus
7.60±1.21) and VO2 steady-state response (1019±123 versus
993±92 mL/min), respectively. However, the time constants
for the VO2 on-transients (47.1±8.0 s versus 39.9±6,4 s,
p=0.004) and VO2 off-transients (54.3±6.5 s versus 44.3±6.1
s; p=0.001) was significantly prolonged in SH compared with
controls. Higher values of O2 deficit (580±102 vs. 477±95
mL; p=0.003) and O2 debit (679±105 mL versus 572±104
mL; p=0.003) were found for SH patients. TSH levels showed a positive correlation with tVO2on (r=0.52; p=0.001)
and tVO2off (r=0.57; p=0.001). These data demonstrate that
VO2 kinetics is slowed in SH.
Keywords: VO2 kinetics; subclinical hypohtyroidism; submaximal exercise.
PO045 CASE REPORT: SEVERE HYPOTHYROIDISM
LEADING TO CONGESTIVE HEART FAILURE.
Mastella LS1; Almeida SL1; Borges AP1; Bodanese LC1; Reppetto G1
1
Pontifícia Universidade Católica/Rio Grande do Sul (PUC/RS) Female, 20 years, admitted to Hospital São Lucas, because of
decompensated congestive heart failure. She had a history
of dyspnea on moderate exertion, progressive, in the last 10
months and appearance of orthopnea and paroxysmal nocturnal dyspnea in the last month. She had also lower limb
edema since the onset of symptoms. In the first evaluation,
was in good general condition, but in anasarca. Had minimal crackles in both lung bases and showed no hepatomegaly.
Was noted the facies mixedematosa. Among the initial examination, chest radiography showed cardiomegaly with signs
of pulmonary congestion. Echocardiography showed eccentric ventricular hypertrophy with increased LV and diffuse
hypokinesis, EF of 28%, and moderate pericardial effusion
without signs of increased intrapericardial pressure. There
was no significant valvular dysfunction. Blood exams showed
severe hypothyroidism with TSH>100 mU/L. However, the
markers of thyroid autoimmunity were negative: ACAntiTPO 18.8 (VR<35.5) and ACAnti-Thyroglobulin<20 IU/
mL (NR<40). Evolution: Was initiated levothyroxine 25
mcg/day. The dose was increased gradually until 100 mcg/
day. In return, there was significant clinical improvement.
Echocardiography also showed improvement, with an ejection fraction of 45.8% and a reduction of pericardial effusion.
At this time the dose of levothyroxine was increased to 125
mcg/day. Discussion: Dilated cardiomyopathy is charac-
46
terized by dilatation and impaired contraction of 1 or both
ventricles and the affected patients have systolic dysfunction
(ejection fraction<40%). Hypothyroidism is a rare cause of
this situation and the exact mechanism of disease development is not yet well established.
Keywords: thyroid; heart failure; dilated cardiomyophaty.
PO046 DOSIS SUSTITUCIÓN TIROIDEA CON L-TIROXINA
EN HIPOTIROIDISMO PRIMARIO SEGÚN ETIOLOGÍA Y
VOLUMEN TIROIDEO
Munizaga F1
Hospital Clínico San Borja-Arriarán. Universidad de Chile 1
Introducción: Dosis recomendada de 1,5 a 1,7 ug/kg peso
de L-T4. Material y Métodos: Estudio prospectivo de 632
pacientes de más de 2 años de evolución, diagnosticados con
TSH >10 mU/L y T4 libre <0,8 ng/dL. Definiciones: Postquirúrgicos (PQ) antecedentes de tiroidectomía total
por patología benigna Post-I131 (PR) por hipertiroidismo. Tiroiditis crónica (TCA) anticuerpos(+) y/o ECO con
pattern 3. Primaria (P) anticuerpos(-) y ECO pattern 1. ECO:
volumen grande (g) >10 mL, normal (n) 5-10 mL y pequeño
(p) <5 mL y midió. remanente, <1 cm: sin remanente (r). Se
utiliza L-tiroxina, se miden 2 TSH separada por intervalo >6
meses. Objetivo terapéutico 0,5-4 mU/L de TSH. Criterios
de exclusión: embarazo (E), cambio peso >4 kg, estar fuera
de rango, uso de fármacos. Resultados: 136 excluidos.
Seleccionados 496, hombres 49 (9,9%), mujeres 447 (90,1%) ETIO Y ECO n EDAD LT4 (dosis: ug/kg) PQ s/R 68 47,2±15,3 1,63±0,36 PQ c/R 21 50,1±13 1,33±0,31 (a) PR 20 47±14,3 1,47±0,4 (a) TCA (g) 57 37±14,8 (d) 1,23±0,4 (a,b) TCA (n) 119 43,8±13 1,22±0,34 (a,b) TCA (p) 150 48,9±13,3 1,35±0,34 (a,b) P (n) 20 40,2±16,3 (d) 1,06±0,3 (a,b) P (p) 41 49,6±12,6 1,13±0,29 (a,b) TOTAL 496 45,8±14,3 1,31±0,28 p< 0,01:(a) con respecto al grupo PQ s/R , (b) con respecto
al grupo PR, (c) con respecto M c/TE y (d) con respecto a la
edad con otros grupos. Conclusiones: La dosis de sustitución establecida en pacientes hipotiroideos es menor y depende de la etiología y del
volumen tiroideo, siendo mayor significativamente en postquirúrgicos sin remanentes, post-radioyodo.
Palabras clave: hipotiroidismo; dosis l-tiroxina; etiología.
PO047 AVALIAÇÃO DO SERVIÇO DE REFERÊNCIA
EM TRIAGEM NEONATAL NO ESTADO DE TOCANTINS
(SRTN-TO) NO PERÍODO DE 2007 A 2011
Alves ARV1; Cruz MA2; Oliveira BS2; Nascimento SAR2; Araújo CMXB2;
Alves Jr AM1
1
Secretaria Estadual de Saúde de Tocantins (SESAU); 2Associação de Pais e
Amigos do Excepcionais (APAE)
Introdução: O Programa Nacional de Triagem Neonatal
(PNTN) tem como objetivo a detecção precoce do hipotireoidismo congênito (HC) assintomático, levando ao tratamento
precoce e prevenindo sequelas neuropsicomotoras. A APAE
de Araguaína (TO) é credenciada na SRTN/TO desde a criação do PNTN em 2001. Objetivo: Avaliar dados do SRTN-TO
do período de 2007 a 2011 e estabelecer a evolução dos
índices de cobertura, incidência, tratamento e acompanha-
Abstracts: Poster
mento dos casos de HC nesse período. Material e métodos:
Realizado estudo transversal utilizando dados conjugados do
Sistema de Informação sobre Nascidos Vivos do Tocantins
(SINASC/TO) e formulários indicadores do PNTN/MS dos
anos de 2007 a 2011. Resultados: Os anos de 2007 a 2011
apresentaram respectivamente os seguintes índices: cobertura dos recém-nascidos (RNs) vivos (96,2%; 82,8%; 86,5%;
82,2%; 84,2%), incidência de HC entre os RNs vivos (1:2.763;
1:5.205; 1:4.664; 1:4.045; 1:3.069), RNs triados com idade
até 7 dias (28,7%; 28,68%; 29,43%; 31%; 37%), idade média
dos casos na primeira consulta no SRTN (73, 86, 63, 57, 66
dias), porcentagem dos casos em acompanhamento regular no SRTN/TO (77%; 97%; 90%; 89%; 99%). Conclusões:
Apesar do aumento dos índices de cobertura e da redução
dos intervalos de tempo das etapas de triagem, convocação e
tratamento no SRTN/TO, observa-se que esses prazos estão
acima das metas do PNTN. Destaca-se, no SRTN/TO, uma
população rural flutuante, rotatividade da equipe de saúde e
munícipios pequenos com sistema de saúde pública e logística incipiente, dificultando a implementação das metas preconizadas.
Palavras-chave: hipotireoidismo; triagem neonatal; Tocantins.
PO048 DETERMINING THE TSH REFERENCE VALUE:
EXPERIENCE FROM THE CHILEAN NATIONAL HEALTH
SURVEY 2009-2010
Mosso L1; Margozzini P1; Solari S1; Dominguez MA1; Arteaga E1
1
Pontificia Universidad Catolica de Chile Objective: Exploring alternatives to establish reference values
for TSH based on population data. Methods: The Chilean
2009-2010 health survey includes 5416 subjects representing
the total population. TSH was measured in 2785 participants.
Median and percentiles 2.5 and 97.5 for TSH value in 3 populations were calculated: the “total”, the “non thyroid history”,
and the “non thyroid background or TPO positive”. Taking
the 97.5 p values, it was estimated the percentage of hypotiroidism in Chile, and then it was compared with the percentage calculated in accordance with laboratory kit (Roche:
0.3 to 4.2 UI/mL). Results: Population without background:
2493 subjects, without background or TPO positive: 2177.
For these 3 populations with p=2.5 TSH value was: 0.59; 0.83
and 0.76, median value: 2.52; 2.49 and 2.4, for 97.5 p value:
9.71, 7.46 and 6.88, respectively. The percentage of the total
population that would have hypothyroidism based on 97.5
p of each subpopulation varies from: 2.54%; 4.9% and 5.9%
and reaches 19.4% according to kit laboratory. Conclusion:
Cataloguing hypothyroid is absolutely dependent on the TSH
cut-off point used. The 97.5 p of any of our population used
as reference is superior to the lab kit delivered. We must look
more deeply at the criteria used to define the normal value of
TSH we use in our countries.
Keywords: TSH; hypothyroidism; normal values.
PO049 ADESÃO AO TRATAMENTO DE HIPOTIREOIDISMO
NO AMBULATÓRIO UNIVERSITÁRIO DE REFERÊNCIA DA
UNIVERSIDADE REGIONAL DE BLUMENAU/SC
Thomazelli FCS1; Weissenberg C1; Augusto SB1
1
Universidade Regional de Blumenau (FURB) Introdução: O tratamento de escolha para o hipotireoidismo
consiste na reposição hormonal diária de levotiroxina sódica
em dose única, via oral. A falta de adesão é tida como um impe-
dimento ao alcance dos objetivos terapêuticos, podendo levar
a uma série de complicações. Objetivos: Os objetivos do trabalho são quantificar a adesão ao uso de levotiroxina na abordagem de hipotireoidismo no Ambulatório Universitário de
Referência, em Blumenau, e correlacionar variáveis demográficas e as referentes ao tratamento medicamentoso. Métodos:
Estudo transversal realizado com 63 pacientes maiores de 18
anos em uso contínuo e regular do medicamento para tratamento de hipotireoidismo. Para o estudo, foram feitas entrevistas, utilizando-se o questionário de Morisky Green Levine,
padronizado para quantificação da adesão terapêutica e as
demais variáveis: idade, sexo, tempo de diagnóstico, tempo
de estudo, renda financeira, causas do hipotireoidismo, especialidades farmacêuticas e forma de obtenção das mesmas, as
quais foram coletadas através de perguntas complementares
produzidas pelos autores. Resultados: A maioria da amostra foi do sexo feminino (84,1%), com faixa etária predominante entre 41 e 60 anos (47,6%). A etiologia mais apontada
foi hipotireoidismo primário (69,8%). A maioria da amostra
obtém sua medicação através do Sistema Único de Saúde
(SUS) e 53,9% dos pacientes da amostra foram aderentes ao
tratamento. Conclusão: A adesão terapêutica foi estatisticamente significante quando relacionada à renda financeira
(p=0,009), forma de obtenção da especialidade farmacêutica
(p=0,03) e hipotireoidismo causado por tireoidectomia por
nódulo (p=0,01) e câncer (p=0,02) tireoidianos.
Palavras-chave: hipotireoidismo; adesão; terapêutica.
PO050 CARCINOMA PAPILÍFERO DE TIREOIDE: RELATO DE
2 CASOS COM EVOLUÇÃO INESPERADA
Corrêa ND1; Schrank Y1; Araujo NBC1; Netto IG1
1
Hospital Federal de Bonsucesso (HFB) Introdução: O carcinoma diferenciado de tireoide apresenta
boa evolução clínica, com sobrevida longa quando precocemente diagnosticado. Relatamos 2 casos de carcinoma
papilífero de tireoide com estratificação de risco diferentes
e evolução pouco habitual. Caso 1: L.F.V, sexo feminino, 31
anos, tireoidectomizada em 1976 por bócio nodular, com
diagnóstico de carcinoma papilífero com metástases pulmonares assintomáticas. Foi encaminhada à radiodoterapia,
mas abandonou o tratamento. Em 2002, procurou serviço de
emergência com dispneia e radiografia de tórax evidenciando
imagens nodulares pulmonares. Biópsia pulmonar diagnosticou carcinoma metastático de tireoide sendo a paciente
encaminhada para radioiodoterapia. A tireoglobulina se
manteve elevada, e espirometria de controle mostrava piora
do quadro pulmonar, inviabilizando nova dose terapêutica.
Permanece com quadro clínico estável, níveis decrescentes de
tireoglobulina e anticorpo antitireoglobulina elevado. Caso
2: C.D, sexo feminino, 63 anos, submetida à tireoidectomia
por bócio nodular em 2005, com diagnóstico de carcinoma
papilífero variante folicular, com êmbolos neoplásicos linfáticos e venosos, seguida de radioiodoterapia (100 mCi). A
pesquisa de corpo inteiro (PCI) de controle foi negativa, e
os níveis de tireoglobulina indetectáveis até 2011, a partir de
quando aumentaram significativamente. Nessa ocasião, a PCI
e a ultrassonografia cervical eram normais. Apresentou dor
em coxa esquerda, com radiografia mostrando área lítica em
fêmur. Submetida à osteossíntese com biópsia óssea confir-
47
Abstracts: Poster
mando implante metastático. Encaminhada para radioiodoterapia. Discussão: O acompanhamento regular e em longo
prazo dos pacientes com câncer papilífero de tireoide permite
modificar a estratificação de risco de acordo com a evolução
e ajustar a abordagem terapêutica.
Palavras-chave: carcinoma papilífero; tireoide; evolução.
PO051 PROPHYLACTIC NECK DISSECTION IN DTC. IS IT
WORTH IT?
Volpi EM1; Omokawa M1; Bertelli AAT2; Massarollo LCB3; Steck JH4;
Cernea CR1
1
University of São Paulo;2Faculdade de Ciências Médicas da Santa Casa de São
Paulo;3 Hospital São Christovão;4Hospital Mario Gatti Background: The incidence of lymph node (LN) metastasis
in cases of well-differentiated thyroid carcinoma (WDTC)
has a wide range of incidence reported. Controversy still
remains regarding whether LN dissection needs to be performed at the time of thyroidectomy. Objectives: Determine
if the implementation of prophylactic neck dissection of the
central compartment as a routine procedure increases the risk
of injury over the recurrent laryngeal nerve and parathyroid
glands improves the efficacy of surgery and could avoid the
need of Radioiodine therapy. Methods: Retrospective cohort
study of 59 patients undergoing to total thyroidectomy plus
prophylactic central node dissection for papillary cancer with
pre-operative staging T1 and T2 N0 (>1 cm) from March 2008
to July 2012. The outcomes were compared to 162 patients
in the same conditions and period undergoing conventional
treatment. Results: There is no statistical difference of vocal
fold injury in both groups but regarding the numbers of
hypoparathyroidism it was statistically significant (p<0.005).
In cases with no node metastasis the radioiodine therapy was
not indicated for all cases usually when the pathologic features upstaged the final staging. However when nodal metastasis were found the dose of 131-I was higher (at least 100
mCi). Conclusion: Even though the prophylactic dissection
did not cause a statistically significant increase in injuries on
the recurrent laryngeal nerve, its realization is associated with
high rates of hypoparathyroidism in our series. The advantage
could be a better oncological evaluation and the possibility to
avoid radioiodine therapy in some cases.
Keywords: neck dissection; thyroid cancer; complications of
surgery.
PO052 IMPACT OF TUMOUR SIZE IN THE OUTCOME OF
PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA
BASED ON A SERIES OF 218 CASES
Gonçalves Filho J1; Quiroa LR1; Kowalski LP 1
Hospital AC Camargo Background: The papillary thyroid microcarcinoma (PTMC)
is defined as a tumor measuring ≤10 mm in diameter and usually associated with an excellent prognosis. However, age >45
years is considered an indicator of poor prognosis. Objective:
The objective of this study was to evaluate the influence of
tumor size in the outcome of patients with papillary thyroid
microcarcinoma and with age >45 years. Patients and
Methods: A retrospective study with 218 patients treated
between 1980 and 2007 in a single institution was performed.
There were 30 male and 188 women with a median age of
52 years. Total thyroidectomy was the surgical procedure in
196 (90%) patients and partial thyroidectomy in 22 (10%).
48
Adjuvant ablative dose or radioiodine was used in 93 (42.7%)
patients. Results: Eighty and nine (40%) patients had tumor
size with <5 mm and 129 (60%) had tumors ranging in size
from 6 mm to 10 mm. Histopathologic lymph node metastasis was present in 1 (0.5%) patient with tumor <5 mm and
12 (5.5%) patients with tumors >5 mm. Univariate analysis
showed that size of the tumor >5 mm was significantly correlated to multifocal disease (p=0.025) and pN+ (p=0.012).
In contrast, distant metastasis, extrathyroidal extension, lymphatic and vascular invasion showed no statistical correlation. However, neck recurrence was significantly associated
with lymphatic invasion (p=0.001). Conclusion: PTMC has
an excellent prognosis, but tumor size >5 mm is associated
with multifocal and lymph nodal involvement.
Keywords: thyroid carcinoma; papillary; microcarcinoma.
Multinodular Goiter
PO053 TRATAMIENTO DE BOCIOS MULTINODULARES
MIXTOS CON I-131 E INYECCIONES DE ETANOL EN FORMA
COMBINADA
Jara Yorg JA1; Jara MA; Jara Ruiz JM; Jara Ruiz ED1 1
CEDIN, Centro de Diagnóstico y Tratamiento Nuclear, Centro
Endocrinológico y Diagnóstico por Imagen Antecedentes: Los nódulos pueden ser únicos o múltiples.
Los palpables tienen una prevalencia del 4%-7% en las mujeres y del 1% en los hombres que viven en sitios con suficiencia
de iodo. Objetivos: Tratar pacientes con bocios multinodulares mixtos hipercaptantes con I131 e inyecciones de etanol.
Métodos: Presentamos 80 pacientes con hipertiroidismo
multinodular, diagnosticados clínicamente con dosaje de
hormonas tiroideas, ecografía y centellografía de tiroides. A
dichos pacientes se les realizó una punción biopsia de tiroides
bajo pantalla ecográfica. Todos los resultados dieron negativo
para las células atípicas. Los pacientes atendidos en el CEDIN
desde octubre de 2010 a mayo de 2011 e eran portadores de
nódulos mixtos. 58 eran del sexo femenino y 22 del sexo masculino. Todos con edades comprendidas entre 18 y 68 años,
siendo que la edad promedio era de 38 años. Los pacientes
fueron tratados con I131 por vía oral, con una dosis promedio de 25 mCi (925 mBq). Además, todos fueron tratados con
inyecciones de etanol etílico al 98% + mepivacaína al 3% sin
epinefrina. Se utilizó un ecógrafo General Electric Vivid E, con
un transductor de 5-12 MHz lineal. Las gammagrafías tiroideas se realizaron con una gammacámara Spect Mediso, utilizando el Pinhole. Resultados: El 88% de los pacientes logró
una reducción del 90% de los nódulos. Conclusiones: Los
bocios multinodulares hipercaptantes pueden ser tratados
con la terapia combinada del I131, por vía oral, y por la adición de inyecciones de etanol + mepivacaína, que reducen en
mayor medida el volumen de los nódulos.
Palabras clave: nódulos; I-131; etanol.
PO054 RELAÇÃO BÓCIO MERGULHANTE E SÍNDROME
DA VEIA CAVA SUPERIOR
Leão JRB1; Ribeiro RX1; Normanha LL1; Vento L1
Pontifícia Universidade Católica de Goiás (PUC/GO) 1
Introdução: O bócio mergulhante (BM) é uma afecção da
tireoide com aumento de volume invadindo a cavidade torácica através do estreito superior do tórax. A síndrome da veia
cava superior (SVCS) trata-se da obstrução ao fluxo sanguí-
Abstracts: Poster
neo na VCS. No caso em questão, o BM gerou uma SVCS por
compressão da VCS. Objetivo: Apresentar um caso clínico
em que a ocorrência de BM gerou uma SVCS, indicando a
abordagem terapêutica realizada. Caso: R.M.P, 56 anos, apresentou sintomas compressivos e edema de membros superiores e face, de moderada intensidade. A tomografia computadorizada (TC) mostrou tecido tireoidiano, diagnosticando
BM. Realizou-se ressecção através de esternotomia. No procedimento, evidenciou-se SVCS, devido à grande quantidade
de vasos venosos colaterais e compressão dos troncos venosos
braquiocefálicos direito (TVBD) e esquerdo (TVBE) pelo BM,
sendo que o último encontrava-se obstruído por fibrose de
sua parede devido à compressão prolongada, verificando-se
deficiência do fluxo no TVBE. Optou-se por colocação de
prótese de PTFE desde a região proximal do TVBE até a VCS,
corrigindo o fluxo. Houve evolução satisfatória no pós-operatório, com regressão completa e sem queixas. Discussão:
O BM é extensão de tecido tireóideo intratorácica; seu diagnóstico é clínico-radiológico para a verificação da presença
de hormônios tireoidianos, bem como TC com contraste
para a verificação de tecido tireoidianos e da circulação. Em
geral, é um quadro crônico com evolução lenta e de aspecto
insidioso, podendo ser assintomático em 65% dos casos. As
queixas mais frequentes são dispneia, tosse, edema facial e de
membros superiores (MMSS), dentre outras.
Palavras-chave: bócio mergulhante; síndrome da veia cava
superior; tireoide.
Thyroid Regulation
PO055 EL 2-IODOHEXADECANAL MODULA
NEGATIVAMENTE A NIS A TRAVÉS DE LOS PPARS
Rossich LE1; Nazar M2; Thomasz L1; Salvarredi LA1; Olgio R1;
Nicola JP2; Pisarev MA1; Masini RAM2; Juvenal GJ1 1
Comisión Nacional de Energía Atómica; 2Departamento de Bioquímica
Clínica – Facultad de Ciencias Químicas – Universidad Nacional de Córdoba Introducción: La tiroides capta iodo para que sintetice hormonas tiroideas y para que, además, cumpla un rol auto-regulatorio a través de la síntesis de lípidos iodados. De estos se
han identificado dos: la 6-iodo-lactona y el 2-iodo-hexadecanal (2-IHD). Objetivo: Determinar y comparar el efecto del
iodo y del 2-IHD y sus posibles intermediarios en la regulación de la expresión y de la actividad de NIS. Metodología
y Resultados: Se realizaron ensayos de captación de 125I
sobre células FRTL-5. Las células fueron tratadas con dosis
crecientes de KI o 2-IHD, en presencia de TSH. Se observó
que ambos disminuyen la captación del halógeno. Los datos
obtenidos fueron correlacionados con ensayos de WB para el
gen NIS. Se observó que ambos modularon negativamente la
síntesis de NIS. Se extrajo ARN total de células FRTL-5 que
fueron tratadas con dosis crecientes de KI, 2-IHD, durante
24 h, en presencia de TSH, y se realizó PCR cuantitativa. Se
observó una regulación negativa sobre la expresión de los
genes tiroideos NIS, PAX8, FOXE1, y positiva sobre la expresión de TTF-1 por parte de los dos compuestos, lo que se confirmó mediante la transfección de plásmidos que contenían
regiones promotoras de NIS, TTF-1, TTF-2 y Pax-8. Se observaron diferencias entre las construcciones de NIS, que contienen la región promotora más el potenciador vs el potenciador
solo. Análisis informáticos llevados a cabo con el programa
PROMO 3.0 permitieron identificar que la construcción del
potenciador de NIS no contiene un posible sitio de unión
de PPAR. Por tanto, se utilizaron plásmidos reporteros de
actividad de los tres PPAR conocidos (a, b y g); siendo
activados por el KI y el 2-IHD solo PPARalfa y PPARgama.
Se determinó que agonistas para ambos PPAR (fenofibrato
y rosiglitazona) mimetizan los efectos del KI y del 2-IHD
sobre los parámetros antes mencionados. Conclusión: El
2-IHD modulando la actividad de los PPARs es un posible
intermediario del iodo en el mecanismo auto-regulatorio de
la tiroides.
Palabras clave: NIS; 2-IHD; PPAR.
PO056 EFECTO ANTI-TUMORAL DE LA 6-IODO-DELTALACTONA (IL-D) EN CÉLULAS DE CÁNCER DE COLON.
Thomasz L1; Salvarredi L1; Perona M1; Oglio R1; Rossich L1;
Pisarev M2; Juvenal G3 1
CNEA; 2CNEA, UBA, Conicet.; 3CNEA, Conicet Introducción: El iodo es utilizado por la glándula tiroides
para sintetizar hormonas tiroideas y lípidos iodados. De
estos se han identificado y caracterizado dos: la IL-d y el
2-iodohexadecanal (2-IHDA) que inhiben varios parámetros tiroideos. Objetivo: estudiar el efecto de la IL-d sobre el
crecimiento tumoral. Metodología y Resultados: Las células
ARO fueron tratadas con IL-d 10 uM, TROLOX (T) y T +
IL-d durante 72 horas. La IL-d inhibió la proliferación celular
y el TROLOX revirtió el efecto. Control: 100%, IL-d 10mM:
68 %, IL-d 10mM + T: 103%, T: 90%. Al analizar la muerte
celular programada, obtuvimos un aumento en la actividad
de caspasa-3 luego de 72 h de tratamiento y el TROLOX
revirtió el efecto (p<0,05). Los ensayos in vivo se realizaron
en ratones NIH-nude, a los que se les implantó células ARO
y se les inyectó diariamente 10 mg de IL-d durante 18 días.
Observamos que el tratamiento con IL-d produjo una reducción del 30% del volumen tumoral respecto del grupo control
(p< 0,05). Al estudiar la expresión de PCNA y p27kip1, por
western blot, observamos que la IL-d produjo una inhibición
en la expresión de PCNA del 25% (p< 0,01) y un aumento del
17% en la expresión de p27kip1 (p<0,05), respecto del grupo
control. Se cuantificó la actividad de caspasa-3 y observamos que la IL-d produjo un aumento de 3,5 veces (p<0,001).
Conclusiones: la IL-d reduce el crecimiento tumoral, inhibe
la proliferación celular e induce la muerte por apoptosis.
Palabras clave: iodolípidos; cáncer; crecimiento.
Genetic
PO057 NEW CHANGES IN DUOX2 GENE IN PATIENTS
WITH DYSHORMONOGENESIS CAUSED BY IODIDE
ORGANIFICATION DEFECT
Brust ES1; Marui S1
Laboratório de Endocrinologia Celular e Molecular/Unidade de Tireoide
(LIM-25)/ Faculdade de Medicina da Universidade de São Paulo (FM/USP) 1
Iodide organification is one of the key steps in thyroid hormones synthesis. TPO plays a fundamental role, depending
on H2O2 generated by DUOX system. DUOX2 is the major
glycoprotein among DUOX, most expressed in thyroid tissue and more efficient to produce H2O2. DUOX2 mutations
cause iodide organification defect (IOD), and 21 mutations
were described causing congenital hypothyroidism (CH).
Objective: Search for mutations in DUOX2 in patients with
dyshormonogenesis caused by IOD. Methods: In previous
49
Abstracts: Poster
study, we evaluated forty patients with CH from APAE São
Caetano-Brazil. After clinical, laboratory and imaging evaluation, 7 patients had IOD. We firstly performed molecular
study of TPO and in 4 patients no mutations were identified.
All patients had eutopic thyroid, increased 131-I uptake, elevated serum thyroglobulin, positive perchlorate test and normal hearing. DUOX2 were studied in DNA from peripheral
leukocytes, including coding region and exon-intron boundaries by automatic sequence (ABIPrism 3130xl). Sequences
were compared with normal reference (OMIM 606759).
Results: Patients with CH due to IOD had 3-5 years-old at
etiological diagnosis, being 2 females. No patient reported
consanguinity and were not related. We identified 8 polymorphisms already described in 4 patients. We identified 2 new
changes in 2 patients. One patient had p.G1518S in heterozygous state and the other p.G1518S was in compound heterozygosity with p.A1087V. The remaining 2 patients showed
no changes in DUOX2. New changes were not identified in
100 control alleles. Conclusion: New mutations in DUOX2
were identified in IOD that may contribute to a better understanding of dyshormonogenesis.
Keywords: congenital hypothyroidism; DUOX2; mutation.
Iodine Deficiency
PO058 MOLECULAR CHARACTERIZATION OF THE
I- TRANSPORT DEFECT-CAUSING D287-288 NA+/ISYMPORTER MUTANT UNCOVERS RESIDUES INVOLVED IN
NA+ BINDING/TRANSLOCATION
Nicola JP1; Reyna-Neyra A1; Carrasco N1
1
Department of Cellular and Molecular Physiology/Yale School of Medicine Background: Na+/I- symporter (NIS)-mediated active accumulation of I- is a key step in the biosynthesis of thyroid hormones. Several NIS mutations have been identified as a cause
of congenital I- transport defect (ITD) and their investigation
has yielded valuable mechanistic information on NIS. A NIS
mutant lacking amino acids L287 and G288 (D287-288) was
reported to be non-functional, but was not characterized any
further. Objective: Understand the functional impairment
caused by the absence of residues 287-288, located in transmembrane segment (TMS) VIII of NIS. Methods: The activity of several TMS VIII NIS mutants was investigated using
flux assays (steady state and initial rates) and NIS expression/
localization was assessed by immunofluorescence and flowcytometry in transiently transfected Cos-7 cells. Results:
D287-288 NIS was intracellular retained in the ER; therefore,
it was not targeted to the plasma membrane and mediated no
I- transport. Furthermore, the mutant is intrinsically inactive,
as membrane vesicles from cells expressing D287-288 NIS did
not translocated I-. In addition, Ala substitution at positions
287 and 288 fully recovered NIS plasma membrane targeting and activity. Using double Ala insertions in the D287288 NIS background, we identified the region from N285 to
V293 as essential for NIS function. Ala replacements at positions N285, Q286 and L289 yielded NIS proteins with severely reduced apparent affinity for Na+. Conclusion: Residues
N285, Q286 and L289, all of which putatively face the same
side of the helix in TMS VIII, play key roles in NIS function
and seem to be involved in Na+ binding/translocation.
Keywords: congenital hypothyroidism; I- transport defect;
Na+/I- symporter (NIS).
50
Thyroid and Metabolism
PO059 LOW T3 SERUM LEVELS AND BAT IODOTHYRONINE
DEIODINASE ACTIVITY ARE ASSOCIATED WITH IMPARIED
METABOLIC FUNCTION IN A MODEL OF ANXIETY DISORDER
Mousovich-Neto F1; Landeira-Fernandes J2; Correa da Costa VM1
Instituto de Biofísica Carlos Chagas Filho/Universidade Federal do Rio de
Janeiro (IBCCF/UFRJ); 2Departamento de Psicologia/Pontifícia Universidade
Católica/Rio de Janeiro (PUC/RJ)
1
Background: Freezing in response to threat is used by many
species as an adaptive-defensive strategy. Carioca HighFreezing (CHF) rats are animals selected by their high freezing response in contextual fear conditioning and represent
a great model of anxiety disorder. Objectives: Evaluate the
impact of anxiety disorder on metabolism and endocrine
function. Methods: We evaluated oxygen consumption using
an air composition analyzer and then control male Wistar rats
(C) and CHF animals were sacrificed, serum obtained and fat
depots were removed. Corticosterone, testosterone, leptin,
thyrotropin and thyroid hormones were measured by specific radioimmunoassays. Type II iodothyronine deiodinase
activity (DIO2) was evaluated in brown adipose tissue (BAT)
by quantification of the radioiodine released by 125I-T4.
Results: Serum corticoesterone (C: 118.9±27.97 versus
CHF: 339.0±49.38 ng/mL) and leptin (C: 9,45±1.512 versus
CAC: 19,21±4.318) levels were higher in CHF animals, while
serum testosterone was decreased (C: 3.3±0.294 versus CHF:
2.0±0.29 ng/mL). Serum T3 is decreased (C: 58.40±2.401
versus CHF: 46.95±2.846 ng/dL) while T4 and thyrotropin
serum levels were unaltered in CHF animals. Fat depots weight were significantly higher in CHF animals; epididymal
(C: 2.4±0.26 versus CHF: 4.3±0.38 g) and retroperitoneal (C:
1.8±0.212 versus CHF: 3.8±0.58 g). Oxygen consumption (C:
10.55 versus CHF: 7.95 VO2 mL/min/kg 0.75) and BAT DIO2
activity (C: 0.768±0.1704 versus CHF: 0.314±0.0487 fmoles
T4.min-1.mg-1 protein) were lower in CHF than in controls
animals. Conclusions: In CHF animals, anxiety disorder
induces important endocrine and metabolic dysfunctions.
Our data clearly support an association between chronic
anxiety and endocrine and metabolic disturbances.
Keywords: thyroid hormones; anxiety disorders; endocrine
disturbances.
Hypothyroidism
PO060 EVALUATION OF HEART RATE VARIABILITY IN RATS
WITH SUBCLINIC HYPOTHYROIDISM
Apocalipse JCC1; Pilissari A1; Saviolli IH1; Duarte JS1; Sato MA1;
Giannocco G1 1
Faculdade de Medicina do ABC (FM/ABC) Background: It is not well understood if subclinical hypothyroidism (SH) can be responsible for the development of
heart disease. Objectives: To investigate the cardiovascular
autonomic modulation in rats with SH by spectral analysis.
Methods: Male Wistar rats (200-250 g, N=6/group) were submitted to surgical partial thyroidectomy (Tx) to induce SH.
The control group (CG) was submitted to the sham surgery.
We also treated the SH rats with daily i.p. injections (1X T4)
for 5 days. Afterwards, the rats were anesthetized for cannulation of the femoral artery 24 h before the experiments. The
resting systolic arterial pressure (SAP) and heart rate (HR)
were recorded for~30 min in conscious freely moving rats in a
Abstracts: Poster
PowerLab system. The HR variability in the frequency domain
(FD) and time domain (TD) were evaluated by spectral analysis using the software CardioSeries®. Data are as mean±SE and
were submitted to Student t-test (p<0.05). Results: The SAP and
HR in SH rats (117±5 mmHg and 349±14 bpm) were not different from CG (113±3 mmHg and 364±12 bpm). However, in
SH the Low Frequency (LF, 10±1 ms2/Hz) and High Frequency
(HF, 64±10 ms2/Hz) components of HR variability in the FD
were significantly higher than in the CG (LF 4±1 ms2/Hz and
HF 34±1 ms2/Hz). No difference was observed in the HR variability in the TD and in the LF component of the SAP between
SH and CG rats. Conclusions: The SH increases the sympathetic and parassympathetic modulation on the heart, without
changing resting SAP and HR.
Keywords: subclinic hypothyroidism; heart; rats.
PO061 HYPOTHYROXINEMIA DURING PREGNANCY
ALTERS NEURONAL PROJECTIONS AND THE
ESTABLISHMENT OF SYNAPSE IN THE THEIR PROGENY
Cisternas P1; Zuñiga G1; Opazo MC1; Santibañez M2; Bueno S3;
Kalergis A3; Riedel C1
1
Universidad Nacional Andrés Bello; 2Universidad San Sebastián;3Universidad
Católica de Chile
Backround: Maternal hypothyroxinemia has been considered harmless to the fetus due to only T4 be reduced. Little is
known about the effects of maternal hypothyroxinemia over
the progeny’s neuronal development. We show in this work
that maternal hypothyroxinemia is sufficient to alter the neuronal development in the progeny and the establishment of
the synapses. Objectives: To determine the impact of maternal
hypothyroxinemia on the neuronal development and the establishment of the synapse in the progeny. Material and methods:
Neuronal development and the establishment of the synapses
were studied in neuronal cultures derived from rats gestated
under hypothyroxinemia. Immunofluorescense analysis was
performed using MAP-2 and TAU total to measure the length
and number of dendrites and fillopodia. The establishment
of the synapses was analyzed by immunofluorescence using
synaptic markers as Synapsin-1 and PSD95. The contents of
Synapsin-1 and PSD-95 proteins were determined by Western
blot analysis. Long term potentiation (LTP) was assessed in vitro
by chemical LTP protocol. Results: We found that neurons derived from animals gestated under maternal hypothyroxinemia
have a short axon and small and reduced number of dendrites.
Establishment of the synapses was impaired in these neurons
and the content and translocation of synaptic proteins was also
affected. Conclusions: Our results support the findings that
maternal hypothyroxinemia during gestation could impair cognition in their progeny by affecting their neuronal development
and the establishment of the synapses.
Keywords: gestational hypothyroxinemia; neurons development; synapses establishment.
Thyroid hormone action
PO062 INFLUÊNCIA DA TEMPERATURA AMBIENTAL NO
NÍVEL DE TSH SÉRICO
Francescantonio ICM1; Rezende KN1; Borges ALF1; Castro MEC1;
Francescantonio ICCM1
1
Pontifícia Universidade Católica de Goiás (PUC/GO)
Introdução: A estimulação da via alfa-adrenérgica central
aumenta a secreção de hormônio estimulante da tireoide
(TSH) em baixas temperaturas ambientes. Objetivo:
Investigar se a temperatura ambiente tem influência na
variação sérica de TSH. Métodos: Foi realizado um estudo
transversal, com 219 pacientes, sendo 76,3% do sexo feminino, e 23,7% do masculino. Foram levantados pelo Sistema
de Meteorologia e Hidrologia do Estado de Goiás os 2 dias
mais quentes e os 2 mais frios dos anos de 2011 e 2012, para
a cidade de Goiânia.Com base nessas datas, realizou-se uma
pesquisa da dosagem de TSH de pacientes atendidos, nesse
período, em um laboratório universitário de análises clínicas,
excluindo os que possuíam dosagens fora do valor de referência para o teste (valor de referência: 0,27 a 4,2 mUI/mL). Os
dados foram tabulados em planilha do Microsoft® Excel 2007
e analisados pelo teste Manny Withney. Resultados: Não foi
observada correlação estatística entre as variáveis. No sexo feminino, a média de TSH nos dias frios foi de 3,44 mUI/mL; já
nos dias quentes, foi de 3,52 mUI/mL. No sexo masculino, as
médias foram respectivamente 2,98 mUI/mL e 3,63mUI/mL.
Conclusões: A exposição ao frio é associada a um aumento
da atividade tireoidiana; porém, ele é variável, dependendo da
duração da exposição ao frio, No entanto, observamos, assim
como Veiga et al., que as médias de TSH foram maiores para
ambos os sexos nos dias quentes, o que nos faz inferir que as
alterações nos níveis dos hormônios tireoideanos dependem
de outros aspectos relacionados à sazonalidade, e não só a
temperatura.
Palavras-chave: TSH; temperatura; variações.
PO063 REGULAÇÃO DA EXPRESSÃO HEPÁTICA DE MCT8
POR T3 DEPENDE DA INTEGRIDADE DO TRb
Almeida HN1; Pereira GF1; Império GE2; Santiago LA2;
Ortiga-Carvalho TM1
1
Janeiro (IBCCF/UFRJ); 2Universidade Federal do Rio de Janeiro (UFRJ)
Introdução: Os hormônios tireoidianos (HTs) exercem
efeitos no organismo por meio da ligação aos seus receptores nucleares (TRa1, TRb1 e TRb2). A ação dos HTs, no
entanto, depende da passagem desses através da membrana
plasmática, que ocorre por transportadores específicos. O
MCT8, membro da família dos transportadores de monocarboxilados, é fundamental no transporte de HT. Objetivo:
Avaliar o papel do TRb na regulação da expressão de MCT8
nos tecidos hepático e cardíaco de camundongos no hipo e
hipertireoidismo. Metodologia: Foram utilizados camundongos, machos, adultos, selvagens ou homozigotos (HO)
para a mutação D337T no TRb, que impede a ligação do T3 a
este receptor. O hipotireoidismo foi induzido através de PTU
(0,15%) por 5 semanas na dieta. Para a indução do hipertireoidismo, foram administradas doses crescentes de T3 (0,2;
0,5 e 1 mg/100g PC/dia s.c.) nas últimas 3 semanas. Foram
coletados fígado e ventrículo para análise do RNAm de MCT8
por RT-PCR em tempo real. Resultados: No fígado, o T3
aumentou de forma importante (259%, p<0,01) a expressão
de MCT8 em relação aos animais hipotireóideos. Já os animais HO apresentaram um aumento da expressão de MCT8
no estado do hipotireoidismo em relação aos animais normais (247%, p<0,01); entretanto, nos animais HO, o T3 não
foi capaz de aumentar a expressão do MCT8. No ventrículo,
não foi observada nenhuma alteração. Conclusão: No fígado,
51
Abstracts: Poster
T3 regula a expressão de MCT8, e essa regulação é dependente
de TRb. No ventrículo não há nenhuma regulação de MCT8,
sugerindo uma proteção deste tecido a essas variações.
Palavras-chave: MCT8; animal transgênico; TRb
PO064 AÇÕES RÁPIDAS DA TRI-IODOTIRONINA (T3) SOBRE
A EXPRESSÃO GÊNICA DA PRÓ-OPIOMELANOCORTINA
Prévide RM1; BARGI-SOUZA P1; NUNES MT1
1
Instituto de Ciências Biomédicas/Departamento de Fisiologia e Biofísica/
Universidade de São Paulo (ICB/USP) Introdução: A pro-opiomelanocortina (POMC) é um precursor do ACTH, cuja expressão se eleva no estresse, quando
também se detecta queda de TSH, T4 e T3 plasmáticos. Essas
alterações levam à especulação de que os hormônios tireoidianos (HTs) sejam integrantes de um sistema antiestresse
do organismo. Metodologia: Para avaliar essa possibilidade,
ratos Wistar foram divididos nos grupos controle (eutireóideo), tratados intravenosamente (IV) com salina ou dose
suprafisiológica de T3 (100 mg/100 g de peso corporal – PC)
e tireoidectomizado, tratados IV com salina, dose fisiológica
(0,3 mg/100 g PC) ou suprafisiológica de T3. Os animais foram
sacrificados 30 min após os tratamentos específicos; suas
hipófises foram coletadas para extração de RNA, seguindo-se
ensaio de transcrição reversa, para avaliação da expressão e
do comprimento da cauda poli(A) do mRNA da POMC, por
meio de qPCR e RACE-PAT, respectivamente. Resultados:
A tireoidectomia provocou uma queda abrupta da expressão do mRNA da POMC, a qual foi parcialmente revertida
em 30 min pelo tratamento com T3 na dose suprafisiológica.
Contudo, este tratamento, quando realizado em animais eutireóideos, levou à redução da expressão do mRNA da POMC.
Quanto à cauda poli(A), houve um aumento no seu comprimento no grupo tireoidectomizado e redução no tratado com
T3 suprafisiológico. Conclusão: O HT atua fisiologicamente,
estimulando a expressão gênica basal da POMC, e exerce
ações rápidas sobre a poliadenilação desse transcrito, conhecida etapa do controle pós-transcricional da expressão gênica.
A redução do mRNA da POMC quando ratos eutireóideos
recebem T3 suprafisiológico parece sustentar a hipótese de
que o T3 seja um hormônio antiestresse.
Palavras-chave: tri-iodotironina; tireoidectomia; pró-opiomelanocortina.
PO065 THYROID HORMONE INCREASES SEMAPHORIN
5A AND 5C GENE EXPRESSION IN RAT CORTEX AND
HIPPOCAMPUS.
Duarte JS1; Sato MA1; Giannocco G1; Souza JS2; Maciel RMB2
1
Faculdade de Medicina do ABC (FM/ABC); 2Universidade Federal de São
Paulo (UNIFESP) Background: Thyroid hormones (TH) play crucial roles in
the growth and differentiation of many organs, including the
central nervous system which contributes to the right position of neurons, axon and dendritic growth, normal layering
pattern and distribution. Two new proteins: semaphorins 5A
(SEMA5A) and 5C (SEMA5C) are involved in axon guidance
and few studies about its regulation has been made and much
less is known on its actions in the adult brain. Objective: It
becomes interesting to investigate whether TH alter SEMA5A
and SEMA5C gene expression under different thyroid status
in adult rats brain. Methods: Male Wistar rats (200-250 g)
were previously submitted to surgical thyroidectomy (Tx)
52
and subsequent treatment with methimazole (0.01%) in the
drinking water for 20 days. The control group was submitted to the same surgical procedure without the ablation of
the thyroid gland - euthyroid rats (C). Here we investigate,
by dose-response (5 X and 10 X T3, ip, 5 days), whether
T3 affects the SEMA5A and SEMA5C mRNA expressions
in cortex (Co) and hippocampus (Hip) by Real time PCR.
Results: The SEMA5A and 5C mRNA expression on 5 X and
10 X T3 exceeded the control level on Co and Hip. There is
no difference on SEMA5A gene expression between control
and Tx on Hip. The SEMA5A and 5C expression presented
a decrease on Tx when compared with control group on Co.
Conclusion: SEMA5A and SEMA5C expression, the synapses guidance proteins, are influenced by thyroid status.
Keywords: semaphorin; thyroid hormone; brain.
PO066 UP-REGULATION AMPHIREGULIN MRNA BY ACTION
INDIRECTLY OF TRIIODOTHYRONINE VIA ESTROGEN
RECEPTOR ACTIVATION
Sibio MT1; Carbonera ACL1; Oliveira M1; Olimpio RMC1; Moretto FCF1;
Luvizotto RAM1; Fecchio D1; Nogueira CR1
1
Faculdade de Medicina de Botucatu/Universidade Estadual de São Paulo
(FMB/UNESP) Several studies demonstrated the ability of the hormone triiodothyronine (T3) to increase the rate of proliferation in breast
tumor cells positive for estrogen receptor (ER). This effect was
accompanied by the induction of genes normally expressed by
the stimulation of estrogen (E2), such as amphiregulin gene
(AREG), and that this gene may be involved with inhibition
or proliferation. The objective of this study was to determine
whether T3 hormone exerts direct or indirect modulation in
AREG gene expression. To elucidate the modulation type,
MCF-7 cells were treated with T3 (10-8M) for 60 minutes
in the presence or absence of fulvestran (estrogen receptor
inhibitor – ICI) or cycloheximide (protein translation inhibitor – CHX). Gene expression was assessed by RT-qPCR,
considering statistical significance level at 5%. Treatment
with T3 increased amphiregulin 1 gene expression (±0.16,
control group) to 13.93 (±2.09, p<0.001). When treating
cells with T3 and ICI simultaneously, amphiregulin mRNA
expression decreased to 9.74 (±1.44, p<0.05) and when treating cells with T3 and CHX, amphiregulin mRNA expression
decreased to 0.88 (±0.07, p<0.001). These results demonstrate
that T3 increases amphiregulin gene expression via estrogen
receptor. The decrease in amphiregulin expression by CHX
in the group treated with T3 demonstrates that such modulation occurs indirectly, i.e., there is a need of protein synthesis prior to gene modulation. Financial support: Fundação
de Amparo à Pesquisa do Estado de São Paulo (FAPESP):
2009/15607-2.
Keywords: triiodothyronine; MCF-7; amphiregulin.
PO067 SCLEROSING MUCOEPIDERMOID CARCINOMA
WITH EOSINOPHILIA OF THE THYROID GLAND: CASE
REPORT AND REVIEW OF LITERATURE
Ferro KM1; Bueno TL1; Afonso GLP1; Guerra RA1; Portes ES1;
Oliveira OCG1; Ribas MH1; Lehn CN1 1
Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE)/SP Background: Mucoepidermoid carcinoma is usually found in
the salivary glands, breast, pancreas and digestive tract, howe-
Abstracts: Poster
ver thyroid gland involvement is uncommon. Objectives: The
aim of the study was to report a case of Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the
thyroid and review the literature. Methods: A 52-year-old
woman presented with progressive neck mass and dyspnea
since the last 7 months. She evolved with tracheal compression and underwent total thyroidectomy. Pathologically showed SMECE and lymphocytic thyroiditis and 5 of 5 positive
lymph nodes. By immunohistochemistry, cells were positive
for Cytokeratin 19 and p-67 but negative for thyroglobulin,
TTF-1 and calcitonin. Two months later, she presented with
multiple atypical lymph nodes bilaterally in levels II, III, IV
and supraclavicular fossa without involvement of the salivary gland. Measurement of thyroglobulin in fine needle
aspirates of lymph nodes was negative. Results: The patient
underwent incomplete neck dissection, including level IV
and V. Operative findings included 23 lymph nodes positive for metastasis. Postoperative chemotherapy (Cisplatin
and Adriamycin) and radiotherapy was administered. She’s
clinically stable for 8 months. Conclusions: Fewer than 40
cases have been described in the literature. SMECE is more
common in women and association with Hashimoto thyroiditis is reported. Most of these patients have a relatively indolent course, however aggressive behavior with extrathyroidal
extension or distant metastases have been noted in some
cases. This study aims to report the finding of an extremely
rare tumor of the thyroid.
Keywords: mucoepidermoid carcinoma; sclerosing mucoepidermoid; thyroid gland.
PO068 THE ROLE OF ANGIOGENESIS MARKERS IN
PHEOCHROMOCYTOMA
Ferreira CV1; Siqueira DR1; Romitti M1; Ceolin L1; Cavalcante S1;
Capp C1; Brasil BA2; Meurer L2; Maia AL1
1
Thyroid Section/Endocrine Division/Hospital de Clínicas de Porto Alegre/
Universidade Federal do Rio Grande do Sul (HC/UFRGS);2Pathology
Department, Hospital de Clínicas de Porto Alegre, Universidade Federal do
Rio Grande do Sul (HC/UFRGS)
Background: Pheochromocytoma (PHEO), a rare catecholamine producing tumor arising from the chromaffin cells,
may occurs sporadically (76%-80%) or as part of inherited
syndromes (20%-24%). The malignant form is observed in
about 14%-35% of cases. Several studies have demonstrated
that angiogenesis is a fundamental step in tumor proliferation and vascular endothelial growth factor (VEGF) seems to
be central to this process. Accordingly, VEGF inhibitors are
now widely used as anticancer agents. The role of VEGF and
its receptors in PHEO is little known. Objectives: Evaluate
the expression of VEGF-A and its receptors in PHEO and
correlate to clinical and laboratory parameters. Methods:
Twenty-two tumor specimens of PHEO (10 MEN2 and 12
sporadic, including 3 with malignant disease) were evaluated
for VEGF-A, VEGF-R1, VEGF-R2 and microvessel density
(MVD) expression by immunohistochemistry. Results: The
median age of patients with MEN2-associated PHEO was
46.5 (36.2-56.5) years and for sPHEO was 26.8 (20.7-37.3)
years. VEGF-A immunohistochemical staining was detected in 90.9%, VEGFR-1 in 45.5% and VEGFR-2 in 54.6% of
PHEO samples. No statistically significant correlation was
detected between VEGF, VEGFR-1 and VEGFR-2 expression
and age at diagnosis (p=0.87, p=0.06 and p=0.67, respectively) or tumor size (p=0.76, p=0.57 and p=0.44, respectively).
However, a significant difference was found on VEGFR-1,
VEGFR-2 and MVD expression between benign and malignant PHEO (p=0.027, p=0.029 and p=0.024, respectively)
Conclusions: These data demonstrated high expression of
the VEGF-A and its receptors in PHEO and suggest that target therapy for these factors can be considered in unresectable or metastatic tumors.
Keywords: pheocromocytoma; VEGF; microvessel density.
PO069 SORAFENIB IN THE TREATMENT OF IODINERESISTANT THYROID CARCINOMA
Danilovic DLS1; Lerario MA2; De Castro Jr G3; Camargo RYA4;
Hoff AO2
1
Unidade de Tireoide/Laboratório de Endocrinologia Celular e Molecular
(LIM/25)/Faculdade de Medicina da Universidade de São Paulo (FM/USP);
2
Serviço de Endocrinologia/Instituto do Câncer do Estado de São Paulo;
3
Serviço de Oncologia Clínica/Instituto do Câncer do Estado de São Paulo;
4
Unidade de Tireoide/Disciplina de Endocrinologia/Faculdade de Medicina
da Universidade de São Paulo (FM/USP) Background: Progressive metastatic iodine-refractory thyroid
carcinoma responds poorly to conventional chemotherapy.
Recently, phase II trials with tyrosine-kinase inhibitors, such
as sorafenib, have shown promising results in controlling
refractory disease. Objective: Describe results of sorafenib therapy in thyroid carcinomas. Methods: Retrospective
analysis of 6 patients with metastatic thyroid carcinoma (5
differentiated, 1 poorly-differentiated disease) treated with
sorafenib. Results: Six patients with progressive metastatic
disease were treated with sorafenib for 11±12 months (2-30).
Five were considered iodine-resistant after surgery and 131-I
therapy with 866±367mCi (277-1200). One patient had unressectable disease in initial evaluation. Clinical benefit, defined
as partial response (PR) and stable disease (SD), was observed in 67% of patients. One patient had SD for 7 months until
drug interruption due to hand-and-foot syndrome with unremitting pain. Durable PR was observed in 2 patients (33%)
lasting 12 and 23 months. One patient remains in PR after 3
months of treatment. Two patients did not respond to sorafenib; 1 developed intracranial hemorrhage related to skull
metastasis 2 months after starting sorafenib and the other,
with poorly-differentiated carcinoma, had evident disease
progression after 2 months of therapy. Adverse events were
observed in 83% requiring dose adjustments or discontinuation, including fatigue, lack of appetite, nausea, vomiting,
diarrhea, hand-and-foot syndrome and intracranial hemorrhage. Conclusions: Sorafenib therapy has resulted in clinical benefit in 67% of patients, similarly to published trial in
which it ranged from 70%-77%. Despite superiority of sorafenib compared to systemic chemotherapy, further development of drugs or combination of drugs with fewer side-effects
and better long-term tumor control is urgently needed.
Keywords: sorafenib; cancer; iodine resistant.
PO070 USO DE TSH RECOMBINANTE EM PACIENTE APÓS
SURTO PSIQUIÁTRICO: UMA ALTERNATIVA À PESQUISA DE
METÁSTASE NO CARCINOMA DIFERENCIADO DE TIREOIDE
Biancardi NF1; Biancardi MF1; Barcelos RN2; Pacheco CFV1
1
Centro Universitário Serra dos Órgãos (UNIFESO); 2Universidade Federal de
São Paulo (UNIFESP) A tireoidectomia total associada à ablação dos remanescentes tireoidianos com iodo radioativo é indicada em pacientes
de alto risco para implantação metastática do câncer dife-
53
Abstracts: Poster
renciado de tireoide (CDT). Para alguns casos, esse procedimento encontra-se contraindicado, sendo uma ma alternativa o uso de rhTSH. Este relato trata de paciente feminina,
terosopolitana, de 47 anos. A paciente veio ao serviço em
19/3/2008, relatando tireoidectomia total (TT) em outubro
2007, com histopatológico de carcinoma papilar variante
folicular, sendo realizado dose ablativa de radiodo seguida
à cirurgia. Submetida a rastreamento de corpo inteiro após
dose ablativa de radiodo, cintilografia de tireoide, cintilografia
óssea e telerradiografia de tórax em novembro/dezembro de
2007. Nova pesquisa de metástases em julho de 2008, através
de cintilografia óssea (CO) e pesquisa de corpo inteiro. Até
dezembro de 2009, todos os exames eram realizados mediante
suspensão prévia de levotiroxina oral com vistas à elevação
laboratorial do hormônio TSHus, confirmado laboratorialmente. Em junho de 2009, ao ser retirada a levotiroxina oral
e alcançado o hipotireoidismo clínico e laboratorial, paciente
evoluiu com surto psicótico agudo, com instabilidade emocional intensa, agressividade verbal e física, delírios persecutórios e alucinações visuais, sendo necessária intervenção
urgente da psiquiatria. Após discussão conjunta dos serviços,
levando-se em consideração que o estado de hipotireoidismo
poderia agravar ou propiciar novos surtos psiquiátricos, e,
sendo necessária a realização de novos rastreios, optou-se por
fazê-lo com rhTSH. Realizado rastreio com rhTSH em março
de 2012, não apresentando metástases, bem como CO sem
lesões osteogênicas metastáticas em esqueleto. O rhTSH tem
indicações precisas, apresentando restrições ao uso principalmente em pacientes com comorbidades prévias, sendo indicados em grupos que não toleram o hipotireoidismo, como
no caso descrito.
Palavras-chave: rhTSH; carcinoma papilar variante folicular;
surto psicótico.
PO071 SERTRALINE CAN BE USEFUL PRE-131
RADIOIODINE DOSIS IN PATIENTS WITH THYROID CANCER
MNC Silva1; Almeida MG1; Rath R2; Silva PCA3
Department of Internal Medicine/Thyroid Unit of the São José General
Hospital;2Univale University of Psichology;3Endocrine Unit/Joana de Gusmao
Childrens Hospital
1
Introduction: Sertraline is a selective inhibitor of the reuptake of serotonin, thereby increasing the neurotransmitter
5-hydroxtrytamine, inhibits beta-adrenergic receptor and
prevents depression, besides increasing the level of serum
TSH. Objectives: Analyze the efficacy of sertraline to increase serum TSH and decreasing the symptoms of depression. Methods: Twelve patients received 50 mg of sertraline
for 2 weeks before thyroid hormone withdrawn and 100 mg
of sertraline >4 weeks (Group A: 10 F/2 M; 23–67 years-old)
and compared with others 12 patients (Group B: 10 F/2 M;
28–73 years-old) that was not receiving hormone thyroid predose of radioactive iodine for the same time of 4 weeks. TSH
levels were obtained weekly in both groups. Results: In the
Group A, 3 patients had symptoms of depression without the
use of thyroid hormone, while in Group B, 7 patients showed symptoms of depression. Serum TSH level before radioiodine increased significantly more higher in the group that
received sertraline (Group A: 87±14mU/L [73-101]) compared with the control group (Group B: 69±18mU/L [51-87]
(p<0.02). Conclusions: The use of sertraline before and
during the period of thyroid hormone withdrawn can be a
54
useful method of reducing the occurrence of depression and
stimulate the increased level of TSH. References
Durval F et al.Thyroid axis activity and serotonin function in major depressive
episode. Psychoneuroendocrinology. 1999; 24: 695-712. Ronald M.Lecham. Role of thyroid hormone deiodination in the hypothalamus.Thyroid. 2005; 15: 883-897.
Keywords: sertraline; depression; hypohyroidism
PO072 IDENTIFICATION OF NOVEL VARIANTS OF RET
ONCOGENE POTENTIALLY LINKED TO THE PATHOGENESIS
OF PHEOCHROMOCYTOMA AND MEDULLARY THYROID
CARCINOMA
Bim LV1; Delcelo R2; Lima Jr JV3; Maciel RM4; Cerutti JM1
1
Genetic Bases of Thyroid Tumors Laboratory/Division of Genetics/
Department of Morphology and Genetics/Federal University of São Paulo;
2
Federal University of São Paulo/Department of Pathology; 3 Department of
Endocrinology/Santa Casa Hospital of São Paulo/;4Federal University of São
Paulo, Department of Endocrinology Background: Germline activating mutations of RET oncogene are associated with multiple endocrine neoplasia type
2 syndrome (MEN 2). Recently, our group described 2 new
variants of the RET gene in DNA isolated from the pheochromocytoma (PHEO) of a patient with MEN 2 and RET
p.G533C mutation. Objectives: Investigate whether these
new variants may represent a second hit in the genesis of
sporadic and hereditary PHEO and medullary thyroid carcinoma (MTC). Methods: A set of sporadic and hereditary
PHEO (n=24) and MTC (n=39) were selected from the files
of the Department of Pathology of the Federal University
of São Paulo, Brazil. Detection of RET variants was performed by direct sequencing of PCR products. For functional
analysis, cDNA corresponding to RET wild type (Wt) and
p.G548V and p.G533C mutations was cloned into pBudCE
4.1 plasmid and transfected into HEK 293 cells. The phosphorylation levels of p.G548V, pG533C and RET Wild type
(Wt) was evaluated by Western blot. Results: A High prevalence of p.G548V mutation was found in MTC (34.3%) and
PHEO (59%) samples. The RET p.G548V mutation increased RET Y1062 phosphorylation, compared to RET Wt. The
phosphorylation level of p.G548V and p.G533C, also located
within exon 8, were comparable. Conclusion: We report, for
the first time, the RET p.G548V variant in DNA isolated from
PHEO and MTC samples. This new variant was not found
in the matched-DNA isolated from peripheral blood. These
findings, in association with functional analysis, suggest that
this variant is related to the tumorigenesis of PHEO.
Keywords: RET; MEN 2; pheochromocytoma.
PO073 THE ROLE OF GENETIC VARIANT IN THE 3’UTR OF
THE RET PROTO-ONCOGENE ON S836S POLYMORPHISMASSOCIATED CLINICAL COURSE OF MEDULLARY THYROID
CARCINOMA
Ceolin L1; Siqueira DR1; Romitti M1; Ferreira CV1; Maia AL1
1
Universidade Federal do Rio Grande do Sul (HC/UFRGS) The RET single nucleotide polymorphisms (SNPs) have been
implicated in the pathogenesis and progression of medullary
thyroid carcinoma (MTC). Studies have shown that RET
variants could predispose or modify the natural course of
MTC. Recently, we have demonstrated an association of the
S836S variant with early onset and increased risk for metastatic disease. However, the exact mechanism as SNPs modu-
Abstracts: Poster
late the MTC pathogenesis is still open to discuss. Objective:
Here, we investigate whether the noncoding variants of the
RET gene could be associated with the L769L, S836S or
G691S/S904S SNPs. Methods: Our sample comprised 256
patients with hereditary or sporadic MTC. The RET variants
L769L, S836S, G691S/S904S and 3’UTR (rs76759170 and
rs3026785) were analyzed in DNA extracted from peripheral blood. Genotyping was performed using Custom TaqMan
Genotyping Assays. Haplotypes were constructed based on
the combination of allelic variants and their frequencies were
inferred using the phase 2.1 program. Results: The minor
allele frequencies in MTC patients were as follows: L769L:
25.3%, S836S: 5.5%, G691S/S904S: 19%, rs76759170: 5.4%
and rs3026785: 5.5%. We observed a strong linkage disequilibrium (LD) between 3’UTR variants rs76759170 and
rs3026785 (|D’|=-1, r²=1). The 3’UTR SNPs are also a strong
LD with the L769L (|D’|=-1, r²=0.16) and S836S (|D’|=-1,
r²=0.989) variants. No LD was showed among G691S/S904S
and 3’UTR SNPs. Conclusion: Our results corroborated the
hypothesis that an unknown functional variant in linkage
disequilibrium with the S836S haplotype modulates the activity of RET oncogene.
Keywords: CMT; RET polymorphisms; 3 UTR variants.
PO074 THE B-RAFV600E MUTATION IS NOT ASSOCIATED
WITH POORER CLINICAL PROGNOSIS IN PAPILLARY
THYROID CANCER
Scheffel RS1; Romitti M1; Antunes D1; Pinto Ribeiro RV1; Ceolin L1;
Dora JM1; Maia AL1
1
Universidade Federal do Rio Grande do Sul (HC/UFRGS) Background: The B-RAFV600E mutation has been associated with an increased rate of persistent disease in papillary
thyroid cancer (PTC). Therefore, it has been suggested that
the examination of B-RAFV600E mutation status could be
helpful in optimizing the management of PTC. Objectives:
Evaluate whether the B-RAFV600E mutation is associated
with persistent disease in PTC. Methods: Seventy-one unselected patients diagnosed with PTC attending the Endocrine
Division at Hospital de Cínicas de Porto Alegre, Brazil, were
included. The B-RAFV600E mutation was detected by PCR.
Persistent disease was defined as clinical or imaging evidence
of tumor and/or serum stimulated thyroglobulin >2 ng/mL.
Multiple logistic regression analysis was performed using
persistent disease as dependent variable and age, sex, TNM
stage and B-RAFV600E mutation as independent variables. Results: Of the 71 patients, 55 (77.5%) were women
and 15 (21.1%) had the B-RAFV600E mutation. The TNM
stage were as follow: 35 (49.3%) patients were in stage I, 11
(15.5%) in stage II, 9 (12.7%) in stage III and 11 (15.5%) in
stage IV. After a median follow-up of 61 months (IQR 39.591.5), 16 (22.5%) patients showed persistent disease. The
presence of the mutation was not associated with sex, age at
diagnosis or TNM stage. Regarding the prognosis, 36.4% and
26.1% of the patients with and without the mutation, respectively, have persistent disease (p=0.75). The multiple logistic
regression analysis identified age < 45 at diagnosis and TNM
stage as independent prognostic factor for persistence disease. Conclusion: The B-RAFV600E mutation was not associated with persistent disease in PTC patients.
Keywords: B-RAFV600E; papillary thyroid cancer; prognosis.
PO075 INVESTIGAÇÃO DE UM POSSÍVEL EFEITO
FUNDADOR EM FAMÍLIAS COM NEOPLASIA ENDÓCRINA
MÚLTIPLA TIPO 2 E DUPLA MUTAÇÃO P.C634Y/P.Y791F NO
GENE RET
Fonseca CCN1; Bastos AU1; Valente FOF1; Maciel RMB1; Cerutti JM1
Universidade Federal de São Paulo (UNIFESP) 1
Introdução: A neoplasia endócrina múltipla do tipo 2
(NEM2) é uma síndrome hereditária autossômica com
padrão de herança dominante e expressividade variada, classificada em 3 subtipos: NEM2A, NEM2B e carcinoma medular da tireoide familiar (CMTF); observa-se, além disso, uma
forte correlação genótipo-fenótipo. Nosso grupo identificou
5 famílias aparentemente não relacionadas com a dupla-mutação p.C634Y/p.Y791F no gene RET. Objetivo: Investigar,
utilizando marcadores polimórficos (short tandem repeats,
STR), famílias aparentemente não relacionadas e portadoras
das mutações p.C634Y/p.Y791F no gene RET, para identificar
um possível efeito fundador. Métodos: Um total de 14 indivíduos portadores da dupla mutação p.C634Y/p.Y791F no
gene RET, e 14 indivíduos sem a mutação e parentes de 1°
ou 2° grau, de 2 famílias não relacionadas, foram analisados
quanto ao padrão de repetições de 2 marcadores polimórficos
localizados no cromossomo 10 (D10S196 e D10S1652). Para
a análise, foi utilizada a técnica de reação em cadeia pela polimerase (polymerase chain reaction, PCR), seguida por análise em eletroforese capilar. O padrão de repetições foi obtido
por meio do software GeneMapper® Version 4.0 (Applied
Biosystems). O haplótipo de cada indivíduo analisado foi
construído. Resultados: O haplótipo de todos os indivíduos foi construído. Os resultados obtidos, até o presente
momento, sugerem que os marcadores D10S1652, D10S196
e as mutações p.C634Y/p.Y791F não estão em desequilíbrio
de ligação (LD). Conclusão: Os resultados preliminares não
permitem determinar se essas famílias apresentam um ancestral comum. A análise com outros indivíduos de outras famílias, aparentemente não relacionadas, está sendo realizada
para concluirmos se existe um efeito fundador para o alelo
com a mutação p.C634Y/p.Y791F.
Palavras-chave: Fonseca; Cerutti; NEM.
Thyroid Nodule
PO076 ESTABILIDAD DE LA MEDICIÓN DE CALCITONINA
INMUNO-REACTIVA EN MUESTRAS PROVENIENTES DEL
LÍQUIDO DE LAVADO DE PUNCIÓN CON AGUJA FINA
Piotrkowski-Viale F1; Dios A1; Lowenstein A1; Reyes A1; Glikman P1 1
División de Endocrinología. Hospital “J.M. Ramos Mejía” Introducción: Para diagnosticar Carcinoma Medular de
Tiroides (CMT) no siempre son concluyentes la calcitonina (CT) sérica y la citología. Nuestras mediciones preliminares de CT en líquido de lavado (LL) de punción
aspirativa con aguja fina (LLPAAF) de nódulos tiroideos,
mediante el uso de solución fisiológica (SF)–habitualmente
utilizada como LL– no replicaban en el tiempo. Objetivos:
Investigar la estabilidad de CT en diluciones de LLPAAF
durante el almacenamiento a -20ºC en: a) SF; b) otros diluyentes. Métodos: LLPAAF de 2 nódulos (N1, N2) de CMT
se lavaron con SF, midiéndose CT en los LL y en diluciones con SF(N1,N2) y diluyentes(Siemens)(N1) libres de
Tiroglobulina (TG-d), PTH (PTH-d) o CT(CT-d) inmediatamente (día 0) y en alícuotas guardadas a -20ºC (días
55
Abstracts: Poster
1y 5). Método: ensayo quimioluminiscente (IMMULITE
I, Siemens), Análisis estadístico: Tests de Friedman, Dunn,
ANOVA y Tukey-Kramer. Significativo: p<0,05. Resultados:
la CT (pg/mL) vs tiempo a -20ºC (0/1/5 días) fue: Para
N1(dil 1:50) en SF: 19,6/14,7/12,0; en TG-d: 32,0/32,9/32,0;
en PTH-d: 24,5/25,8/28,0; en CT-d: 52,0/52,0 / 53,0. N1(dil
1:150) en SF: 6,1/3,1/3,0; en Tg-d: 9,9/10,3/10,0; en PTH-d:
7,0/8,1/9,2; CT-d: 13,1/13,5/14,4. Para N2(dil 1/100) en SF:
337/239/ 205. Con el almacenamiento disminuyó la CT en
SF (p=0,0278) sin afectarse la CT en TG-d, PTH-d y CT-d.
La CT medida dependió del diluyente (p<0,0002), siendo en
CT-d mayor que en los demás (p<0,05). Conclusiones: 1.
CT en SF disminuyó con el almacenamiento a -20°C, pero
se mantuvo estable en diluyentes de PTH, CT o TG. 2.
Recomendamos: a) Medición inmediata de CT al utilizar
SF como LLPAAF para evitar falsos negativos en nódulos
sospechosos de CMT. b) Mantener el diluyente elegido para
estudios comparativos.
Palabras clave: la calcitonina, aspiración con aguja fina; carcinoma medular de tiroides.
PO077 UTILIDAD CLÍNICA DE ANTICUERPOS
ANTITIROGLOBULINA EN EL SEGUIMIENTO DEL CÁNCER
DIFERENCIADO DE TIROIDES. ESTUDIO RETROSPECTIVO
Millar ES1; Utreras C1; Díaz RE1; Véliz J1; Wohllk N2 1
Sección de Endocrinología, Hospital del Salvador, Universidad de Chile;
2
Sección de Endocrinología, Hospital del Salvador, Universidad de Chile,
IEMA Introducción: La tiroglobulina sérica (Tg) es el marcador en el seguimiento del cáncer diferenciado de tiroides
(CPT); la presencia de anticuerpos tiroglobulina (AcTg)
pueden interferir en su medición, dificultando la monitorización de la enfermedad. La persistencia de AcTg se
ha relacionado a un aumento del riesgo de recurrencia.
Objetivos: Evaluar el comportamiento y significado de los
AcTg durante el seguimiento de CPT en pacientes con y
sin recurrencia de enfermedad; determinar si la presencia de tiroiditis crónica (TC) afecta la evolución de los
AcTg. Pacientes y métodos: Se estudiaron 146 pacientes
con CPT sometidos a TT y I-131, entre 2003 y 2011. Se
excluyeron variantes histológicas agresivas y metástasis
a distancia. Seguimiento 12 meses-8 años (promedio 36
meses). Cuarenta y un pacientes presentaron AcTg, inicialmente o durante el seguimiento: 28 con TC y 13 sin TC
(STC). La determinación de AcTg se realizó por quimioluminiscencia (Immulite 2000). Se realizó un análisis estadístico mediante el programa STATA. Resultados: 8/28
pacientes con TC (28%) y 5/13 STC (38%) presentaron
recurrencia. (p=ns). Los AcTg, en los pacientes que recidivan, presentan valores más elevados (p=0,002) y persisten
en el tiempo (p=ns), especialmente en el grupo STC. Los
AcTg, en los pacientes libres de enfermedad, desaparecen
a los 18 meses. Conclusiones: La persistencia de AcTg a
títulos elevados podría ser un marcador indirecto de recidiva tumoral. Aunque no hubo diferencia significativa,
la recurrencia fue mayor en el grupo STC, lo que podría
explicarse por el bajo número de pacientes.
Palabras clave: cáncer papilar de tiroides, anticuerpos de
tiroglobulina, tiroiditis crónica.
56
PO078 ANOMALOUS THYROGLOBULIN – A NEW PUZZLE
FOR A WELL KNOWN PROTEIN?
Xavier ACW1; Kasamatsu TS1; Oliveira KC1; Harada MY1; Mendes
A2; Meneghetti MCZ2; Lima MA2; Kunii IS1; Furuzawa GK1; Ikejiri E1;
Mamone MCC1; Maciel RMB1; Vieira JGH1; Dias da Silva MR1;
Martins JRM3; 1
Laboratory of Molecular and Translational Endocrinology/Escola Paulista
de Medicina/Universidade Federal de São Paulo (EPM/UNIFESP); 2Division
of Molecular Biology/Escola Paulista de Medicina/Universidade Federal de
São Paulo (EPM/UNIFESP); 3Laboratory of Molecular and Translational
Endocrinology and Division of Molecular Biology/Escola Paulista de
Medicina/Universidade Federal de São Paulo (EPM/UNIFESP) Introduction: Measurement of thyroglobulin (TG) is a cornerstone in the follow-up of patients with differentiated thyroid
carcinoma (DTC). A main limitation in its use is the presence
of endogenous TG antibodies that can lead to falsely low
results. Posttranslational modifications of TG structure during
carcinogenesis have been implicated with this more TG immunogenic profile. Objective:Investigate a possible structural
difference on TG that could distinguish between benign from
malignant lesions. Methods: Tissues from normal and tumoral
tissues were obtained from patients who underwent thyroidectomy. TG was purified and analyzed by gel filtration on high
performance liquid chromatography-HPLC. Eluted fractions
were numbered and assayed for TG using an in-house immunoassay. Afterwards, fractions were subjected to SDS-PAGE
gel electrophoresis and TGs identified by immunoblotting
with mono and polyclonal anti-TG antibodies. Additionally,
washout of fine-needle aspiration of thyroid nodules (n=48)
was obtained and analyzed by the same methodology. Results:
HLPC profile showed a higher amount of peak 16 from tumoral if compared to normal tissue. Immunometric TG was
detected only in the peak 13 for normal and tumoral tissue.
However, polyclonal antibody react with the peaks 13 and 16
whilst monoclonal immunoblotting lacks its recognition for
peaks 16. Interestingly, similar results were obtained for the
fine-needle aspiration samples. Conclusion: This study revealed a distinct population of TG that is differentially expressed according to the kind of antibody employed for analysis.
Further studies will be necessary, but if confirmed, this finding
seems to be promising especially for development of specific
assays for tumoral TG.
Keywords: anomalous thyroglobulin; thyroid cancer; diagnosis.
PO079 RELATION BETWEEN POSTOPERATIVE STIMULATED
THYROGLOBULIN AND FOLLOW-UP WITH SERUM
THYROGLOBULIN FOR THYROID CARCINOMA
Lira RB1; Chulam TC1; De Carvalho AY1; De Carvalho GB1; Kowalski LP1
1
Department of Head and Neck Surgery and Otorhinolaryngology/Hospital
AC Camargo
Background: Serum thyroglobulin is one of the main tools
of follow-up after total thyroidectomy for well-differentiated
thyroid carcinoma, and the closer to 0 is the value at baseline, more sensitive in detecting recurrences is the method.
Objectives: To assess the relations between value of postoperative stimulated thyroglobulin and serum thyroglobulin in early
follow-up in patients who underwent total thyroidectomy for
well differentiated thyroid carcinoma. Methods: Retrospective
analysis of 292 cases of thyroid cancer surgery between 2008
and 2010 without pathological risk factors (extrathyroidal
extension and lymph node metastasis), without the presence of
detectable anti-thyroid anti-bodies, in which information rela-
Abstracts: Poster
ting to radioiodine therapy, postoperative stimulated thyroglobulin and serum thyroglobulin after 6 months of surgery were
available. Results: All 89 patients with stimulated TG<1 ng/
mL had TG<1 ng/mL at 6 months follow-up, whereas in the
group stimulated with TG>1 ng/mL, 14 (6.9%) of patients had
TG>1 ng/mL this dose at 6 months (p=0.005). The postoperative radioiodine showed no impact on this relationship: the
group without radioiodine therapy, 69 (94.5%) patients had TG
<1ng/mL, and in the group that received ablative dose of 131-I,
209 (95.4%) of patients had TG<1 ng/mL 6 months after surgery. Conclusions: In this sample, stimulated thyroglobulin in
the early postoperative of total thyroidectomy (approximately
30 days) showed a strong determining relation to the value of
serum thyroglobulin in the first follow-up appointments, which
reinforces the importance, for this purpose, of a adequate surgery to result in a stimulated thyroglobulin under 1 ng/mL.
Keywords: thyroid carcinoma; thyroglobulin; follow-up.
PO080 IS POSTOPERATIVE RADIOIODINE THERAPY
HELPFUL IN FOLLOW-UP USING SERUM THYROGLOBULIN?
Lira RB1; De Carvalho AY1; Vartanian JG1; Filho JG1; Kowalski LP1
Department of Head and Neck Surgery and Otorhinolaryngology/
Hospital AC Camargo 1
Background: One of the arguments that suggest benefit in
the use of ablative dose of 131-I after thyroidectomy for welldifferentiated thyroid carcinoma in all patients is that this
practice helps in postoperative follow-up with serum thyroglobulin, making it more uniform. Objectives: To analyze the
impact of postoperative radioiodine in thyroglobulin values
during the early follow-up of patients who underwent total
thyroidectomy for papillary thyroid carcinoma. Methods:
Retrospective analysis of 412 cases of thyroid cancer treated between 2008 and 2010 in which information relating
to radioiodine therapy, postoperative stimulated thyroglobulin and thyroglobulin at 6 months after surgery were available. Results: Analyzing the values of serum thyroglobulin
measured 6 months after total thyroidectomy in patients who
did not receive postoperative radioiodine therapy, 82 (93.2%)
had TG values <1 ng/mL, whereas in the group that received
radioiodine, 303 (93.5%) had TG<1 ng/mL. Excluding cases
with pathological factors of increased risk (which would be
indicated for adjuvant radioiodine) and cases with positive
anti-thyroglobulin, we observed equivalent numbers. In the
group without radioiodine therapy, 69 (94.5%) patients had
TG<1 ng/mL, and the group that received ablative dose of
I131, 209 (95.4%) patients had TG<1 ng/mL after 6 months of
surgery. Conclusions: The use of postoperative radioiodine
aiming adjuvant ablative of thyroid remains had no impact on
levels of serum thyroglobulin in the follow-up 6 months after
total thyroidectomy. Therefore, the argument that the use
of postoperative ablative dose of 131-I makes the follow-up
easier is questionable.
Keywords: serum thyroglobulin; thyroid carcinoma; postoperative radioiodine therapy.
PO081 CARACTERIZAÇÃO DE CURVA ANALÍTICA PARA
DETERMINAÇÃO DO IODO NO LEITE MATERNO
Catarino RM1; Martini F1; Peres NS1; Ferreira JE1; Maeda MYS1;
Santos RTM1 1
Instituto Adolfo Lutz O monitoramento da concentração do iodo no leite materno
é clinicamente importante, considerando-se as patologias
relacionadas à deficiência ou excesso de iodo às mães e aos
recém-nascidos. Objetivo: Determinar curva analítica para
a detecção de iodo no leite materno utilizando amostras de
leite não humano e água ultrapura previamente estabelecidos. Materiais e métodos: Foram utilizadas amostras de leite
não humano e água ultrapura suplementados com iodeto
de potássio nas concentrações de 0; 2; 5; 10 e 15 mg/dL e 5
amostras de leite materno. Após tratamento do leite materno
e não humano para eliminação de possíveis interferentes,
foram obtidas 2 fases: sólida (camada de gordura) e líquida.
Na fase líquida, foi utilizada a metodologia baseada na reação
bioquímica e colorimétrica de Sandell-Kolthoff (1937), recomendada pela Organização Mundial da Saúde (OMS). Para
comparar as curvas analíticas, A (leite não humano) e B (água
ultrapura), utilizamos o coeficiente de correlação (R2). Para
avaliar a seletividade das curvas foram analisadas a média
(M) e o desvio padrão (DP) das amostras de leite materno.
Resultados: Foram obtidos os coeficientes de correlação
nas curvas analíticas de leite não humano (r=0,99) e água
ultrapura (r=0,97). Os resultados da comparação das curvas
analíticas com amostras de leite materno foram: A (143,40
mg/L/2,65) e B (143,20 mg/L/2,59) (média + DP). Conclusão:
A metodologia para a seletividade das curvas analíticas em
amostras de leite não humano e água ultrapura demonstrou
ser reprodutível, pois observamos que podem ser utilizadas
ambas as curvas para a finalidade pretendida, aplicadas em
estudos clínicos para as dosagens de iodo no leite materno.
Palavras-chave: iodo no leite materno; leite não humano;
seletividade de curvas analíticas.
PO082 VALIDADE DA REPETIÇÃO DA PUNÇÃO BIÓPSIA
ASPIRATIVA PARA NÓDULOS DE TIREOIDE
Graciano AJ1; Ferreira SJ1; Fischer CA1; Peixoto AJA1; Bublitz GS2
1
Hospital São José; 2CEDAP Introdução: Atualmente a punção aspirativa com agulha fina
(PAAF) baseada no sistema de relatório Bethesda apresenta
6 categorias citopatológicas para nódulos de tireoide, com
recomendações de conduta para cada categoria. A repetição
da PAAF é sugerida para punções iniciais não diagnósticas
e lesões foliculares indeterminadas. Todavia, a repetição da
punção nos casos com citopatológico inicial benigno é controversa. Portanto, mais estudos são necessários para se avaliar as indicações e a validade de punções repetidas de nódulos tireoidianos. Objetivo: Avaliar os resultados de pacientes
submetidos a punções repetidas de tireoide, determinando
a sua validade para a conduta terapêutica. Metodologia:
Estudo retrospectivo incluindo 422 pacientes com nódulos
de tireoide submetidos a punções repetidas em período de
3 anos de seguimento. Resultados: A punção repetida foi
indicada para 237 casos Bethesda 1 (56,16%); 152 Bethesda 2
(36,01%); 23 Bethesda 3 (5,45%) e 10 Bethesda 4 (2,36%). A
punção repetida após PAAF não diagnóstica colocou 70,5%
desses casos em outra categoria, sendo 5% destes considerados sugestivos para malignidade. Observou-se que dos 56,53%
dos casos com PAAF inicial Bethesda, 3 foram colocados em
outras categorias diagnósticas na segunda punção, e 4,35%
destes foram considerados suspeitos para malignidade. Para
57
Abstracts: Poster
pacientes com PAAF inicial benigna, foi confirmando resultado de benignidade em 71,05% das PAAFs repetidas, mas
3,28% destas passaram para maligno ou suspeito. Conclusão:
A PAAF repetida pode resultar em informações válidas para
pacientes com punção inicial não diagnóstica e naqueles com
lesões foliculares indeterminadas. Sua aplicação em casos
benignos parece pouco eficaz.
Palavras-chave: thyroid; câncer; citologia.
PO083 PAAF DE NÓDULOS TIROIDEOS GUIADA POR
ECOTOMOGRAFÍA. VALOR DEL TIRADS
Jiménez M1; Sapunar J1; Granzotto C1; Roa JC1; Gayoso R1; Huenchullan C1 1
Clínica Alemana Temuco Introducción: El bocio nodular es frecuente. Se han realizado esfuerzos para aunar criterios US y definir cuáles son
de riesgo y requieren PAAF. TIRADS reúne criterios ecográficos. Objetivo: Evaluar el valor de TIRADS en predecir
nódulos sospechosos en la región de la Araucanía. Material
y método: Se ingresaron PAAF realizadas en la Clínica
Alemana Temuco, entre junio de 2007 y agosto de 2012. Se
registraron datos clínicos como: edad, sexo, patología tiroidea asociada y características US. Luego se clasificaron según
TIRADS y se envió a estudio citológico (extendido y block
celular), informada según clasificación británica. Resultados:
892 PAAF, promedio de edad 47,7 ± 14,4 años, distribución
por sexo 91,5% mujeres. El resultado de las citologías fue de
47,9% y 12,7% negativa y positiva para células neoplásicas,
respectivamente. 16.9% frotis atípico, 3.6% lesión folicular
y 16,9% no diagnóstica. Este último porcentaje fue excluido
del análisis. El tamaño promedio: 23,1 ± 10,2 mm, el 32%
micronódulos, 6,6% nódulos ≥ 40mm e intermedio 61,4%.
No hubo diferencias significativas en la probabilidad de citología positiva entre los diferentes tamaños. Distribución de
citología según TIRADS. TIRADS Citología neg Citología pos p 2 11(90,9%) 1(9,1%) 0,08 3 145(69,2%) 67(30,8%) 0,09 4a 209(61,4%) 134(38,6%) 0,0 4b 48(42,6%) 64(57,4%) 0,007 5 2(11,1%) 13(88,9%) 0,02 La clasificación TIRADS resultó adecuada en predecir los
nódulos de mayor riesgo de tener citología positiva. A mayor
categoría TIRADS incrementa probabilidad de citología sospechosa de malignidad. TIRADS tiene valor para predecir el
riesgo de una citología positiva en esta población.
Palabras clave: bocio nodular; TIRADS; ecografía.
Thyroid Cancer Basic
PO084 INCREASE OF METALLOPROTEINASES (MMPS)
ACTIVITY AND MIGRATORY ABILITY OF THYROID
TUMOR CELLS INDUCED BY TUMOR CELL-FIBROBLAST
INTERACTION
Della Vedova AB1; Remedi MM1; Gilardoni MB1; Masini-Repiso AM1;
Pellizas CG1; Donadio AC1 1
Facultad de Ciencias Químicas/Universidad Nacional de Córdoba (CIBICI/
CONICET) Background: Carcinomas comprise tumor and stromal cells
like fibroblasts (Fb), immune and endothelial cells immersed
in the extracellular matrix (ECM).Tumor-stroma cross-talk
influences tumor behavior. Proteases like MMPs induce ECM
58
degradation and epithelial-mesenchymal transition. Fb confers growth-promoting advantage to thyroid carcinoma cells.
The role of thyroid tumor-Fb interaction in the invasive and
migratory ability of tumor cells remains unknown. Objectives:
To analyze MMPs expression and thyroid tumor cell migration induced by tumor-Fb interaction. Methods: Thyroid
carcinoma papillary (TPC-1), anaplastic (8505c) and normal thyroid (N-ThyOri) cell lines were cultured with (cocultured) or without normal Fb. MMP2-MMP9 expression
was analyzed in culture supernatants (Conditioned-Media,
CMs) by zymography and in cultured cells by immunofluorescence. Tumor cell migration was evaluated by the wound
healing assay and the presence of lamellipodia/filopodia, as
a signal of migratory phenotype (rhodamine-phalloidin staining). Results: An increase in MMP2 and MMP9 expression
alongside with higher levels of active MMP2 was observed
in CMs from TPC-1-Fb and 8505c-Fb co-cultures. MMP9
protein staining increased in Fb co-cultured with tumor
cells while MMP2 displayed a dotted pattern in Fb plasmatic membrane. No significant MMPs changes were observed in N-ThyOri-Fb co-cultures. TPC-1 and 8505c cells
with lamellipodia/filopodia increased after Fb CMs as well
as 8505c cells after tumor-Fb CMs incubation. A significant
wound healing closure was observed only in 8505c cells, after
incubation with Fb or 8505c-Fb CMs. Conclusions: Tumor
cell-Fb interaction increased MMP2 and MMP9 expression
and activity. Fb soluble factors could be relevant for the promotion of thyroid tumor cell invasive phenotypes.
Keywords:thyroid tumor; fibroblast; metalloproteinases.
Thyroid Nodule
PO085 USO DEL SISTEMA BETHESDA EN CITOLOGÍAS DE
ALTO RIESGO DE PUNCIONES BIOPSIAS TIROIDEAS.
Gutnisky L1; Delfino L1; Laudi R1; Deira S1; Rivadeneira S1; Santander
M1; Olstein G1; Reyes A1; Lowenstein A1
1
Hospital Ramos Mejía
Introducción: Clasificamos las Citologías tiroideas de Alto
riesgo de malignidad en 4 categorías: Proliferaciones foliculares de bajo grado (PFBG), alto grado (PFAG), de células de Hürthle (PCH) y sospechosas de malignidad (SM).
Desde 2011 utilizamos el Sistema Bethesda (SB). Objetivos: A)
Reclasificar las citologías de alto riesgo según SB. B) Evaluar
si el SB diferencia prevalencia de malignidad. C) Establecer
evolución de la Categoría (C). Materiales y Métodos: Fueron
estudiados 81 casos en forma retrospectiva y prospectiva.
Se revisaron los informes y/o preparados de alto riesgo y se
categorizaron por el SB. Se correlacionó con cirugía o evolución. Se calcularon las diferencias en malignidad en las C
por Chi2. Resultados: Todas las PFBG se clasificaron como
C3 (24/24), las PFAG, como C4 (21/23) y C5 (2/23); las PCH,
como C4 (13/14) y C5 (1/14) y las SM, como C4 (1/20) y C5
(19/20). La prevalencia de malignidad en C3 (n: 24), C4 (n:
35) y C5 (n: 22) fue de 4,3%, 48,6% y 90%, respectivamente
(p< 0,01). De la C3, 6/24 pacientes fueron a cirugía por clínica, todos con histología benigna. Los casos repunzados
fueron C2, 9/18; permanecieron en C3 4/18; C4, 3/18 y C5,
2/18 [1 carcinoma papilar (CP)]. Conclusiones: 1) La utilización del SB ubicó sin dificultad las Citologías de Alto Riesgo.
2) Las diferencias significativas en las malignidades en cada
categoría avala el uso del SB. 3) La repunción en C3 permitió
Abstracts: Poster
indicar cirugía (5/24) e identificar 1 CP, y se afirma como un
paso fundamental en el seguimiento.
Palabras clave: sistema bethesda; citología tiroidea; alto
riesgo.
PO086 ANÁLISE CITO-HISTOPATOLÓGICA DOS NÓDULOS
TIREOIDIANOS SUSPEITOS (BETHESDA IV/V)
Silva MC1; Pereira CG1; Colombo BS1; Ronsoni MF1; Hohl A1; Vieira
DSC1; Canalli MHBS1
1
Hospital Universitário/Universidade Federal de Santa Catarina (HU/
UFSC) Introdução: Punção aspirativa por agulha fina (PAAF) é
considerada padrão-ouro na avaliação de lesões tireoidianas.
Nódulos tireoidianos (NTs) com citopatologias (CPs) suspeitas para neoplasia folicular ou para malignidade continuam
como desafio para decisão terapêutica. Objetivo: Avaliar a
experiência no citodiagnóstico de NTs suspeitos para neoplasia folicular ou para malignidade no HU/UFSC. Métodos:
Estudo transversal, de 2000 a 2012, com análise cito-histopatológica (CHP) dos NTs de pacientes tireoidectomizados por
citodiagnósticos de Bethesda IV (B4 – neoplasias foliculares)
e Bethesda V (B5 – suspeitas para malignidade). Laudos CP
anteriores a 2010 foram reclassificados conforme o sistema
Bethesda. Resultados: Foram estudados 80 pacientes, idade
média de 48 anos e predominância do sexo feminino (90%).
À ultrassonografia de tireoide, 70% dos NT apresentaram de 1
cm a 3 cm no maior diâmetro. Em relação à CP, 55 indivíduos
(68,7%) foram classificados como B4 (78% neoplasia folicular e 22% lesão oxifílica) e 25 (31,3%) como B5. Malignidade
foi confirmada em 50% da totalidade dos casos. Nos B4, 40%
foram carcinomas (17 papilíferos, 2 foliculares e 3 de células
de Hürthle). Nos B5, 72% confirmaram malignidade (17 carcinomas papilíferos e 1 carcinoma folicular). Conclusão: A
análise dos resultados CHP dos pacientes submetidos à tireoidectomia total em nosso serviço demonstrou maior taxa de
positividade para malignidade para os nódulos B4 (40%) em
comparação com os dados descritos pelo sistema Bethesda
(15%-30%). Já os nódulos B5 (72%), mostraram taxa semelhante aos dados da literatura (60%-75%).
Palavras-chave: tireoide; nódulos; citopatologia.
PO087 CLINICAL AND PATHOLOGIC FEATURES OF
SPORADIC AND FAMILIAR PAPILLARY THYROID
CARCINOMA IN CHILDREN, ADOLESCENTS AND YOUNG
ADULTS
Medeiros MFS1; Pereira DP1; Strappa GBS1; Souza M1; Lima CRA2;
Fonseca Jr LE3; Silva IC4; Lobão LJ5; Ramos HE1
1
Departamento de Biorregulação/Instituto de Ciências da Saúde/Universidade
Federal da Bahia (ICS/UFBA); 2Serviço de Cirurgia de Cabeça e Pescoço/
Hospital São Rafael (HSR); 3Departamento de Anatomia patológica e
Medicina legal/Faculdade de Medicina/Universidade Federal da Bahia (FM/
UFBA); 4Serviço de Anatomia Patológica/Hospital São Rafael (HSR); 5Serviço
de Medicina Nuclear/Hospital São Rafael (HSR) Background: Thyroid cancer is rare in childhood, adolescence and young adults (0.5%-1.5% of all malignancies).
However, the incidence in this group is rising. The most
common type for this age group is the differentiated thyroid
cancer (DTC). Objectives: Establish the essential features of
sporadic and familiar papillary thyroid carcinoma (PTC) in
children, adolescents and young adults, and the relationship
of tumor pathology to extrathyroidal extension (ETE), lymph
node, distant metastasis and positivity for BRAFV600E mutation. Methods: Retrospective study with assessment of clinical and histological features of 36 cases of DTC in patients of
0-21 years-old registered during 2000-2012 years. DNA was
extracted from paraffin-embedded tissue and applied for PCR
and sequencing. Results: Female/Male ratio was 3:1. Mean
age: 16 years-old; 30% were patients <15 years-old. Familiar/
Sporadic cases were 1:4.The histological PTC subtype:
Classical (26/36), Follicular (9/36) and Solid Variant (1/36).
Mean tumor size was 36 mm. 53% had multifocal growth and
regional lymph node metastasis. ETE and distant metastasis were established in 6/36 and 4/36 patients, respectively.
Conclusion: BRAFV600E mutation is still under analysis.
A high frequency of ETE and lymph node metastasis were
detected. The strongest factor associated with both of them
was tumor size.
Keywords: childhood; thyroid cancer; BRAFV600E.
PO088 CARCINOMA PAPILAR TIROIDEO. RECIDIVA TARDÍA
CON METÁSTASIS MÚLTIPLES
Sepúlveda A1; Eugenin D2 1
Clínica Santa María; 2Universidad de los Andes Hombre de 62 años. Antecedentes: cáncer papilar tiroideo
operado en 1992 (nódulo de 2 centímetros, papilar clásico,
sin metástasis ni invasión capsular).Recibe 100 milicuries de
radioyodo y evoluciona con tiroglobulinas indetectables,TSH
suprimida (levotiroxina 150 ug). Dado de alta en 2006.
Presenta fibrilación auricular. Usuario de amiodarona. Se
presenta a una consulta en 2011 por dolor lumbar y cadera
derecha. Resonancia Magnética Nuclear: lesiones líticas
T8-T11.TAC y PET: masa suprarrenal izquierda, múltiples lesiones pulmonares bilaterales, masa costal izquierda,
metástasis hepáticas cadera derecha. La biopsia de laminectomía T11 confirma la metástasis de carcinoma papilar bien
diferenciado. Se realiza fijación T9-T11, suprarrenalectomía
izquierda y radioterapia de columna. Posteriormente, neumonectomía izquierda, osteosíntesis de cadera y radioterapia.
Luego de 3 meses de suspensión de amiodarona, a pesar de
yoduria elevada (2000), recibe 300 milicuries de radioyodo
(TSH:58, TG: 7220). La búsqueda sistémica confirma captación en todos los sitios. Recibe una segunda dosis de 300 milicuries al cabo de 6 meses. TG actual: 252 ng/dL. Discusión:
El cáncer papilar de tiroides presenta diseminación solo en
2%-10% de los diagnósticos y las metástasis tardías se asocian
con factores de mal pronóstico (hombre mayor de 45 años,
>2 centímetros, variante histológica, invasión capsular) que
este paciente no tenía. Creemos que el seguimiento debe ser
de por vida y que se debe evitar el uso de amiodarona en estos
pacientes. Por otro lado, la acumulación de dosis total de 700
milicuries (riesgo hematológico: leucemias, pancitopenia,
cánceres secundarios) plantea el uso de inhibidores de la tirosin kinasa.
Palabras clave: Cáncer papilar tiroideo; Metástasis; amiodarona.
PO089 NÓDULO PARASÍTICO DE TIREOIDE ASSOCIADO A
BÓCIO MULTINODULAR ATÓXICO
Hospital Estadual Américo Brasiliense (HEAB) 1
Introdução: A presença de tecido tireoidiano localizado na
face lateral do pescoço sem nenhuma inclusão em linfonodos
59
Abstracts: Poster
é uma entidade extremamente rara, não tendo relação com o
desenvolvimento da tireoide e sendo de difícil diferenciação
da metástase do carcinoma de tireoide. Objetivo: Apresentar
o caso de um paciente portador de tireoide com dimensões
aumentadas associada a 2 nódulos heterogêneos em topografia submandibular esquerda, de natureza sólida, que, apesar
de serem sugestivos de metástase de carcinoma diferenciado
de tireoide, tratava-se de 2 nódulos parasíticos de tireoide.
Métodos: Paciente do sexo masculino, 40 anos, apresentava
um bócio tireoidiano aumentado de volume às custas de
nódulos bilaterais de 3,7 cm e 3,3 cm e função tireoidiana
normal. A punção com agulha fina confirmou a benignidade
da glândula e a etiologia tireoidiana dos 2 nódulos submandibulares em nível II do pescoço à esquerda. Resultados: Em
virtude da confirmação de tecido tireoidiano ectópico em
região lateral do pescoço sugestivo de metástases, o paciente
foi submetido à tireoidectomia total + esvaziamento cervical
radical modificado com preservação do nível I. Foi confirmado diagnóstico de bócio multinodular associado a 2 nódulos parasíticos de tireoide através de estudo imuno-histoquímico. Conclusões: O nódulo parasítico de tireoide é uma
entidade pouco conhecida por cirurgiões e patologistas. O
diagnóstico requer que o tecido esteja no mesmo plano facial
da tireoide, não esteja associado com linfonodos e mostre
um aspecto histológico similar ao da glândula tireoide. Seu
conhecimento é de grande importância na definição de condutas e evitar cirurgias desnecessárias.
Palavras-chave: nódulo parasítico; tireoide; bócio multinodular.
PO090 CONTRIBUTION OF THE BIOLOGICAL DOSIMETRY
FOR TREATMENT DECISIONS IN PATIENTS WITH
DIFFERENTIATED THYROID CARCINOMA (DTC) UNDER
RADIOIODINE-131 THERAPY
Chebel GM1; Di Giorgio M2; Radl A2; Taja MR2; Bubniak R2; Deminge
M2; Oneto A3; Fadel AM1
1
Endocrinology Division/Dr. Carlos Durand Hospital; 2Biological Dosimetry
Laboratory/Nuclear Regulatory Authority; 3TCba/Salguero Laboratory
Radioiodine-131 therapy is applied in patients with DTC, following
thyroidectomy for the ablation of thyroid remnants and treatment of
metastatic disease. Objective: Estimate the absorbed dose to the whole body and
bone marrow, due to the therapeutic administration of 131-I
in patients with DTC, by applying cytogenetic techniques for
treatment decisions. Patients: Thirty-three DTC patients with
total thyroidectomy, followed by 131-I therapy, with cumulative activities from medium to high (exceeding 37.0 GBq) and
persistent/recurrent disease, were assessed. Methods: A prospective clinical follow-up was conducted, and was correlated
with cytogenetic, haematological and endocrinology data. For
the cytogenetic studies, blood samples were obtained before
each patient treatment and on day 8 after the administration of
131-I. Cytogenetic methods were applied to quantify chromosome aberrations for dose assessment. Results: This work show
that the biological dosimetry have contributed to optimize the
131-I therapeutic administration in 5 out of the 33 patients
evaluated with cumulative activities higher than 1000 mCi
and to decide the application of a complementary surgery in
1 case. For the remainder, the routine treatment protocol was
applied as the biodosimetry confirmed that this further 131-I
administration would result in a low risk of reaching the myelotoxicity threshold (2Gy). Conclusion: From a clinical point
60
of view, the biodosimetry conducted on samples from patients
with previous treatments, before a new therapeutic administration could allow the cytogenetic status assessment (radiation
damage and repair capacity) to become a warning signal for
reducing potential hematological complications.
Keywords: differentiated thyroid carcinoma; biological dosimetry; hematological complications.
PO091 ANALYSIS OF MOLECULAR PROFILE OF PEDIATRIC
THYROID CANCER
Cordioli MICV1; Moraes LS1; Besson PS1; Delcelo R1; Alves MTS1;
Monte O2; Longui CA2; Cury AN2; Cerutti JM1
1
Universidade Federal de São Paulo (UNIFESP);2Irmandade da Santa Casa de
Misericórdia de São Paulo (SCMSP) Background: Thyroid cancer represents only 0.5%-1.5% of
all pediatric malignancies, but the incidence appears to be
increasing. Comparing to adult patients, there is little information about clinical, histological and molecular profile what
prompts the development of this study. Objectives: Correlate
clinical-pathological features with molecular profile in pediatric thyroid cancer. Methods: Patients up to the age of 18
years (n=49), submitted to thyroid surgery, were included in
this study. Results: A total of 34 patients with differentiated
thyroid cancer (DTC) and 15 patients with benign thyroid
lesions were considered. The occurrence of BRAF V600E
mutation was detected in 6 (17.64%) patients. In these patients,
the tumors size was significantly larger (p=0.0174). The expression of thyroglobulin has showed lower values in malignant
tumors (p=0.0112), specially in patients with BRAF V600E
mutation(p=0.0062), and it was associated to an increase in
cervical metastasis rates(p=0.0095). The expression of NIS and
TSH-R did not show a significant difference between benign
and malignant tumors. Conclusions: The clinical features of
DTC are markedly different in pediatric population, and this
fact may probably be associated with different molecular profile in this group. The BRAF V600E mutation, the most prevalent in adults, showed a low rate in the pediatric group. The
difference in iodine metabolism genes expression between
pediatrics and adult patients may explain some of the differences verified in clinical features, evolution and prognosis according to age. The understanding of molecular profile of DTC in
the pediatric group may be useful for future developments of
therapeutic approaches for this group of patients.
Keywords: thyroid cancer; pediatric; molecular profile.
PO092 ANÁLISIS DE MUTACIÓN DEL ONCOGEN BRAF EN
POBLACIÓN ARGENTINA
Ilera V1; Dourisboure R1; Colobraro A1; Silva Croome MC1; Olstein G1;
Zunino A1; Lowenstein A1; Reyes A1; Gauna A1 1
Hospital Ramos Mejía Introducción: La mutación del oncogen BRAF en carcinoma
papilar de tiroides (CPT) parece asociarse con mayor riesgo de
persistencia/recurrencia. Fue referida en ciertas variantes del
mismo. No hay reportes en la población argentina. Objetivos:
1) Analizar la prevalencia de la mutación BRAF en el tejido
tumoral y no tumoral de pacientes operados por CPT y patología benigna; 2) Evaluar características clínico-patológicas en
CPT en relación a la mutación. Métodos: estudio prospectivo
en 25 pacientes operados consecutivamente. Se obtuvieron
muestras histológicas ≤0,5 cm de tejido nodular y adyacente
no nodular en fresco. Se extrajo ADN, se amplificó según
técnica ARMS (Amplification Refractory Mutation System)
Abstracts: Poster
PCR. Se analizó el patrón de bandas en gel de agarosa. Se efectuó secuenciación directa del gen en 4 muestras. Resultados:
46 análisis de BRAF en 13 pacientes operados por CPT y 12
por hiperplasia nodular coloide. 10/13 CPT (76,9%) resultaron BRAF+. Todas las muestras de tejido adyacente no tumoral respectivo y de patología benigna resultaron BRAF-. La
secuenciación directa confirmó los resultados. Los pacientes
BRAF+ tenían más edad en el momento del diagnóstico que
aquellos BRAF- (47,7 +/- 12,7 vs 24,7 +/- 8,1 años, p<0,01).
9/10 pacientes CPT BRAF+ correspondieron a variante clásica vs 0/3 en los BRAF- (p<0,02). Conclusiones: 1) La prevalencia de mutación del BRAF en esta población de CPT fue
elevada. 2) Más del 90% de CPT BRAF+ correspondió a la
variante clásica. 3) Los pacientes con CPT BRAF+ tenían más
edad en el momento del diagnóstico. 4) La mutación estuvo
ausente en la patología tiroidea benigna y en el tejido adyacente no tumoral.
Palabras clave: mutación BRAF; carcinoma papilar de tiroides; patología tiroidea benigna.
PO093 DREAM MUTATIONS MAY BE INVOLVED IN
PAPILLARY THYROID CARCINOMA DEVELOPMENT
Batista FA1; Bufalo NE1; Silva ACN1; Marcello MA1; Cardoso UO1;
Assumpção LVM1; Silva MJ2; Ward LS1
1
Laboratory of Cancer Molecular Genetics/University of Campinas
(GEMOCA/UNICAMP); 2Laboratory of Plants Molecular Genetics/University
of Campinas (UNICAMP) The downstream regulatory element antagonistic modulator
(DREAM) gene encodes a transcriptional repression protein
which interacts with calcium channels and also induces apoptosis. DREAM is involved in thyroid-specific gene expression,
acts as an endogenous intracellular effector of TSHR function that activates cAMP signaling and its increased expression has been associated with nodular gland development.
DREAM mutations have been described in a series of human
tumors, but its role in differentiated thyroid cancer (DTC)
is still unknown. We extracted DNA from tissue samples
(50 DTC patients - 48 papillary PTC) and 2 follicular thyroid
carcinomas (FTC); 50 benign thyroid nodules-colloid goiters
and peripheral blood (50 DTC patients - 36 PTC and 14 FTC;
50 healthy individuals), and sequenced exons 2, 3, 6 and 8 of
DREAM gene. Eight PTC patients and 1 patient with goiter but
none of the healthy individuals presented DREAM alterations.
There were 3 intronic alterations, 2 not previously described: 1
in intron 1 (IVS2-131) and 1 in intron 3 (IVS3+17) and another
one already described in intron 3 (IVS3+10). The alterations
IVS2-131 and IVS3+17 were found, each, in 1 patient with
PTC. The alteration IVS3+10, located in a regulatory region
and previously described in gastric cancer patients, was found
in 6 patients with PTC and in the 1 goiter patient. We did not
demonstrate any association between the observed alterations
and any clinicopathological features or with patient’s outcome.
However, these results suggest that DREAM gene may play a
role in papillary thyroid carcinoma development.
Keywords: thyroid cancer; DREAM; papillary thyroid carcinoma.
PO094 CHEMOKINES AS PROGNOSTIC MARKERS OF THE
PAPILLARY THYROID CARCINOMA
Francescantonio ICM1; Silva CMN1; Modesto DC1; Nunes LM1; Marques LRS1; Saddi VA1; Wastowski JI1 1
Pontifícia Universidade Católica/Goiás (PUC/GO) Background: The papillary thyroid carcinoma (PTC) is the
most common malignant tumor of the gland in countries
having iodine-sufficient or iodine-excess diets,and comprises about 80%-85% of thyroid malignancies.¹ Recent data
suggest that chemokines receptors (CXCR4, CCR7 and
CCR3) can play an important role in tumor aggressiveness, including tumor size, extrathyroidal extension (ETE),
angiolymphatic invasion (ALI) and lymph node metastasis.
(Wagner, et al. 2008). Objectives: We pretend to correlate
the CCR7 concentrate expression with metastasis occurrence. Methods: Paraffin embedded thyroid biopsies of 70
PTC patients (40 of whom had presented metastasis) were
evaluated. HLA-G-staining was observed in tumor cells
in PTC. Clinical and epidemiological data (sex, age, tumor
size, number of committed lymph nodes and the presence of
thyroid capsular invasion and sites of distant metastasis) were
obtained from medical archives. Results: Higher concentration of CCR7 were evidenced in the metastatic group instead
of the non-metastatic (p=0,0368). Conclusions: We evidenced that the higher concentration of CCR7 is a bad prognostic
marker of the papillary thyroid carcinoma. References 1. LiVolsi VA. Papillary thyroid carcinoma: an update. Modern Pathology.
2011; (24): S1-S9. 2. Wagner PL et al. The chemokine receptors CXCR4 and CCR7 are associated
with tumor size and pathologic indicators of tumor aggressiveness in papillary
thyroid carcinoma. AnnSurgOncol. 2008 Oct; 15 (10): 2833-41.
Keywords: papillary thyroid carcinoma; markers; prognostic.
Thyroid Nodule
PO095 VEGF EXPRESSION AND SONOGRAPHIC FEATURES
IN BENIGN THYROID NODULES ASSOCIATED TO
HASHIMOTO’S THYROIDITIS
Maia FFR1; Vassallo J2; Pinto GA3; Pavin EJ1; Matos PS4; Zantut-Wittmann DE1 1
Endocrinology Division/Department of Internal Medicine/UNICAMP;
2
Department of Pathology/Laboratory of Investigative and Molecular
Pathology/ CIPED/UNICAMP; 3Faculty of Medical Sciences/Laboratory of
Specialized Pathology, LAPE/CAISM/UNICAMP; 4Department of Pathology/
Faculty of Medical Sciences/UNICAMP Background: The molecular mechanisms regulating cell growth and cell death in thyroid adenomas are still poorly understood, in particular in cases associated to thyroid autoimmunity. Several studies have shown higher VEGF expression in
thyroid cancer tissues than in benign nodular area and normal tissues. Objectives: To investigate the expression of the
vascular endothelial growth factor (VEGF) in benign thyroid
nodules associated to Hashimoto’s thyroiditis (HT) and their
ultrasound (US) features correlation. Methods: We studied 55
benign thyroid nodules, 15 (27.3%) associated to HT (study
group) and 40 (72.7%) cases without HT (control group). The
nodular area (thyroid adenomas, TA) was staining for VEGF
and compared to peritumoral areas: normal adjacent tissue
(control group) and HT area (adjacent infiltrate lymphocytes;
study group). The VEGF staining data was semiquantified as
“weak” and “strong”, analyzed by descriptive and chi-square
tests. Results: VEGF was strongest detected in follicles of
nodular TA than HT area (p=0.006) and normal tissue (control group) (p<0.001). The multivariate analysis showed no
correlation between VEGF staining to clinical or lab variables
with strong correlation to suspect US features (central flow
and microcalcifications) in nodular area from control group
61
Abstracts: Poster
(p<0.001) versus HT’s group, which showed VEGF strong
expression correlated to irregular border (p<0.001) and central flow (p=0.032). Conclusions: VEGF was overexpressed in
follicles of nodular TA than HT’s and normal adjacent areas
with strong correlation to specific sonographic features in each
group of nodules, data not demonstrated in previous series.
Keywords: thyroid nodule; thyroid cancer; hashimoto’s
thyroiditis
Thyroid and Pediatric Disease
PO096 ASSOCIATION AMONG CTLA4, PTPN22 AND IFIH1
POLYMORPHISMS AND CHILDREN WITH GRAVES’ DISEASE
AND HASHIMOTO’S THYROIDITIS WITH OR WITHOUT TYPE
1 DIABETES
Bedin MR1; Trarbach EB1; Maciel LMZ2; Guerra-Jr G3; Queiroz M4;
Manna TD5; Damiani D5; Marui S1
1
Unidade de Tireoide/LIM 25/Disciplina de Endocrinologia e Metabologia/
HC/FM/USP; 2Departamento de Clinica Médica, Faculdade de Medicina
de Ribeirão Preto/Universidade de São Paulo (FMRP/USP); 3Departamento
de Pediatria/Faculdade de Ciências Médicas/Universidade Estadual de
Campinas (FCM/UNICAMP); 4Equipe Médica de Diabetes/Disciplina de
Endocrinologia e Metabologia/Hospital das Clínicas/Faculdade de Medicina/
Universidade de São Paulo (HC/FM/USP); 5Unidade de Endocrinologia
Pediátrica, Instituto da Criança, Hospital das Clínicas/ Faculdade de
Medicina/Universidade de São Paulo (HC/FM/USP)
Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are
thyroid autoimmune disorders (TAID) that infrequently affect
childhood. Early manifestation could be related to environmental and genetic background. CTLA4 and PTPN22 polymorphisms are widely studied, particularly in adults with
TAID but also with type 1 diabetes (DM1), independently of
HLA. Therefore, TAID and DM1 could share the same genetic
background. Recently IFIH1 A946T was associated with DM1
and HT, due to viral infection role in autoimmune triggering.
Objectives: Establish association among CTLA4, PTPN22 and
IFIH1 polymorphismsand children with GD, HT and DM1
with HT. Methods:Patients with GD, HT and DM1 diagnosed
<21 years-old were evaluated. All studied patients with DM1
had also HT. Adults with normal thyroid function, negative
anti-TPO and DM composed control group. DNA was extracted from peripheral leukocytes. CTLA4-318C/T, A49G and
CT60 polymorphisms, PTPN22 R620W and A946T IFIH1
were genotyped by real-time PCR. Results: Sixty patients were
diagnosed with GD (42 girls; x=11.3±4.4 years-old); 41 patients
with HT (35 girls; x=10 years-old±2.9); 22 patients with HT
and DM1 (12 girls; x=6 years-old at DM1 diagnosis and 10.2
years-old at HT diagnosis). All polymorphisms were in HardyWeinberg equilibrium.CTLA4A49G was only associated with
GD (p=0.049). PTPN22 was not associated with any group.
IFIH1 was only associated with DM1 and HT (p=0.007).
Conclusions: We found different genetic association among
patients with TAID, suggesting that children with TAID have
probably distinct genetic background.
Keywords: thyroid autoimmune disease; polymorphism;
childhood.
PO097 THE ACTIONS OF 3,5-DIIODOTHYRONINE, 3,5,3’–
TRIIODOTHYRONINE AND THYROXINE ON PAPILLARY
THYROID CARCINOMA CELL LINE VIABLITY
Coelho RG1; Carvalho DP1
1
Janeiro (IBCCF/UFRJ) 62
The expression of different deiodinases has attracted attention mainly in tumor models. Evidence suggests that abnormalities in the expression of type II (D2) and type III (D3)
deiodinases may modulate intracellular concentrations of
thyroid hormones (TH) influencing the cellular response.
Thus, our objective was to evaluate the effects of T3 and T2 on
the viability of tumoral cell lineages that differentially express
deiodinases. Initially, we evaluated the actions of exogenous
3,5-T2 on cell viability of NTHY (non-thyroid tumor) and
BCPAP (papillary thyroid carcinoma). After 48 hours in the
presence of T2 there was a reduction in cell viability measured by MTT assay in both cell lines with the highest effect
exerted on non-tumor cell. To assess whether the T2 would
promote some effect on the glycolytic metabolism, we evaluated glucose uptake and activity of hexokinase (HK) after 24
hours in different cells. The results show that glucose uptake
by NTHY is stimulated by 3,5-T2, unlike BCPAP, in which an
inhibition of approximately 60% was observed. No effects on
HK activity were observed after 24 hours of 3,5-T2 incubation in any of the cells evaluated. Then, we decided to evaluate
the effect of T4 and T3 in these cell types. By MTT assay, we
observed a direct effect of T4 on cell viability with 24 hours
of incubation in both NTHY and BCPAP. Given these results,
we conclude that: (1) T4 has a direct stimulatory effect on cell
death; and (2) 3,5-T2 has an effect on the glycolytic metabolism that is different between thyroid tumor cell (BCPAP)
and non-tumor cell (NTHY). These findings suggest a possible modulation of cell metabolism directly by T2 and T4
unlike T3.
Keywords: hormone thyroid; cancer; metabolism.
PO098 RADIOSENSIBILIZACIÓN DE LÍNEAS CELULARES
DE CÁNCER DE TIROIDES POR INHIBIDORES DE HISTONAS
DEACETILASAS
Perona M1; Thomasz L1; Rossich L2; Casal M1; Pisarev MA1; Juvenal G1 COMISIÓN NACIONAL DE ENERGÍA ATÓMICA; 2CONICET 1
Introducción: El tratamiento convencional del cáncer de
tiroides consiste en tiroidectomía total seguida de administración de 131I. Sin embargo, existe un número de pacientes que no responden con éxito a las terapias convencionales.
Objetivo: Estudiar la aplicación de inhibidores de histonas
deacetilasas (HDACI) como radiosensibilizadores para el
tratamiento del cáncer de tiroides. Procedimientos: Se cultivaron líneas celulares de cáncer humano tiroideo folicular
(WRO) y papilar (TPC-1). Se utilizaron los HDACI butirato
de sodio (NaB) y ácido valproico (AV). Se irradiaron las células con rayos gamma a diferentes dosis (1-8 Gy). Se evaluó la
acetilación de la Histona 3, el daño post-irradiación mediante
el ensayo de formación de colonias, la muerte celular, la distribución en el ciclo celular y el daño al ADN. Se evaluó la
capacidad de rediferenciar las células mediante la captación
de 125I, PCR y transfección transiente. Resultados: Ambos
compuestos hiperacetilaron la Histona 3. Los HDACI redujeron la fracción de sobrevida significativamente en las células WRO y TPC-1 de 68±1,6% a 42±3,8% (NaB) y a 56±0,01
(AV) y de 32,1±1,1% a 24,1±0,8% (NaB) y a 10,8±0,8% (AV).
Aumentó significativamente la muerte celular; el arresto celular en la fase G2/M en las WRO y en la fase G1 a las 24 horas
en las TPC-1 (AV) y el daño al ADN. No se observó un efecto
rediferenciador. Conclusiones: Los HDACI butirato de sodio
y ácido valproico funcionarían como radiosensibilizadores de
Abstracts: Poster
células de cáncer de tiroides. No se observó ningún efecto de
rediferenciación celular.
Palabras clave: Cáncer de tiroides; radiosensibilizador;
HDACI.
PO099 INFLUÊNCIA DE FAM83F, INTEGRANTE DE UMA
NOVA FAMÍLIA DE GENES TUMORAIS, NO CARCINOMA
ANAPLÁSICO DE TIREOIDE
Silva LR1; Fuziwara CS1; Kimura ET1
Instituto de Ciências Biomédicas/Universidade de São Paulo (ICB/USP)
1
Introdução: O carcinoma anaplásico é o mais agressivo dentre os histotipos de câncer de tireoide, sendo refratário à terapêutica convencional. A escassez de marcadores moleculares
diagnósticos e terapêuticos para esse tipo de câncer contribui
para sua alta letalidade, sendo necessário melhorar o entendimento da etiopatogênese e progressão tumoral. A análise
do genoma do câncer indicou desregulação da expressão de
FAM83F (previamente LOC113828). FAM83 é uma família
de proteínas que apresenta o domínio conservado DUF1669
com características putativas de atividade fosfolipase-D. No
entanto, seu papel funcional no câncer ainda permanece
pouco explorado. Assim, avaliamos a influência de FAM83F
no carcinoma anaplásico de tireoide. Métodos: A expressão de
FAM83F foi analisada por reação em cadeia pela polimerase
(polymerase chain reaction, PCR) em tempo real. Para superexpressar FAM83F, transfectamos o plasmídeo em linhagem
KTC2 de carcinoma anaplásico (KTC2-FAM83F). A proliferação celular foi avaliada por ensaio de contagem celular e a
migração celular foi investigada por ensaio de ferida (woundassay). Resultados: Observamos redução da expressão de
FAM83F na linhagem KTC2. A superexpressão de FAM83F
em KTC2-FAM83F resultou em modulação da proliferação e
migração celular. No ensaio de contagem celular, observamos
aumento de 27% no número de células KTC2-FAM83F após
72 h. Por outro lado, o ensaio de ferida revelou diminuição da
migração de células KTC2-FAM83F, observado pelo retardo
no tempo para fechamento da ferida. Conclusão: A superexpressão de FAM83F em KTC2 influencia a proliferação e
migração celular, indicando um potencial marcador tumoral
e alvo molecular a ser explorado no carcinoma anaplásico.
Palavras-chave: carcinoma anaplásico de tireoide; FAM83F;
câncer de tireoide.
PO100 AVALIAÇÃO DA EXPRESSÃO LIN28 “RNA BINDINGPROTEIN” E LET-7 NO CARCINOMA TIREOIDIANO
Olivé AN1; FuziwaraCS1; Kimura ET1 1
Instituto de Ciência Biomédica/Universidade de São Paulo (ICB/USP) Introdução: No carcinoma de tireoide (CT), ocorrem alterações na via MAPK em que a mais frequente é a mutação
no gene BRAFT1799A. A sinalização MAPK é modulada
por miRNA, pequeno RNA endógeno que apresenta expressão desregulada em carcinoma. No carcinoma papilífero de
tireoide-PTC, o miRNA LET-7, com atividade supressor
tumoral, apresenta-se pouco expresso. A biogênese deste
miRNA é controlada por proteínas ligantes de RNA LIN28.
Essas binding-protein ligam-se às formas primária e precursora de LET-7, inibindo o processamento. No entanto, o papel
de LIN28 na biogêneses de LET-7 no CT não é conhecido.
Objetivo: Avaliar o padrão de expressão de LIN28 e LET-7 no
carcinoma de tireoide. Metodologia: A expressão gênica de
LIN28 e do miRNA LET-7 foi avaliada por qPCR-tempo real
utilizando RNA-total das linhagens celulares humana de PTC
e carcinoma anaplásico de tireoide-ATC, na presença/ausência inibidor de BRAFV600E, PLX4032 (1 mM/mL) durante 24 h.
Resultados: Observamos aumento da expressão de LIN28B
nas linhagens de PTC (BCPAP) e ATC (KTC-2), ambas com
BRAFT1799A, assim como a redução na expressão do miRNA
LET-7. O bloqueio de BRAFV600E com PLX4032 resultou na
diminuição da expressão de LIN28 em ambas as linhagens.
Conclusão: A correlação inversa entre o aumento LIN28 e a
diminuição de LET-7 indica papel importante no carcinoma
tireoidiano com mutação BRAFT1799A.
Palavras-chave: LIN28; miRNA LET-7; RNA binding protein.
PO101 EFEITOS DO 17B-ESTRADIOL SOBRE A
GERAÇÃO DE H2O2 E EXPRESSÃO DE TGF-BETA E
METALOPROTEASES EM CÉLULAS PCCL3
Hecht F 1; Ortenzi VH1; Carvalho DP1; Fortunato RS1
1
Universidade Federal do Rio de Janeiro Introdução: A prevalência de disfunções tireoidianas é superior em mulheres e esse dimorfismo parece estar relacionado
à ação do estrogênio. A transdiferenciação das células epiteliais em células mesenquimais altamente móveis e apolares,
processo denominado transição epitélio-mesênquima (TEM),
foi descrito em tumores tireóideos. Moléculas como o TGF-b
e enzimas como as NADPH oxidases e metaloproteases possuem papel fundamental na TEM, estimulando esse processo.
Objetivos: Avaliar o efeito do estrogênio sobre a expressão e atividade das NADPH oxidases e a expressão de TGF- b, MMP-2
e MMP-9, envolvidas na TEM. Metodologia: Células PCCL3
foram incubadas por 72 h com diferentes concentrações de
17b-estradiol. O RNA foi obtido através do kit RNeasy®Plus
Mini Kit (Qiagen), seguindo as instruções do fabricante. A
análise da expressão gênica foi realizada por reação em cadeia
pela polimerase (polymerase chain reaction, PCR) em tempo
real utilizando SYBR green. A análise da geração de H2O2 foi
feita através do método AmplexRed/HRP. Resultados: Em
relação aos níveis de RNAm de MMP-2, TGF-b, NOX2 e
NOX4, observamos um aumento significativo nas células tratadas com estrogênio. Corroborando o aumento da expressão
das enzimas NOX2 e NOX4, o tratamento aumentou a geração de H2O2. Conclusão: Com base nesses resultados, concluímos que o tratamento com estrogênio foi capaz de aumentar a
expressão da NOX2 e NOX4, levando a um aumento da geração
de H2O2, e também a um aumento da expressão de TGF-b e
MMP2. Porém, mais experimentos são necessários para elucidar a interrelação entre o aumento de ERO e a expressão das
moléculas relacionadas à TEM.
Palavras-chave: thyroid; TGF- b; NADPH oxidase.
PO102 NÍVEL DE PARATORMÔNIO APÓS TIREOIDECTOMIA
TOTAL COMO PREDITOR DE HIPOCALCEMIA SINTOMÁTICA
– ESTUDO PROSPECTIVO
Gama RR1; Fezer GF1; Delfes RA1
1
Hospital Universitário Evangélico de Curitiba (HUEC) Introdução: Hipocalcemia é a complicação mais comum
após tireoidectomia total, sendo o hipoparatireoidismo
devido à injúria intraoperatória às paratireoides a principal
causa de hipocalcemia clinicamente relevante. Objetivo:
Avaliar a acurácia do PTH no pós-operatório imediato de
63
Abstracts: Poster
tireoidectomia total como preditor de hipocalcemia sintomática. Métodos: Trinta pacientes submetidos à tireoidectomia total ou totalização da tireoidectomia foram incluídos no estudo. PTH e cálcio total foram dosados na manhã
da cirurgia. PTH foi dosado novamente no pós-operatório
imediato (PTH-4 h). Cálcio total (Ca-72 h) e magnésio
(Mg-72 h) foram dosados 72 h após a cirurgia e hipocalcemia sintomática foi pesquisada. Resultados: Pacientes que
desenvolveram hipocalcemia sintomática tiveram níveis de
PTH-4 h, Ca-72 h, Mg-72 h significativamente menores e
declínio do PTH significativamente maior (p < 0,05) do que
os pacientes que não desenvolveram hipocalcemia sintomática. A sensibilidade, especificidade e acurácia de um PTH-4
h < 15 pg/mL em predizer hipocalcemia sintomática foram
de, respectivamente, 71,4%, 95,7% e 90%. Análise do PTH-4
h e do declínio do PTH com a curva ROC determinou que
um valor de corte de 6 pg/mL para PTH-4 h e de 88,9% para
o declínio do PTH obtiveram a melhor acurácia (93,3%),
com sensibilidade de 71,4% e especificidade de 100% em
predizer hipocalcemia sintomática. Conclusão: Nível de
PTH-4h inferior a 6 pg/mL e declínio do PTH superior a
88,9% apresentam alta acurácia em predizer hipocalcemia
sintomática pós-tireoidectomia total. Ambos podem ser
utilizados para rastrear pacientes propensos a desenvolver
esta condição clínica, a fim de iniciar precocemente a terapia de reposição com cálcio.
Palavras-chave: hipoparatireoidismo; hipocalcemia; tireoidectomia total.
PO103 ALTERAÇÕES METABÓLICAS E TIREOIDITE DE
HASHIMOTO
Ronsoni MF1; Ferreira L1; Oliveira MP1; Colombo BS1; Silva MC1;
Michels J1; Coral MHC1; Hohl A1
1
Universidade Federal de Santa Catarina (UFSC) Introdução: Tireoidite de Hashimoto (TH) é caracterizada
por falha progressiva na função tireoidiana e aumento de
TSH. Discute-se a associação entre TH e alterações metabólicas. Métodos: Foram avaliadas as variáveis clínico-laboratoriais de 53 pacientes com TH. Resultados: Os níveis de
TSH correlacionaram-se positivamente com colesterol total
(CT) (r=0,318; p=0,024) e LDL colesterol (r=0,298; p=0,036).
Níveis de T4 livre correlacionaram-se negativamente com CT
(r=- 0,297; p=0,036), LDL-C (r=- 0,351; p=0,013) e triglicerídeos (TGC) (r=- 0,319; p=0,021). HOMA-IR apresentou
correlação positiva com níveis de pressão arterial sistólica
(PAS) (r=0,482; p=0,003), diastólica (PAD) (r = 0,421; p =
0,012), insulina basal (r=0,973; p< 0,001) e Hb1AC (r=0,501;
p=0,007). Produto acúmulo lipídico (PAL) mostrou correlação positiva com circunferência abdominal (r=0,742;
p<0,001); IMC (r=0,577; p=0,006), PAS (r=0,457; p=0,037),
PAD (r=0,484; p=0,026), TGC (r=0,829; p< 0,001) e correlação negativa com anticorpo antitireoglobulina (anti-TGB)
(r=-0,536; p=0,015). Discussão: Os níveis de TSH e T4 livre
apresentaram associação com síndrome metabólica, o que
sugere aumento do risco cardiovascular. Mais estudos são
necessários para avaliar as associações com o anticorpo antiTGB. O índice PAL parece apresentar maior correlação metabólica entre as variáveis da SM quando comparado ao índice
HOMA-IR.
Palavras-chave: tireoidite de Hashimoto; alterações metabólicas; resistência insulínica.
64
PO104 CORRELAÇÃO ENTRE ALT, GGT E
CARACTERÍSTICAS CLÍNICAS E LABORATORIAIS EM
PORTADORES DE TIREOIDITE DE HASHIMOTO
Ronsoni MF1; Ventura A1; Canalli MHBS1; Hohl A1; Dantas-Corrêa EB1;
Schiavon LL1; Narciso-Schiavon JL1
1
Universidade Federal de Santa Catarina (UFSC) Introdução: Embora a disfunção tireoidiana tenha sido associada com algumas anormalidades hepáticas, há escassez de
informação sobre os fatores relacionados aos níveis de enzimas
hepáticas em portadores de tireoidopatias. Este estudo objetiva
correlacionar alterações de ALT e GGT com características clínico-laboratoriais de indivíduos com tireoidite de Hashimoto
(TH). Métodos: Estudo transversal com coleta prospectiva de
dados. A correlação entre os níveis de ALT e GGT com as foi
avaliada pelo coeficiente de correlação de Pearson. Resultados:
Analisados 56 pacientes com média de idade de 48,3±13,4 anos
(92,9% mulheres e 88,5% caucasianos). A média de IMC foi
28,0±5,3. Apresentaram níveis médios de ALT 37,6±11,8 U/L,
GGT 42,5±34,9 U/L, T4 livre 1,2±0,3 ng/dL e TSH 6,8±13,7
mU/L. Positividade para anticorpo antiperoxidase em 90,4%
e antitireoglobulina em 33,3%. Observou-se forte correlação
positiva entre ALT e os parâmetros: glicemia de jejum, triglicerídeos (TGC), ferritina e saturação de transferrina (p<0,001).
Quanto aos níveis de GGT, foi observada correlação positiva
com: TSH, TGC e ferritina (p<0,001), glicemia de jejum e colesterol total (p< 0,05). Com o teste do qui quadrado, observamos
que há uma tendência à associação entre TSH=3,0 mUI/L e
ALT (xLSN) (p=0,074). Conclusões: Em indivíduos com TH,
os testes bioquímicos hepáticos correlacionam-se a variáveis
relacionadas a alterações metabólicas e também a testes de
função tireoidiana. Os parâmetros relacionados ao controle
da doença tireoidiana devem ser levados em consideração ao
se interpretarem resultados dos testes bioquímicos hepáticos
nesses pacientes.
Palavras-chave: tireoidite de Hashimoto; alterações metabólicas; ALT, GGT.
PO105 SELECTIVE TREATMENT FOR
HYPOPARATHYROIDSM AFTER TOTAL THYROIDECTOMY
BASED ON PTH LEVELS
Bertelli AA1; Kikuchi W1; Derito CP1; Möller LG1; Hirota LN1; Garcia
VA1; Suehara AB1; Gonçalves AJ1; Menezes MB1
1
Faculdade de Ciências Médicas da Santa Casa de São Paulo Background: Hypocalcemia is the most common complication
after total thyroidectomy and the major determinant in delay
of discharge. Because of this, some authors routinely use oral
supplementation of calcium, while others postpone hospital
discharge waiting for multiple calcium dosages. Objectives:
Test a selective oral calcium/calcitriol supplementation to
avoid clinical manifestations of hypocalcemia based on parathyroid hormone levels after total thyroidectomy. Methods:
Prospective study with 31 patients undergoing total thyroidectomy or completion, with or without central neck dissection. Parathyroid hormone (PTH) was measured 1 hour
after postoperative period. Selective supplementation was
determined by serum PTH levels with oral calcium (PTH >5
pg/mL and <15 pg/mL) or oral calcium plus calcitriol (PTH
<5 pg/mL) and correlated with symptoms of hypocalcemia
during 10 days post thyroidectomy. Results: None of the
patients (14/31) with PTH levels >15 pg/mL developed symptoms (p=0,007). Among 17 patients with PTH <15pg/mL,
Abstracts: Poster
9 (52.84%) patients had adequate supplementation and
remained asymptomatic. Five patients (29.41%) had clinical manifestations without correct supplementation. Three
patients developed symptoms taking correct supplementation (p=0,009). Conclusions: The selective supplementation
based on post thyroidectomy PTH levels can be used safely to
avoid clinical manifestations of hypocalcemia. References: 1. Jumaily JS, Noordzij JP, Dukas AG, Lee SL, Bernet VJ, Payne RJ, McLeod IK,
Hier MP, Black MJ, Kerr PD, Raffaelli M, Bellantone R, Lombardi CP, Dietrich
MS. Prediction of hypocalcemia after using 1 to 6 hour postoperative parathyroid hormone and calcium levels: an analysis of pooled individual patient
data from 3 observational studies. Head Neck. 2010; 32 (4): 427-34.
Keywords: hypoparathyroidism; parathyroid hormone;
thyroidectomy.
PO106 ASSOCIATION OF TSH LEVEL TO METABOLIC
AND ANTHROPOMETRY PARAMETERS IN OVERWEIGHT
EUTHYROID ADOLESCENTS
Souza LL1; Guedes EP1; Moreira RO2; Godoy-Matos AF2; Vaisman M3 1
Instituto Estadual de Diabetes e Endocrinologia (IEDE), Universidade
Federal do Rio de Janeiro (UFRJ); 2Instituto Estadual de Diabetes e
Endocrinologia (IEDE);3Universidade Federal do Rio de Janeiro (UFRJ) Background: The prevalence of obesity in adolescents is
increasing and is associated to diabetes mellitus, hypertension and dyslipidemia. Nowadays, there is little data about
levels of thyroid-stimulating hormone (TSH) in euthyroid
adolescents and its association with metabolic disarrangement. Objectives: To investigate the correlation between
TSH levels and metabolic and anthropometric parameters in
overweight/ obese euthyroid adolescents. Methods: We evaluated 172 (75 male/135 female) pubertal adolescents with
overweight/obesity [body mass index (BMI) > percentile 85],
aged 12-18 years. Anthropometric, biochemical and hormonal analysis were performed. Results: Patients were divided
into 2 groups based on TSH levels: a group had TSH levels <
2.5 mU/L (n=61/35,47%) and another group had TSH levels ≥
2.5 mU/L (n=111/64,53%). Waist-to-hip ratio (p=0,032) and
HOMA-IR (p=0,020) were significantly higher while HDLcholesterol (p=0,026) were significantly lower in patients with
TSH levels ≥ 2,5 mU/L. A trend for significance was observed
for waist circumference and TSH levels ≥2,5 mU/L (p=0,062).
There was no correlation among TSH levels and age (p=0,34),
BMI (p=0,10), fasting plasma glucose (p=0,53), triglycerides
(p=0,24) and LDL-Cholesterol (p=0,46). Conclusions: In
overweight/obese euthyroid adolescents there was a correlation between TSH levels in the upper normal range (2.5-5.0
mU/L) with waist-to-rip ratio, HOMA-IR and lower HDLcholesterol levels, increasing the risk of metabolic derangements. Therefore, a TSH level <2.5 mU/L may be associated
with a favourable metabolic profile, however the question
about use of thyroid hormone to achieve the target of TSH
levels <2.5 mU/L needs to be investigated.
Keywords: adolescents; euthyroid; overweight.
Multinodular Goiter
PO107 A GIANT GOITER: AN ILLUSTRATIVE CASE
Alcântara ANS1; Silva PSA1; Ferraz TMBL1; Macedo RBL1;
Amaral SS1; Muniz AA1
1
Hospital Geral de Fortaleza (HGF) Background: Goiter occurrence is rare in non-endemic
areas of iodine deficiency. Substernal presentation is unusual,
usually resulting from multi-nodular goiter. Objectives: To
illustrate a case of a patient with a symptomatic giant goiter
in a non-endemic area of iodine deficiency with a proposed
surgical treatment. Methods: Medical record analysis of a
patient hospitalized in the Endocrinology Unit of the HGF,
Ceará, Brazil. Results: A 66-year-old woman was admitted
for a huge neck swelling and worsening dyspnea. She denied
dysphagia or odynophagia. She reported euthyroid goiter for
10 years, refusing surgery until now. On examination, she was
hoarse, respiration was 18 per minute, lungs were clean and
the thyroid gland was enlarged, smooth, lobulated and moved
with swallowing. Laboratory test demonstrated thyrotropin
0,349 mU/mL (range 0,4-4,5), free T4-1,31 ng/dL and thyroid
antibodies not detectable. Cervical and mediastinal computer
tomography scan showed a huge asymmetric multi-nodular
goiter, measuring 16,5x14,6x9,6 cm, extending from posterior wall of oropharynx and hypopharynx to mediastinum,
with external compression of trachea and esophagus, reducing lumen and of right subclavian vein. Thyroid scintigraphy showed marked overall reduction of uptake in thyroid
bed, consistent with advanced degree multi-nodular goiter.
Fine-needle aspiration biopsy in the right lobe was benign.
Total thyroidectomy was decided. The gland size was sufficient to produce thyroid hormone, showing subclinical
hyperthyroidism, even not having a hyperfunctional scintigraphy. Conclusions: This case reminds us of the rarity of finding a benign giant goiter in 21st century in a non-endemic
area of iodine deficiency.
Keywords: goiter; giant; substernal.
Hyperthyroidism
PO108 AVALIAÇÃO DA RESPOSTA À IODOTERAPIA NO
TRATAMENTO DO HIPERTIREOIDISMO DA DOENÇA DE
GRAVES
Gama MPR1; Raymundo AR1; Costa CF1; Debortoli J1; Gama RR1
Hopsital Universitário Evangélico de Curitiba (HUEC) 1
Introdução e objetivo: A iodoterapia é comumente empregada no tratamento da doença de Graves; o objetivo deste
estudo foi avaliar a sua efetividade no tratamento de pacientes
com doença de Graves, atendidos em uma instituição universitária. Método: Foram analisados 113 prontuários de pacientes atendidos no Serviço de Endocrinologia do HUEC, entre
janeiro de 1993 e dezembro de 2007. Foram selecionados
pacientes submetidos à iodoterapia em algum momento do
seu tratamento (n=44). Resultados: Observou-se prevalência do sexo feminino (89%) e a idade média do grupo foi de
39,6 anos. Dos 44 pacientes submetidos à iodoterapia, 37 (84%)
fizeram algum tipo de tratamento anterior, tendo a maioria, 32
pacientes (72,7%), sido submetida a tratamento medicamentoso prévio. Após serem submetidos à iodoterapia (n=44),
73% dos pacientes obtiveram resposta; sendo que 28 (87,5%)
desenvolveram hipotireoidismo e 4 (12,5%) desenvolveram
eutireoidismo. Oito pacientes (18%) não obtiveram resposta,
persistindo com hipertireoidismo mesmo após a utilização de
I-131. A dose média daqueles que não responderam foi de 9,77
mCi e a dose média daqueles que responderam ao tratamento,
13,79 mCi (p=0,03). Conclusão: A dificuldade em induzir resposta terapêutica é constatada pelo fato de mais da metade dos
pacientes ter necessitado de associação de tratamentos para
obtenção do controle clínico e laboratorial da doença. Quanto
65
Abstracts: Poster
maiores as doses de I-131, maiores são as taxas de resposta de
controle da doença de Graves.
Palavras-chave: doença de Graves; hipertireoidismo; iodoterapia.
PO109 MARROW HYPOPLASIA: A RARE COMPLICATION OF
UNTREAT GRAVES DISEASE
Rodrigues BS1; Garcia JCA1; França LBC1; Torrini RC1; Caldas D1;
Campos CFC1
1
Instituto Estadual de Diabetes e Endocrinologia (IEDE) Pancytopenia is a rare but serious complication of thyrotoxicosis. Hyperthyroidism affects in several ways the hematopoiesis, but its pathogenesis is still unclear. Imunological
mechanisms have been suggested to be involved as antineutrophil and antiplatelet antibodies. Despite of the majority
cases reporting pancytopenia in Grave’s disease associated
with a hypercellular bone marrow with periferic destruction,
this case is about a bone marrow hypocellular without fibrosis or fat tissue replacement. Female patient, 55-years-old,
was admitted with pancytopenia in the diagnosis of Grave’s
disease. Because of the hematologic alteration we chose
not to start antithyroid drugs (guidelines 2009) and started
lithium (900 mg/day). The patient developed severe neutropenia without fever being submitted to radioiodine (131-I),
with progressive worsening of neutropenia. Bone marrow
biopsy and serologic markers was required to rule out other
etiologiesand then was started granulocyte stimulating factor
(G-CSF). All tests for the differential diagnosis of hematologic disease were negative and bone marrow biopsy revealed
hypocellularity without marrow infiltration or replacement
by fibrous or fatty tissue secondary to underlying disease.
The response to G-CSF with improvement of pancytopenia
occurred in 8 days associated with progressive decrease of
thyroid hormones. So, we suggest that patients with Grave’s
disease and hematologic significant alteration, with other
causes ruled out by laboratory tests, should be evaluated by
a hematologist regarding performing bone marrow biopsy
for definitive diagnosis before starting treatment for thyroid
disease. References 1.Lima CS, Zantut Wittmann DE, Castro V, Tambascia MA, Lorand-Metze I,
Saad ST, Costa FF et al. Pancytpenia in untreated patients with Graves Disease.
Thyroid. 2006; 16: 403-9. 2. Shaw B, Mehta AB et al. Pancytopenia responding to treatment of hyperthyroidism: a clinical case and review of the literature. Clin Lab Haematol.
2002 Dec; 24 (6): 385-7.
Keywords: pancytopenia; hypoplasia; graves disease.
PO110 AGRANULOCITOSE INDUZIDA POR METIMAZOL EM
PACIENTE COM DOENÇA DE GRAVES
Foppa A1; Alves JM2; Dos Santos EC1; Dos Santos AA1; Fiorin D3;
Teixeira NM3; de Carvalho GA3
1
Hospital de Clínicas da Universidade Federal do Paraná (HC/UFPR);
2
Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da
Universidade Federal do Paraná; 3 Serviço de Endocrinologia e Metabologia
do Hospital de Clínicas da Universidade Federal do Paraná
Os efeitos adversos hematológicos das drogas antitireoidianas são reações graves. Apesar disso, o prognóstico dos
pacientes melhorou com o avanço da terapia de suporte. O
objetivo deste trabalho é relatar um caso de agranulocitose
secundária ao tapazol, desencadeando neutropenia febril.
Paciente feminina, 48 anos, com diagnóstico recente de
hipertireoidismo, em uso de metimazol 30 mg/dia iniciado
66
40 dias antes da admissão; quando procurou atendimento
por odinofagia, tinha febre há 1 mês. Exames laboratoriais
mostraram anemia, leucopenia com agranulocitose (leucócitos: 690/mm3; neutrófilos: 0), TSH suprimido, T3 total:
311,2 ng/dL, T4 livre: 2,64 ng/dL e todos os anticorpos
tireoidianos positivos, inclusive o TRAB. Sorologias para
HIV, hepatites, vírus Epstein Barr e citomegalovírus negativas; biópsia de medula óssea normal. Após 9 dias de suspensão do metimazol, a paciente evoluiu com normalização
do hemograma e boa resposta à antibioticoterapia de amplo
espectro. Após resolução do quadro infeccioso, foi realizada
iodoterapia para tratamento definitivo, apresentando normalização dos níveis de T3 total e T4 livre. A agranulocitose
é uma condição rara, porém grave da terapia com tionamidas, com prevalência de 0,1%-0,5% e usualmente ocorre nos
primeiros 2 meses de tratamento. A recuperação leva alguns
dias, mas pode ocorrer grande morbimortalidade decorrente de infecções. É recomendado que seja realizada dosagem diferencial de leucócitos precocemente caso ocorra
odinofagia ou outro sinal de infecção. Logo que detectado
o evento adverso, a droga deve ser suspensa mesmo que o
paciente esteja assintomático, e faz-se necessário realizar o
tratamento definitivo da doença. Se houver febre, é mandatório iniciar antibioticoterapia de amplo espectro.
Palavras-chave: doença de Graves; agranulocitose; metimazol.
PO111 DOENÇA AUTOIMUNE DA TIREOIDE: DO HIPO AO
HIPERTIREOIDISMO – RELATO DE CASO
Rocha AM1; Pontes AAN1; Capote Júnior JRFG1; Sena CM1; Torres
MR1; Pequeno TA1; Rocha BAM2
1
Hospital Universitário Alcides Carneiro/Universidade Federal de Campina
Grande (HUAC/UFCG); 2Universidade Federal de Pernambuco Introdução: As doenças autoimunes da tireoide (doença de
Graves e a tireoidite de Hashimoto) são comuns, manifestando-se clinicamente por um largo espectro de alterações clínicas e laboratoriais, podendo variar de hipo a hipertireoidismo
no mesmo doente e evoluir de uma para outra. Objetivo:
Relatar um caso de doença autoimune da tireoide evoluindo
com hipertireoidismo 6 anos após tratamento do hipotireoidismo. Metodologia: Revisão do prontuário da paciente de 37
anos, sexo feminino, parda, professora, com queixas de ganho
de peso, astenia e edema de MMII e face há 1 mês. Ao exame
físico: IMC: 35,51 kg/m² e bócio difuso. Os exames mostravam: TSH > 100 mUI/mL (VR: 0,3-4,2mUI/mL); T4 livre: 0,29
ng/dL (VR: 0,8-1,9 ng/dL); anti-TPO:472,5 UI/mL. Iniciado
levotiroxina 25 mg/dia, com aumento gradual até 100 mg/dia.
Após 6 anos, a medicação foi reduzida e descontinuada por
apresentar palpitações, tremores, ansiedade, labilidade emocional, intolerância ao calor e perda de peso. Ao ultrassom,
a tireoide era aumentada com textura heterogênea. TSH <
0,004 mUI/mL; T4 livre: 4,53ng/dL; anti-TPO>600; TRAb: 40
UI/mL (VR: >1,75); à cintilografia de tireoide, bócio difuso
hiperfuncionante com captação das 24 h de 70%. Após 3
meses usando Tapazol® 30mg/dia, evoluiu com proptose à
direita, exoftalmometria OD: 21mm; OE: 15mm. Discussão e
conclusão: A evolução espontânea de doença de Graves com
hipertireoidismo para hipotireoidismo está bem documentada e o inverso, embora mais raro, pode ocorrer. Ressalte-se
Abstracts: Poster
a importância da vigilância periódica dos pacientes com
doença autoimune tireoidiana considerando-se a variabilidade da expressão clínica da doença a longo prazo e o risco
do hipertireoidismo não diagnosticado.
Palavras-chave: hipotireoidismo; hipertireoidismo; doença
autoimune.
Hyperthyroidism
PO112 THYROTOXIC CRISIS SUPERIMPOSED TO LIVER
DISEASE: REPORT OF 2 CASES
Macedo LML1; Silva PSA1; Coelho SFM1; Amaral SS1; Acântara ANS1;
Costa MCM1
1
Hospital Geral de Fortaleza (HGF)
Introduction: Thyrotoxic crisis (TC) is one of the most
critical endocrine emergencies. It affects <10% of those
admitted for thyrotoxicosis with a mortality of 20%-30%.
Hyperthyroidism can exacerbate and perpetuate liver dysfunction caused by other etiologies. Objective: Describe 2
case reports of TC superimposed to liver disease. Methods:
Review of medical records of 2 patients admitted to the
emergency unit of HGF. Results: Case 1 – Man, 40, hospitalized for jaundice and symptoms of hyperthyroidism.
History of congestive heart failure and atrial fibrillation.
Had exophthalmos, tremor of the extremities, Plummer’s
nail, without apparent thyroid goiter. Ex-alcoholic. Exams:
TSH 0.04 mU/L, FT4>6 hg/dL, positive antithyroid antibody, negative serology for hepatitis, increase in transaminases and important hyperbilirubinemia. US thyroid:
changes suggestive of thyroid disease. Endoscopy: esophageal varices caliber. He was held without antithyroid drugs
(ATD), propranolol and started carbolitium. He evolved to
TC and severe sepsis. Started propylthiouracil and hydrocortisone. Plasmapheresis for subsequent embolization of
thyroid arteries was decided. There was clinical and laboratory improvement after two sessions (FT4 3.31 ng/dL). Was
not performed thyroid artery embolization due to clotting
disorder and current infection. Patient died due to severe
sepsis. Case 2 – Male, 29 years-old, alcoholic, admitted for
ascites framework., Initiated 1 month ago, typical signs and
symptoms of hyperthyroidism 3 years ago. Presented jaundice, exophthalmos, signs of chronic liver disease, thyroid
goiter, tachycardia and irregular heart rhythm. Exams: TSH
0.01 mU/L, FT4 4.25 ng/dL, elevated transaminases and bilirubin, negative hepatitis serologyand positive antithyroid
antibodies. US abdomen: signs of chronic liver disease and
ascites. US thyroid: increase and diffuse heterogeneous
echotexture. Treatment with propranolol, dexamethasone
and propylthiouracil; suspended 22 days after this, because
increased transaminases, with subsequent introduction
of tapazol. Improved clinically the hyperthyroidism, but
patient died due to sepsis. Conclusion: The diagnosis and
appropriate management of TC is vital to prevent high mortality. Thyrotoxicosis has been associated with liver abnormalities and multiple coexisting factors such as ICC, malnutrition, autoimmune diseases or treatment with DAT. Other
alternative therapies may be useful in addressing these critical patients, such as plasmapheresis and embolization of
thyroid arteries.
Keywords: hyperthyroidism; thyrotoxic crisis; liver dysfunction.
PO113 SUCCESS RATES IN GRAVES’ DISEASE WITH A
SINGLE LOWER RADIOIODINE DOSE
Huachin Soto MK1; Norieha Ruiz VH1; Torres Samame LDR1; Molina
Calderon GI
1
Cayetano Heredia Hospital/Cayetano Heredia University; 2Santiago
Apóstol Medical Center Background: Graves’ disease (GD) is commonly treated with
radioiodine (RD) dose. Higher doses increase success rates,
but few studies assess the time to treatment success after a
single lower RD dose. Objetive: To describe clinical course
of patients with GD who were administered an empirically
RD dose as treatment. We focused the time when stable EU
or hypothyroidism was achieved. Methods: Medical records
of all patients with GD between 1999 and 2011 of a general
hospital were reviewed. Diagnosis of GD was made with elevated free T4, total T4 or total T3, suppressed TSH, thyroid
autoantibodies and clinical examination. We divided them in
2 groups, G I: <10 mCi and G II: ≥10-≤15 mCi. Successful
treatment (ST) post RD was defined as hypo or euthyroidism
without AD after a single RD dose. Results: There were 77
patients with GD. Ablative dose of RD was received in 51
patients (66%), 23 patients were either lost to follow up or
still undergoing AD. Available data of 28 (55%) patients were
described. Mean age was 37.18 years, 78.6% female, previous
AD treatment was 64.3%, mean thyroid mass were 62.7 gr
and 88.3 gr in G I and II, respectively. ST was the same in
both groups (85.7%), mean time to remission was similar
in both groups,17.6 and 18.3 months in G I and II, respectively. Conclusions: No difference was evidenced in ST rate
and time to remission in lower and higher RD dose. Lower
RD dose (<10 mCi) in small thyroid gland can be used.
Keywords: graves; radioiodine; hyperthyroidism.
PO114 CRISE TIREOTÓXICA E FALÊNCIA HEPÁTICA
FULMINANTE: RELATO DE CASO E REVISÃO DA
LITERATURA
Contrucci AC1; Santomauro ATMG2; Paula CA2; Fraige Filho F2; Arçari
GD2; Carvalho ITI2; Magalhães JF2; Capps LM1; Silva PPB2; Bacchin RP2
1
Faculdade de Medicina do ABC (FMABC); 2Beneficência Portuguesa de São
Paulo
Crise tireotóxica é uma apresentação grave de tireotoxicose,
com taxa de mortalidade de até 30%. A falência hepática fulminante (FHF) é uma complicação rara e grave da tireotoxicose. Caracteriza-se pelo desenvolvimento de dano hepático
com diminuição da capacidade sintética e encefalopatia em
pacientes com função hepática, prévia, normal, com taxa
de mortalidade em torno de 60%. Nossa paciente foi admitida com quadro de crise tireotóxica associada à FHF, sendo
necessário ser submetida à tireoidectomia total e transplante
hepático, com boa evolução clínica. Em revisão de literatura,
encontramos outros 7 casos de crise tireotóxica associada à
FHF. Dentre os oito casos, 2 evoluíram a óbito, e apenas 3
foram submetidos à tireoidectomia e transplante hepático
concomitantes, seguindo com boa evolução clínica e recebendo alta hospitalar dentro de 10 dias após a cirurgia. Tanto
a crise tireotóxica como a FHF apresentam, independentemente, altas taxas de mortalidade, e o manejo de pacientes
com as 2 condições é um grande desafio. Sendo assim, sabendo-se que a disfunção hepática pode ocorrer em portadores
de hipertireoidismo, devemos nos atentar para a avaliação
da função hepática nesses pacientes e para o rápido declínio
desta em pacientes com crise tireotóxica. Nos pacientes que
67
Abstracts: Poster
se apresentaram com esta rara condição clínica, devemos
considerar a realização de tireoidectomia total associada a
transplante hepático.
Palavras-chave: crise tireotóxica; tireotoxicose; falência
hepática fulminante.
PO115 HIPERTIREOIDISMO CAUSADO PELA DOENÇA DE
GRAVES EM PACIENTE PORTADOR DE DOENÇA RENAL
CRÔNICA TERMINAL: RELATO DE CASO
Satomauro ATMG1; Paraguassu BR1; Paula CA1; Fraige Filho F1; Vieira
MCC1; Dallal MVS1; Pereira NGB1; Valle PO1; Costa PS1; Correa RC1
1
Beneficência Portuguesa de São Paulo Paciente do sexo feminino, 44 anos, com história clínica de
doença renal crônica (clearence de creatinina=25 mg/dL)
em tratamento conservador, encaminhada ao nosso serviço
para avaliação e tratamento de hipertireoidismo recémdiagnosticado. Relatava perda ponderal de 6 kg em 2 meses,
palpitações e aumento do volume cervical. Ao exame físico,
apresentava frequência cardíaca (FC): 114 bpm, tremores de
extremidades, sudorese palmar e aumento do volume tireoidiano, sem sopro audível. Em avaliação laboratorial, apresentava TSH< 0,001 mU/L, T4 livre=4,36 ng/dL,TRAB=24%.
Ultrassonografia (USG) de tireoide mostrou aumento difuso,
com volume=33 cm3, hipervascularização da glândula. A
cintilografia de tireoide mostrou captação de 73% em 24
h. Inicialmente a paciente foi medicada com Metimazol 30
mg/dia, e após 30 dias, apesar da melhora da função tireoidiana (T4 livre=1,67 ng/dL), houve piora da função renal,
sendo necessário suspender a medicação, iniciar hemodiálise
e indicar iodoterapia, que, para esta paciente, foi de 15 mCi
de I-131. Visto que a excreção do iodo se dá principalmente
pelos rins, muitas questões surgem em pacientes em diálise,
como a dose a ser administrada e o tempo ideal para diálise
após a administração do iodo. Até o momento, menos de 20
casos semelhantes foram relatados na literatura, e, embora a
dose de iodo não precise ser ajustada à função renal, a primeira diálise pós-iodo dever ser postergada até que ocorra a
absorção máxima de iodo pela tireóide, em torno de 10 h.
Palavras-chave: hipertireoidismo; doença de Graves; insuficiência renal crônica.
Hypothyroidism
PO116 AVALIAÇÃO DA RELAÇÃO DE DOSAGENS SÉRICAS
DE HORMÔNIO TIREOESTIMULANTE COM GÊNERO E
IDADE EM UM GRUPO DE INDIVÍDUOS DE GOIÂNIA, GOIÁS,
BRASIL
Almeida AR1; Melo MA1; Botacin LS1; Ferro LM1; Miranda TMT1; Francescantonio ICCM1; Rezende KN1 1
Pontifícia Universidade Católica de Goiás (PUC/GO) Introdução: Doenças associadas às alterações do hormônio
tireoestimulante (TSH) têm alta prevalência na população
mundial. Uma das principais alterações é o aumento do TSH,
que desencadeia hipotireoidismo devido a uma deficiência
quantitativa de tri-iodotironina e tiroxina. Por outro lado, a
diminuição de TSH pode resultar em hipertireoidismo. Em
São Paulo, Brasil, foi demonstrado que o hipotireoidismo
ocorre em 5,9% das mulheres e 5,4% dos homens, enquanto
o hipertireoidismo tem menor prevalência (mulheres – 0,7%,
e homens – 0,4%). Objetivo: Analisar a relação de dosagens
séricas de TSH com gênero e idade em um grupo de indivíduos residentes em Goiânia, Goiás, Brasil, em 2012. Métodos:
68
Realizou-se um estudo transversal com 742 pacientes que
fizeram dosagens de TSH, selecionados ao acaso do banco
de dados do Laboratório da Área de Saúde da PUC/GO.
Destes pacientes, 528 pertenciam ao gênero feminino e 214
ao masculino, ambos com idades variando de 2 a 90 anos. Os
dados de TSH, gênero e idade foram tabulados e analisados
utilizando-se o programa Microsoft® Excel 2010. Resultados:
Dos 742 pacientes, 111 (14,96%) tiveram dosagens elevadas
de TSH, sendo maior a frequência em mulheres (63,08%) e
na faixa etária de 40 a 59 anos (44,54%). Apenas 6 pacientes (0,81%) apresentaram baixas dosagens de TSH, sendo a
maioria também mulheres (83,33%) e com idades variando
entre 40 e 59 anos (50,00%). Conclusões: Neste grupo analisado, observou-se uma maior prevalência de hipotireoidismo,
sendo maiores os percentuais em indivíduos do gênero feminino com idades entre 40 e 59 anos.
Palavras-chave: TSH; hipotireoidismo; epidemiologia.
PO117 PREVALÊNCIA E DIAGNÓSTICO PRECOCE
DE HIPOTIREOIDISMO SUBCLÍNICO, UTILIZANDO-SE
DIFERENTES VALORES DE REFERENCIA PARA TSH, EM
GOIÂNIA, GOIÁS, BRASIL
Normanha LL1; Ribeiro RX1; Leão JRB1; Vento L1; Vieira MB1; Miranda
TMT1
1
Introdução: O hipotireoidismo subclínico (HSC) caracteriza-se como um estado sem sintomas clássicos de hipotireoidismo, com níveis séricos normais de hormônios tireoidianos, porém aumentados de hormônio estimulante da tireoide
(TSH). Oscilações nas dosagens de TSH representam o parâmetro laboratorial mais sensível para o diagnóstico precoce
da disfunção tireoidiana. Nos últimos anos, diferentes estudos preconizaram para o TSH valores de referência (VR)
variando de 0,3 a 5,5 mIU/L ou de 0,2 a 4,5 mIU/L. Entretanto,
esses padrões de normalidade têm sido questionados, sendo
sugerido recentemente 3,5 mIU/L como limite superior para
o TSH. Objetivo: Avaliar a prevalência de HSC, utilizando-se diferentes VR para TSH, em um grupo de indivíduos
atendidos em evento comunitário da PUC/GO. Métodos:
Realizou-se um estudo transversal descritivo com 170 pacientes, nos quais foi feito exame físico da glândula tireoide, além
da coleta de amostras sanguíneas para dosagens séricas de
TSH e T4 livre. Fez-se análise dessas variáveis para o diagnóstico de HSC, fixando o VR de T4 livre em 0,7 a 1,8 ng/dL.
Resultados: Dos 170 pacientes, 47 (27,6%) foram diagnosticados com HSC, considerando limite superior de 3,5 mIU/L,
enquanto que 33 (19,4%) a partir do VR até 4,5 mIU/L e 17
(10,0%), quando se usou VR até 5,5 mIU/L. Pode-se considerar que a faixa de índices sabidamente anormais está concentrada entre 4,5 e 5,5 mIU/L. Conclusão: Foram observadas
variações nos índices de prevalência de HSC, ressaltando a
necessidade da padronização adequada de VR para TSH para
obtenção de um diagnóstico preciso de HSC.
Palavras-chave: hipotireoidismo; hormônio estimulador da
tireoide; valores de referência.
PO118 AVALIAÇÃO DOS ÍNDICES HEMATIMÉTRICOS
DE PACIENTES COM HIPOTIREOIDISMO SUBCLÍNICO
ATENDIDOS EM EVENTO COMUNITÁRIO EM GOIÂNIA,
GOIÁS, BRASIL
Ribeiro RX1; Normanha LL1; Leão JRB1; Vento L1; Vieira MB1; Francescantonio ICCM1; Miranda TMT1
1
Pontifícia Universidade Católica de Goiás (PUC/GO) Abstracts: Poster
Introdução: O hipotireoidismo subclínico (HSC) caracteriza-se pela combinação dos níveis séricos do hormônio
estimulante da tireoide (TSH) elevado e T4 livre normal.
Variações na dosagem inicial de TSH representam importante fator de evolução do HSC para o hipotireoidismo.
Estima-se que este possua maior prevalência entre as mulheres (2,0%) que nos homens (0,2%), podendo causar redução
generalizada dos processos metabólicos em ambos. Em mais
de 30,0% dos casos, observa-se quadros de anemia microcítica/hipocrômica, normocítica/normocrômica ou macrocítica/normocrômica. Objetivo: Analisar relação entre índices
hematimétricos de pacientes com HSC atendidos em evento
comunitário realizado em Goiânia, Goiás, Brasil. Métodos:
Realizou-se um estudo transversal descritivo com 143 pacientes, dos quais foi feita a análise dos resultados das dosagens de
TSH e T4 livre para diagnóstico de HSC e posterior comparação com os achados do hemograma. Resultados: Dos 143
pacientes, 27 (18,9%) apresentaram HSC, sendo a maioria, 20
(74,1%), do gênero feminino. Dentre estas, 5 (25,0%) desenvolveram anemia, sendo 3 do tipo normocítica/normocrôica
e 2 microcítica/hipocrômica. Apenas 1 (14,3%) paciente do
gênero masculino teve anemia normocítica/normocrômica.
Utilizando-se o coeficiente de Pearson, observou-se correlação
moderada positiva entre hemácias e TSH (índice de 0,6372);
correlação fraca positiva entre hematócrito e hemoglobina
com TSH (índices de 0,3059 e 0,1367, respectivamente); correlação fraca negativa entre VCM e HCM com TSH (índices
de -0,3724 e -0,3482, respectivamente); e relação íntima negativa entre CHCM e TSH (índice de -0,0896). Conclusão: Os
índices hematimétricos dos pacientes com HSC e TSH foram
indiretamente proporcionais, porém houve relação moderada
positiva com hemácias, mostrando ser diretamente proporcional, necessitando de maiores investigações.
Palavras-chave: hipotireoidismo; anemia; tireoide.
PO119 RELAÇÃO ENTRE TSH, CREATININA E UREIA
Francescantonio ICM1; Rezende KN1; Borges ALF1; Francescantonio
ICCM1
1
Introdução: As nefropatias crônicas podem se apresentar
com quadros que simulam o hipotireoidismo, incluindo
níveis reduzidos de T3-T4, devido, à redução da globulina ligadora da tiroxina (thyroxin binding globulin, TBG).
Pacientes hipotiróideos frequentemente apresentam reduções da filtração glomerular e do fluxo plasmático renal.
Objetivo: Investigar a relação entre hormônio estimulante da
tireoide (TSH),creatinina e ureia de pacientes atendidos em
um Laboratório de Análises Clínicas em 2012, em Goiânia,
GO. Métodos: Foi realizado um estudo transversal com 531
pacientes, 73,2% feminino e 26,8% masculino, entre 7 e 83
anos. As variáveis foram: sexo, idade, TSH (0,27 a 4,2 mIU/
mL), creatinina (0,4-1,2 mg/dL) e ureia (15-45 mg/dL).Os
dados foram tabulados em planilha do Microsoft® Excel 2007
e analisados pelo teste Manny Withney. Resultados: A análise
estatística não apresentou resultados significantes. No sexo
feminino, o grupo com TSH dentro da referência apresentou
médias de creatinina de 0,9 mg/dL e ureia de 32,18 mg/dL. O
grupo com TSH acima da referência, a média de creatinina
foi 0,98 mg/dL e a de ureia foi 32 mg/dL. No sexo masculino,
o grupo com TSH dentro da normalidade teve média de creatinina de1,05 mg/dLe ureia de 27,89mg/dL. No grupo com
TSH aumentado, observamos média para creatinina de1,19
mg/dLe de ureia de 3,71mg/dL. Conclusão: A creatinina e a
ureia não são marcadores ideais de função renal, e a dosagem
de TSH isolada não faz diagnóstico de hipotireoidismo, dificultando a análise de alterações sistêmicas decorrentes dessa
doença, com base apenas na análise dessas variáveis.
Palavras-chave: creatinina; ureia; TSH.
PO120 ADEQUATE LEVOTHYROXINE DOSES FOR
THE TREATMENT OF SUBCLINICAL AND OVERT
HYPOTHYROIDISM NEWLY DISCOVERED DURING
PREGNANCY
Abalovich M1; Vázquez A1; Alcaraz G1; Calabrese C1; Kitaigrodsky A1;
Szuman G1; Astarita G1; Frydman M1; Gutiérrez S1
1
División Endocrinología Hospital Carlos G. Durand Background: Although under discussion, treatment of subclinical hypothyroidism (SCH) during pregnancy has been
recommended. Euthyroidism should be reached as soon as
possible but there are no precise indications about LT4 initial
dose. Objective: Determine the adequate LT4 dose to normalize TSH levels in patients with newly discovered SCH
and overt hypothyroidism (OH) during pregnancy and to
correlate them to basal TSH levels. Methods: Seventy-seven
patients with newly diagnosed hypothyroidism during pregnancy were retrospectively analyzed. Group 1: 64 with SCH
(TSH >2.5-10 mIU/L with normal FT4) and Group 2: 13
with OH (TSH >2.5 mIU/L with decreased FT4 or TSH >
10 mIU/L). SCH patients were subdivided: Group 1a: TSH
>2.5-4.2 mIU/L; Group 1b: TSH >4.21-10 mIU/L. LT4 dose
was considered adequate when TSH was ≤2.5 mIU/L in the
1st trimester or ≤3 mIU/L during the rest of the pregnancy.
Results: A significant difference (p<0.0001) in the adequate
LT4 dose (x±SD) was observed between Group 1: 87.33±24.60
mg/day, 1.31±0.36 mg/kg/day and Group 2: 147.08±29.83 mg/
day, 2.33±0.59 mg/kg/day, respectively. Group 1a required a
LT4 lower dose than Group 1b: 1.20±0.39 versus 1.42±0.31 mg/
kg/day, respectively (p<0.0014). With the initial calculated LT4
dose, a high percentage of women with SCH and OH quickly
achieved euthyroidism in the same trimester in which they
consulted. Conclusions: When SCH and OH are newly discovered during pregnancy, we recommend the use of the suggested mg/day and mg/kg/day LT4 doses, according to basal TSH
levels, to promptly achieve the euthyroid condition.
Keywords: pregnancy; hypothyroidism treatment; levothyroxine dose.
PO121 IMPACTO DEL EMBARAZO EN LA EVOLUCIÓN DEL
CARCINOMA DIFERENCIADO DE TIROIDES. NUESTRA
EXPERIENCIA A LO LARGO DE 22 AÑOS
Alcaraz G 1; Vázquez A2; Abalovich Marcos2; Calabrese C2; Frydman
M2; Gutiérrez S2; Chebel G3; Fadel AM4 1
División de Endocrinología, HOSPITAL DURAND; 2División de
Endocrinología, HOSPITAL DURAND; 3División de Endocrinología,
HOSPITAL DURAND; 4HOSPITAL DURAND Introducción: Es controvertida la influencia recíproca
entre cáncer de tiroides [CDT] y embarazo [E]. Objetivo:
a) Investigar el impacto del CDT sobre la evolución del E y
viceversa b) Establecer si existe > morbimortalidad neonatal
imputable a la enfermedad y/o tratamiento. Métodos: Se analizaron retrospectivamente 96E de 70 pacientes con carcinoma
69
Abstracts: Poster
papilar. Grupo 1 n=48 tiroidectomizadas y radioablacionadas
preembarazo cursaron 67E. Grupo 2 n=22 pacientes (29 E)
coexistentes con CDT. Se consideró libre de enfermedad (LE)
a pacientes con Tg/aTg e imágenes negativas. Resultados:
Grupo 1: 47/48 pacientes en estadio I. Dosis total de 131I preembarazo x=160 mCi (40-460), 31 E fueron concebidos a ≤12
meses de haber recibido 131I. 3/11 pacientes con enfermedad persistente preembarazo estaban LE a tiempo final [TF].
Partos: 46 a término, 10 abortos, 11 sin datos. Recién nacidos
[RN]: 43/46 normales, 2 malformados y 1 hipotiroideo. A TF:
133,76±79,34 m(x±DS), el 77,5% de las pacientes estaba LE.
Grupo 2: la PAF orientó el diagnóstico en 16/29 E. En 12/25 E
hubo crecimiento tumoral, 10 LE a TF. Partos: 20 a término, 3
pretérmino, 4 abortos, 2 sin datos. RN: 21/25 sanos, 1 presentó
reflujo urinario, 3 sin datos. Tiroidectomía: 20/22 post-parto,
1 intraembarazo, 1 rehusó cirugía. Estadio I: 20/21. El 78,95%
permaneció LE a TF:120,26±73,17 m. Observamos progresión de enfermedad intraembarazo en G2vsG1(p<0,0001).
Conclusiones: La gestación no afectó la evolución del CDT
tratado preembarazo. El 4,3% de malformaciones es similar al
referido en la población general y no parece ser imputable al
I131. En los casos de coexistencia de CDT y embarazo, un 48%
presentó crecimiento tumoral, aunque sin afectar la evolución
a TF, a pesar de diferir tiroidectomía al post-parto. El CDT no
influyó negativamente en la evolución del embarazo.
Palabras clave: evolución del cáncer; embarazo; progenie.
PO122 PLASMA SELENIUM LEVELS IN NEGATIVE THYROID
PEROXIDASE ANTIBODY PREGNANT WOMEM AND ITS
RELATION TO ABORTION AND PREMATURE DELIVERY
Mancini MM1; Teixeira PFS1; Silva NAO2; Coeli CM1; Vaisman M1
1
de Janeiro (UFRJ), Instituto Nacional do Câncier (INCA) Background: The presence of thyroid autoimmunity or
deficiency of some micronutrients, like selenium, exacerbate physiological changes in maternal thyroid function
and may result in maternal and fetal hypothyroidism with
higher incidence of spontaneous abortion or premature
birth. Objectives: 1. To determine selenium levels in pregnant women with negative thyroid peroxidase antibody
(antiTPO); 2. To evaluate the correlation between selenium
levels and thyroid-stimulating hormone (TSH) and free
thyroxine (FT4) levels in this population and 3. To study
the association between selenium levels and pregnancy
unwanted outcomes, such as abortion and premature delivery. Methods: This is a longitudinal study that included,
sequentially, 125 pregnant women attending a prenatal clinic in the state of Rio de Janeiro (Brazil), between the 1st
and 14th weeks of pregnancy, without thyroid disease. We
obtained serum measurements of TSH, FT4, antiTPO and
selenium at enrollment in the study and observed outcomes during late gestation. Results: Low serum levels of
selenium were observed in 48% of de patients. There was a
significant correlation between selenium and FT4 levels (rs
=0.27; p=0.002), but not with TSH (rs=-0.13; p=0.163). No
significant correlation was demonstrated between selenium
levels and unfavorable pregnant outcomes. Conclusions:
Low serum selenium in a group of pregnant women without
thyroid disease did not increase the prevalence of abortion
or premature delivery in this population.
Keywords: thyroid; selenium; pregnancy.
70
PO123 PERFIL TIROIDEO EN UNA POBLACIÓN DE
EMBARAZADAS SANAS DE LA CIUDAD AUTÓNOMA DE
BUENOS AIRES
Rodríguez MF1; Silva Croome MC1; Lutzky C2; Ilera V3; Zunino A3; Glikman P3; Serrano López D3; Scalise C3; Gauna A1; 1
Hospital General de Agudos J.M. Ramos Mejía; 2Lutzky C; 3Hospital General
de Agudos J.M. Ramos Mejía
Antecedentes: La disfunción tiroidea en el embarazo ocasiona
complicaciones obstétricas y fetales. Para diagnosticarla, en
ausencia de valores propios, hay que referirse a los valores de
las Guías de ATA para embarazadas. Objetivos: Comparar
niveles de las hormonas tiroideas y TSH en diferentes trimestres y sus correlaciones. Evaluar concordancia en diagnóstico
de hipotiroidismo subclínico utilizando valores de las guías
de ATA vs los resultados de este estudio. Métodos: Estudio
prospectivo entre junio y octubre de 2012, observacional en 224 embarazadas mayores de 16 años, residentes en
CABA (área yodosuficiente). Excluimos tiroideopatía conocida y/o TPOAb+ (n=32). Medimos TSH, T4, T4L, T3, T3L
(QLIA/IMMULITE2000) en 1°trimestre (n=69); 2°trimestre
(n=85); 3°trimestre (n=38). Estadística: Regresión lineal,
Test de ANOVA paramétrico y no paramétrico según variables. Resultados: TSH(mUI/L) Mediana/P5/P95: 1°trim:
1,0/0,46/3,0; 2°trim:1,6/0,5/4,0; 3°trim: 1,6/0,9/3,1 (1°< vs 2°
y 3°trim, p<0,001). T4(ug/dL) media/SD: 1°trim: 10,5/1,6;
2°trim: 10,9/1,6; 3°trim:10,4/1,6 (1° vs 2° vs 3°: NS).T4L(ng/
dL) media/SD: 1°trim: 1,01/0,12; 2°trim: 0,92/0,11; 3°trim:
0,88/0,14 (1°> vs 2° y 3°trim p<0,001). T3(ng/dL) media/
SD: 1°trim:155/35; 2°trim:192/45; 3°trim:194/52 (1°< vs
2°,p). Conclusiones: En el primer trimestre, TSH, T3 y T3L
fueron menores y T4L mayor que en el segundo y en el tercero. T4 no varió. El número de gestantes con diagnóstico de
Hipotiroidismo subclínico en el primero y en el segundo trimestres hubiera sido sobreestimado, considerando los valores
de las guías de ATA.
Palabras clave: perfil tiroideo; embarazo; hipotiroidismo.
Thyroid Regulation
PO124 IDENTIFICAÇÃO DA VIA DE DEGRADAÇÃO DO
COTRANSPORTADOR SÓDIO-IODETO INDUZIDA PELA
CINASE ATIVADA POR AMP
Introdução: Recentemente, demonstramos que a cinase
ativada por AMP (AMPK) é expressa na tireoide de ratos e
na linhagem PCCL3 e que sua ativação inibe a captação do
iodeto devido à queda dos níveis proteicos totais e de RNAm
do cotransportador Na+/I- (NIS) em 24 h. Visto que a meiavida do NIS é longa (3-5 dias) e que a redução no conteúdo
proteico do NIS mediado pela AMPK acontece em 24 h, é
possível que a ativação da AMPK estimule a degradação
proteica do NIS. Objetivo: Avaliar o mecanismo de degradação do NIS mediada pela AMPK. Metodologia: Células
PCCL3 foram tratadas com o ativador farmacológico da
AMPK, AICAR (A) e/ou inibidor específico da via lisosomal
de degradação proteica, Bafilomicina A1 (BA1), ou ambos
por 24 h. As células também foram submetidas à privação de
TSH por 24 h na presença ou ausência de BA1. Resultados:
Tanto o tratamento com AICAR quanto a privação de TSH
por 24 h inibiram significativamente a captação de iodeto nas
Abstracts: Poster
células PCCL3 em relação ao controle e, interessantemente,
essa inibição e ambas condições foi completamente revertida
na presença da BA. O AICAR promoveu queda de cerca de
40% dos níveis proteicos de NIS assim como a privação de
TSH por 24 h, e ambos os efeitos foram revertidos pelo tratamento com BA1. Conclusão: A captação de iodeto pelas células PCCL3 depende da velocidade de degradação da proteína
NIS que é ativada tanto pela AMPK quanto após privação de
TSH, através de um processo de degradação dependente da
via lisossomal.
Palavras-chave: AMPK; NIS; PCCL3.
PO125 TREATMENT WITH FLAVONOID RUTIN INCREASES
THYROID RADIOIODIDE UPTAKE
Gonçalves CFL1; Santos MCS1; Carvalho DP1; Ferreira ACF1
1
Janeiro (IBCCF/UFRJ)
Flavonoids are polyhydroxyphenolic compounds found in
vegetables present in human diet. Studies have suggested that
these compounds could interfere with thyroid function causing goiter and hypothyroidism. Rutin (3‘.4‘.5.7-tetrahydroxyflavone-3-rutinoside) is a highly consumed flavonoid,
found in foods, such as onions, apples and teas, and also in
multivitamin compounds. The aim of the present study was
to evaluate the effects of the in vivo treatment with rutin on
thyroid gland, evaluating both activity of proteins involved in
the synthesis and metabolism of thyroid hormones, besides
the effect on thyroid axis. Thus, rats received rutin (20 mg/
kg body weight) or vehicle (propyleneglycol) for 5 days, subcutaneously. The treatment with rutin significantly increased
radioiodide uptake and thyroid mRNA levels of Na+/I– symporter, thyroperoxidase, type 1 deiodinase and thyrotropin
receptor. However, thyroid hormones serum concentrations
were decreased without changes in serum thyrotropin (TSH).
In vitro, rutin was able to potently inhibit TPO iodide-oxidation activity, with 50% activity inhibition in the concentration
of 3.4 mM. But this inhibitory effect of rutin on TPO does
not appear to be due to its antioxidant action. Treatment with
rutin significantly increased hypothalamus, pituitary and
brown adipose tissue type 2 deiodinase activities and decreased liver type 1 deiodinase activity. We conclude that the in
vivo treatment with rutin is able to affect thyroid hormone
synthesis and metabolism, reducing thyroid hormone serum
concentration. Our results suggest that rutin could be used
as adjuvant in radioiodine therapy, in future. However, more
studies must be done to better understand the flavonoid utilization.
Keywords: Na+/I- symporter; rutin; thyroid.
PO126 INFLUÊNCIA DA DENSIDADE CELULAR SOBRE A
FUNÇÃO DO COTRANSPORTADOR NA+/I- EM CULTURA DE
CÉLULAS PCCL-3
Lima LP1; Cortez R1; Ferreira ACF1; Carvalho DP1
1
Laboratório de Fisiologia Endócrina Doris Rosenthal/Instituto de Biofísica
Carlos Chagas Filho/Universidade Federal do Rio de Janeiro (ICB/UFRJ) Introdução: Estudos prévios do nosso laboratório demonstram que quanto maior o bócio, mais intensa é a regulação
negativa do cotransportador sódio-iodeto (NIS) na presença
de retomada da organificação do iodo in vivo em ratos Wistar.
Objetivo: Estudar a atividade e expressão do NIS em diferentes graus de confluência celular em cultura da linhagem
de tireócitos murinos PCCL-3. Métodos: Células PCCL-3
foram cultivadas na presença de TSH e insulina, 5% de SFB
e em confluências celulares de 50%, 70% e 100%. Analisamos
a captação de iodeto, a expressão das proteínas NIS e receptor de TSH através de Western blot e do RNAm do NIS através de real time PCR. Todos os resultados foram expressos
como relativo a 50% de confluência. Resultados: Na confluência mais alta, observamos redução da captação de iodeto
(50%=1,05±0,10; 70%=0,87±0,05*; 100%=0,63±0,06***, *p<
0,05 versus 100%; ***p < 0,001 versus 50%) e diminuição da
expressão da proteína do NIS (50%=1,00; 70%=0,58±0,039;
100%=0,24±0,10). Não observamos qualquer variação
significativa do RNAm do NIS em função das diferentes
densidades celulares (50%=1,00±0,028; 70%=0,98±0,063;
100%=0,93±0,059) ou dos níveis proteicos do receptor de
TSH (50%=1,00±0,20; 70%=0,85±0,36; 100%=0,71±0,51).
Conclusões: O presente estudo mostra que a função e a
expressão proteica do NIS são reguladas negativamente em
densidades mais altas de tireócitos. Nossos dados sugerem
ainda que esse efeito pode ser resultante de uma regulação
pós-transcricional não mediada por TSH, já que não houve
alteração da expressão do seu receptor. Portanto, a celularidade parece afetar de forma importante a função do cotransportador sódio-iodeto.
Palavras-chave: NIS; densidade; rTSH.
PO127 IDENTIFICATION OF G-PROTEIN COUPLED
RECEPTOR 30 (GPR30/GPER) IN HUMAN NORMAL THYROID
CELLS
Santin AP1; Loureiro SO1; Pessoa-Pureur R1; Brum IS1; Furlanetto TW1
1
Universidade Federal do Rio Grande do Sul (UFRGS) Thyroid nodules and differentiated thyroid cancer are more
common in women, and the incidence of the last has been
increasing, which could be due to estrogen effects in thyroid
cells. Estrogen responses are typically mediated through classical estrogen receptors, a and b-isoforms, which have been
described in normal and abnormal human thyroid tissue,
although effects mediated through G protein estrogen receptor 1 (GPR30/GPER), described in some thyroid cancer cell
lines, could be responsible for regulation of growth in normal
cells. In this study, GPR30 gene and protein expression are
described in normal human thyroid cells in primary culture
and is possibly localized in plasma membrane and perinuclear region by immunocytochemistry. Further studies are
needed to determine the functionality of these receptors in
the thyroid as well as its role in normal and abnormal conditions.
Keywords: thyroid; GPER; physiology.
Thyroid Hormone Action
PO128 THYROID HORMONES (THS) REGULATE THE
EXPRESSION OF MRNA OF PROTEINS RESPONSIBLE FOR
IRON HOMEOSTASIS IN LIVER OF RATS
Sena-Souza J1; Duarte JS2; Maciel RMB1; Giannocco G2 1
Universidade Federal de São Paulo (UNIFESP); 2Faculdade de Medicina do
ABC (FM/ABC) Background: THs stimulate basal metabolic rate that requires
an adequate oxygen transport. The human body needs iron
for oxygen transport and tightly regulate iron absorption and
recycling through specialized proteins like ferritin, transfer-
71
Abstracts: Poster
rin, ferroportin and hepcidin. Objectives: Evaluate if the variation of thyroid status can modulate the gene expression of iron
homeostasis proteins. Methods: Male Wistar rats (200-250 g)
were submitted to surgical thyroidectomy (Tx) and subsequent
treatment with methimazole (0.01%) in the drinking water for
20 days. Partial Tx to induce subclinical hypothyroidism (HS)
was performed. Control group was submitted to a surgical procedure without ablation of thyroid gland (C). Here we treated
Tx with 5 X and 10 X T35 days and HS (1X T4). After decapitation the duodenum and liver were excised, total mRNA was
extracted by Trizol® and gene expression evaluated by Real
Time PCR. Results: In HS animals liver ferritin was increased
(p<0.0001) compared to control, TX, 5X T3, 10X T3; ferroportin was increased in TX (p=0.0207) compared to control;
hepcidin was increased (p<0.0001) in TX animal compared to
control, 5X T3 and 10X T3, and HS was decreased (p<0.05)
compared to TX, control, 5X T3, 10X T3; HS+T4 was decreased (p<0.0001) compared to TX. Transferrin receptor in TX
was increased (p=0.0389) compared to 10X T3, and transferrin
was increased (p=0.0188) in TX compared to 5X T3. In duodenum, HT has not changed mRNA expression. Conclusions:
HTs play a role in gene expression of iron homeostasis proteins
in a tissue specific way.
Keywords: thyroid hormone; iron homeostasis; gene expression.
PO129 ANTI-TUMOR IMMUNE RESPONSE MODULATION BY
THYROID STATUS INFLUENCES THE DISSEMINATION OF A
MURINE T CELL LYMPHOMA
Sterle HA1; Valli E1; Paulazo MA1; Colombo L2; Barreiro Arcos ML1;
Cremaschi GA3
1
Instituto de Investigaciones Biomédicas/Consejo Nacional de Investigaciones
Científicas y Técnicas/Pontificia Universidad Católica Argentina (UCA/
CONICET); 2Instituto de Oncología AH Roffo; 3Consejo Nacional de
Investigaciones Científicas y Técnicas/Pontificia Universidad Católica
Argentina (UCA/CONICET); Facultad de Farmacia y Bioquímica/
Universidad de Buenos Aires (UBA) Background: We have previously shown that thyroid hormones (THs) are able to regulate the immune system, but their
role in antitumor responses is not well known. Objective:
Our aim was to evaluate THs involvement in the development of a T cell lymphoma, with the focus on their effects
on the immune system response. Methods: We developed
murine models of hyper- and hypothyroidism in C57BL/Hep
mice by oral administration of T4 or of the anti-thyroid agent
propylthiouracil, respectively. These mice were further inoculated subcutanously with the EL-4 T lymphoma cell line to
obtain solid tumors and intravenously to evaluate tumor dissemination. Results: Hyperthyroid mice showed a higher tumor
growth rate and higher tumor volume than eu and hypothyroid
ones, which was related with the modulation of genes involved in the cell cycle regulation. We additionally observed that
hypothyroid and hyperthyroid mice developed, respectively,
a higher and lower number of metastases than controls. We
found that hyperthyroid animals showed an increased number of NK and CD8+ cells accompanied with an increased NK
cytotoxic activity, while hypothyroid animals showed a reduced
tumour-specific T lymphocyte cytotoxic activity. Conclusions:
These results suggest that thyroid status can directly modulate
tumor development through the regulation of tumor growth
and could regulate tumor dissemination through the modulation of the anti-tumor immune response.
Keywords: T cell lymphoma; immune response; cell cycle.
72
PO130 ASSOCIAÇÃO DE T3 E E2 ATIVA C-FOS,
RESPONSÁVEIS PELA ATIVAÇÃO OSTEOCLÁSTICA EM
OSTEOBLASTOS HUMANOS DERIVADOS DE TECIDO
ADIPOSO
PPS1; Olimpio RMC1; Sibio MT1; Oliveira M1; Ferreira T1; Conde S1;
Nogueira CR1
1
Faculdade de Medicina de Botucatu/Universidade Estadual Paulista (UNESP) Introdução: Hormônios da tireoide e estrógeno influenciam diretamente no metabolismo ósseo. A interação entre
RANK e RANKL é a via mais conhecida na diferenciação
e ativação osteoclástica. O RANK promove a maturação
osteoclástica por meio de genes específicos, incluindo o
fator de transcrição c-Fos. Pacientes e métodos: O tecido
adiposo foi obtido por abdominoplastia de 3 pacientes. As
células tronco mesenquimais (CTMs) foram extraídas por
dissociação enzimática. Após sua caracterização de CTMs
e osteoblastos, os tratamentos hormonais com T3 (tri-iodotironina) e E2 (estrógeno) foram iniciados: controle (E2
+ T3 fisiológicos), T3 (infrafisiológico + E2 fisiológico), T3
(suprafisiológico + E2 fisiológico), T3 (infrafisiológico +
E2 infrafisiológico), T3 (suprafisiológico + E2 infrafisiológico), T3 (fisiológico + E2 infrafisiológico). Para verificar
se a expressão gênica do RANKL, OPG (osteoprotegerina)
e c-Fos foram realizados exames de PCR em tempo real.
A análise estatística foi realizada pelo teste de ANOVA,
complementada pelo teste de Bonferroni. Resultados: A
expressão gênica de RANKL nos diversos tratamentos não
mostrou diferença quando comparado ao grupo controle.
Porém no grupo T3 (infrafisiológico) + E2 (infrafisiológico), c-Fos e OPG apresentaram aumentados em relação
ao grupo controle. Conclusão: Embora os genes analisados
tenham sido ativados pela adição hormonal de T3 e E2,
RANKL não apresentou aumentada devido ao aumento da
expressão de OPG que foi estatisticamente significante em
relação ao grupo controle. Além disso, houve aumento da
expressão gênica de c-Fos, e isso pode ser outra via para
ativação osteoclástica independente de RANKL. Apoio
financeiro: FAPESP.
Palavras-chave: RNAKL; osteoblasto; hormônio tireoidiano.
PO131 THYROID HORMONE STATUS INTERFERES WITH
ESTROGEN TARGET GENE EXPRESSION IN BREAST
CANCER SAMPLES OF MENOPAUSAL WOMEN
Conde SJ1; Luvizotto RAM1; Síbio MT1; Nogueira CR1
(FMB/UNESP)
1
Correlations between thyroid disorders and breast cancer
(BrC) have prompted questions about the effect of thyroid
hormone and its association with estrogen on breast tumor
genesis and progression. In this study, we investigated
thyroid hormone levels in menopausal BrC patients and
verified the action of triiodothyronine on genes regulated
by estrogen and by triiodothyronine itself in BrC tissues.
We selected 15 postmenopausal BrC patients and a control
group of 18 postmenopausal women without BrC. We measured serum thyroid peroxidase antibody, thyroid-stimulating hormone, free thyroxine and estradiol, before and after
surgery and used immunohistochemistry to examine estrogen and progesterone receptors. BrC primary tissue cultures
received the following treatments: ethanol, triiodothyronine, triiodothyronine+tamoxifen, tamoxifen, estrogen or
Abstracts: Poster
estrogen+tamoxifen. Genes regulated by estrogen (TGFA,
TGFB1 and PGR) and by triiodothyronine (TNFRSF9,
BMP-6 and THRA) in vitro were evaluated in each patient.
Three BrC patients presented with clinical hyperthyroidism. Thyroxine levels of BrC patients were statistically
higher than controls (1.78±0.20 versus 0.95±0.16 ng/dL).
TGFA and TGFB1 were upregulated and downregulated,
respectively, after estrogen and triiodothyronine treatment.
Triiodothyronine treatment increased PGR expression;
however tamoxifen did not block triiodothyronine action
on PGR expression. Tamoxifen, alone or associated with
triiodothyronine, modulated gene expression of TNFRSF9,
BMP-6 and THRA, similar to triiodothyronine treatment,
showing that tamoxifen can interfere with gene expression
modulated by triiodothyronine. Our results reinforce that
the thyroid hormone status of BrC patients can influence
estrogen-controlled processes, even after tamoxifen intervention and/or in the absence of circulating estrogen postmenopause. Thus, our work highlights the importance of
thyroid hormone status evaluation.
Keywords: thyroid hormone; estrogen; tamoxifen.
PO132 ISOCITRATE DEHYDROGENASE 1 (IDH1) MUTATIONS
ARE PRESENT IN A HIGH PREVALENCE IN THYROID
CARCINOMAS AND ARE ASSOCIATED WITH SPECIFIC
HISTOLOGICAL SUBTYPES AND LARGER TUMORS
Moraes LS1; Carvalheira GMG1; Nozima BHN1; Bastos AU1; Besson
PS1; Evangelinellis MM1; Hermely JP1; Cerutti JM1 1
Universidade Estadual de São Paulo (UNIFESP)
Background: The hallmarks of cancer were recently revisited. The authors proposed that metabolic pathway is 1 of
the 4 new hallmarks. We recently reported that Isocitrate
Dehydrogenase 1 gene (IDH1), a key enzyme in the metabolism of carbohydrates, is mutated in thyroid carcinomas.
Recently, others authors showed that these variants results
in a decreased of wild-type function. Objectives: To investigate the prevalence of IDH1 and IDH2 variants in a large
series of thyroid tumors, its association with clinic-pathological features and co-occurrence with genetic alterations in
MAPK and PI3K pathways. Methods: A total of 236 samples
were screened for mutations in IDH1, BRAF, HRAS, NRAS,
PIK3CA, IDH2 and the presence of RET/PTC 1, 2 and 3 rearrangements. Results: We detect the presence of IDH1 nonsynonymous variants in 12% of malignant thyroid lesions. No
variants were found in benign lesions and in normal thyroid
tissue. These variants were mainly found in follicular thyroid
carcinoma and follicular variant of papillary thyroid carcinoma
when compared with classical variant (p<0.05), showing a
trend of association between a specific variant and histological
subtype. Although most IDH1 variants (64%) occurred alone,
we here described co-occurring MAPK pathway and IDH1
mutations. Finally, IDH1 positive tumors were larger than
IDH1 negatives tumors (p<0.05). Conclusions: IDH1 variants
occur in thyroid carcinomas associated with specific histological subtypes and tumor size. Different that previously reported,
IDH1 mutations co-occur with mutations in genes encoding
protein along MAPK pathway. The specificity of these variants
may help diagnosis and treatment of thyroid carcinomas.
Keywords: IDH; MAPK; PI3K.
PO133 PUNCIÓN INTRAQUIRÚRGICA DE TIROIDES PARA
LA DETECCIÓN DE MUTACIÓN DEL ONCOGEN BRAF
Ilera V1; Silva Croome MC1; Dourisboure R1; Olstein G1; Colobraro A1;
Zunino A1; Lowenstein A1; Reyes A1; Gauna A1
1
Hospital Ramos Mejía Introducción: La mutación del oncogen BRAF puede tener
valor pronóstico en carcinoma papilar de tiroides (CPT) y
utilidad diagnóstica en punciones aspirativas con aguja fina
(PAAF) indeterminadas. El tamaño de muestra para el estudio
puede ser una limitante en microcarcinomas. No hay reportes
realizados en punción intraquirúrgica (PAAFCx). Objetivos:
Determinar la utilidad de la PAAFCx en la determinación
de la mutación del BRAF. Métodos: Estudio prospectivo en
pacientes tiroidectomizados. Se realizó PAAFCx “in vivo” al
tejido nodular y adyacente normal. Se comparó con muestras
histológicas de 0,5 cm obtenidas en fresco de los mismos sitios
y pacientes. De todas las muestras se extrajo ADN, se amplificó según técnica ARMS (Amplification Refractory Mutation
System) PCR y se leyó el patrón de bandas en gel de agarosa.
Se determinó sensibilidad (S), especificidad (E), valor predictivo positivo (VPP), valor predictivo negativo (VPN) y exactitud diagnóstica (ED) de PAAFCx para detectar la mutación
del BRAF. Resultados: 67 análisis del BRAF en 18 pacientes:
8 operados por CPT y 10 por hiperplasia nodular coloide. Se
obtuvieron 34 muestras histológicas y 33 PAAFcx. En 31/32
muestras hubo concordancia para mutación del BRAF entre
citología e histología (96,87%). PAAFCx tuvo S 83,3%, E
100%, VPP 100%, VPN 96,3% y ED 96,87%. Conclusiones:
La detección de mutación del BRAF por PAAFCx tuvo una
concordancia >90% con la realizada a partir de material histológico. Consideramos: a) PAAFCx puede permitir la obtención de material en microcarcinomas sin detrimento del estudio histológico; b) estos resultados avalan la realización del
estudio en PAAF pre-quirúrgica.
Palabras clave: mutación BRAF; punción intraquirúrgica de
tiroides; carcinoma papilar de tiroides.
PO134 INCREASED EXPRESSION OF MATRIX
METALLOPROTEINASE-9 AND THEIR INHIBITORS
IN PAPILLARY THYROID CARCINOMA: CLINICAL
IMPLICATIONS
Pinto Ribeiro RV1; Romitti M1; Ceolin L1; Ferreira CV1; Wajner SM1;
Meurer L1; Brazil BA1; Maia AL1
1
Universidade Federal do Rio Grande do Sul (UFRGS) The matrix metalloproteinases (MMPs) constitute a group of
enzymes that degrade the extracellular matrix and basement
membrane components. Studies have demonstrated overexpression of these enzymes and their tissue inhibitors (TIMP-1
and TIMP-2) in several carcinomas, suggesting that these
molecules might be implicated on the mechanisms of angiogenesis involved in tumor progression. Objective: To evaluate the
expression of MMP-9 and their inhibitors in papillary thyroid
carcinoma (PTC) samples and correlate with clinical parameters. Methods: PTC samples and surrounding tissue paraffinembedded blocks were submitted to immunohistochemical analyzes using specific antibodies. The expression levels
were evaluated by Image-Pro Plus software and expressed as
Integrated Optical Density (IOD). Results: Sixty-three patients
were enrolled (aged 45.3±14.9 years; 82.6% female). Local or
distant metastasis were present in 46.8% and 9.7% of cases at
diagnosis, respectively. As compared with surrounding thyroid
73
Abstracts: Poster
tissue, increased expression of MMP-9 [(31.8 (22.6-35.5) versus
133.4 (80.1-181.5); p<0.001], TIMP-1 [(148.2 (96.8-231.1) versus 20.6 (19.5-29.4); p<0.001)] and TIMP-2 [(86.8 (30.4-327.8)
versus 8.03 (2.4-10.4); p<0.001)] were observed in PTC samples. Higher TIMP-1 levels correlated with younger age (r=0.32;
p=0.001) and small tumors (<1.0 cm; p=0.013) at diagnosis.
Increased levels of TIMP-1 (p=0.027) and TIMP-2 (p=0.04)
were also associated with intra-thyroidal disease. MMP9 levels
were positively correlated with VEGF levels (r=0.73; p<0.001)
but, unexpectedly, no association was observed between
MMP-9 levels and metastatic disease (p>0.05). Conclusion:
Taken together, these results indicate a role for MMP and their
inhibitors in PTC pathogenesis and might suggest a potential
role for these molecules as markers of tumor behavior.
Keywords: papillary thyroid carcinoma; matrix metalloproteinases; TIMP-1.
Thyroid Regulation
PO135 THYROTROPIN (TSH) REFERENCE RANGE IN
ELDERLY PEOPLE: A POPULATION BASED STUDY IN RIO
DE JANEIRO
Fontes R1; Coeli CR2; Aguiar F2; Vaisman M2
Diagnósticos da América SA; 2Universidade Federal do Rio de Janeiro 1
Background: Some studies show a tendency to increase thyrotropin (TSH) levels with advancing age. Surks et al observed
that while the percentage of individuals with TSH>4.5 mUI/
mL was 2.5% in young people; it rose up to 12% among those
>80 years-old. Bremner et al. found that TSH levels gradually
increased during a 13-year period, with greater increase in
those >60 years-old. Objectives: To describe changes in TSH
by age groups in a cohort of elderly individuals, in comparison with young ones and determine the reference range to
each age group. Methods: Cross-sectional analysis of 1195
individuals (50% women), mean age 62.2±18 years (20-100),
without goiter, no previous personal or family history of
thyroid disease and negative thyroid antibodies. Results:
Women had higher mean TSH (2.42±1.64 versus 2.2±1.39
mUI/mL; p=0.03) and lower mean Free T4 (FT4). TSH
levels increased significantly (p<0.001; 20-49=1.62±1.14,
50-59=1.83±1.13, 60-69=1.90±1.27, 70-79=2.06±1.04, ≥ 80
years-old=2.21 +- 1.46 mUI/mL), whereas FT4 decreased significantly, with aging. Conclusions: Our study shows a gradual increase in TSH levels in healthy aging and establishes
the normal medians for each age group in Rio de Janeiro. References:
1. Surks et al. JCEM. 2007; 92: 4575-82. 2. Bremner et al. JCEM. 2012; 97: 1554-1562.
Keywords: TSH; aging; thyroid.
PO136 PERFIL DE POPULAÇÃO RASTREADA PARA
DOENÇAS TIREOIDIANAS DURANTE CAMPANHA “EXAMINE
SUA TIREOIDE”
Guedes LSM1; Brasileiro ES1; Arruda CCC1; Silva KF1; Torres FF1;
Leite DSA1; Cruz NA1; Bezerra CSM1; Sampaio RAAF1; Filho PCM1;
Forti AC1; Façanha CFS2
1
Universidade Federal do Ceará (UFC); 2Sociedade Brasileira de
Endocrinologia e Metabologia/Regional Ceará (SBEM/CE) Introdução: A Sociedade Brasileira de Endocrinologia e
Metabologia (SBEM) e a Sociedade Brasileira de Cirurgia de
Cabeça e Pescoço (SBCCP) realizaram, no dia 26 de maio de
74
2012, a campanha “Examine Sua Tireoide em praças e shopping centers de Fortaleza”. Objetivos: Esclarecer sobre as
doenças da tireoide e rastreá-las na população de risco, além
de facilitar o acesso ao especialista. Métodos: Foram avaliados 546 participantes, através da palpação da tireoide, por
17 endocrinologistas e 53 estudantes, e foram aplicados 493
questionários que abordavam os principais sinais e sintomas
das afecções tireoidianas. Foram solicitados exames de TSH
e ultrassonografia (USG) de acordo com o risco observado.
Posteriormente, houve a reavaliação dos pacientes. Uma
intensa campanha de mídia foi realizada na semana anterior
à campanha. Na análise estatística, foi utilizado o programa
Epi Info, versão 3.5.3. Resultados: A população atingida
pela campanha mostrou o seguinte perfil: idade média: 44,5
anos; 79,5% do sexo feminino; 39,5% com história familiar
de doença tireoidiana. O acesso à campanha deu-se por
mídia televisionada em 48%. Os sintomas mais frequentemente referidos foram: cansaço (53,8%), queda de cabelos
(43,8%), unhas fracas (40,1%), pele seca (39,9%), aumento do
peso (34,4%), sonolência (32%) e bócio tireoidiano (22,4%).
Foram solicitados TSH em 33,3% e USG de tireoide em
19,2%. Conclusão: Foi demonstrada elevada prevalência de
manifestações clínicas relacionadas aos distúrbios tireoidianos entre os entrevistados. A população feminina com idade
média de 44,5 anos revelou-se como o grupo mais consciente
da necessidade de procurar atendimento médico, porém com
difícil acesso, no nosso meio, ao especialista, demonstrando a
importância da realização da campanha.
Palavras-chave: rastreamento; diagnóstico precoce; medicina preventiva.
PO137 TOMOGRAFÍA POR EMISIÓN DE POSITRONES Y EL
DILEMA DEL MEDIASTINO
Califano I1; Reyes A2; Lowenstein A2; Coduti M1; Zarlenga C1; Salariato O1; Saco P1; Califano L1 1
Instituto AH Roffo; 2Hospital Ramos Mejía Introducción: La tomografía por emisión de positrones
(PET) está indicada en el cáncer diferenciado de tiroides
(CDT) con Tiroglobulina (Tg) elevada y estudios de localización negativos. Sus limitaciones son su alto costo y las captaciones inespecíficas (falsos positivos, FP). Las recurrencias
mediastinales son habituales en CDT, aunque en esta localización es frecuente hallar FP. Objetivos: 1) Evaluar prevalencia de captaciones mediastinales en PET; 2) Determinar
cuántas fueron FP. Materiales y Métodos: Se evaluaron,
retrospectivamente, 35 pacientes con CDT estudiados con
PET. Se determinó presencia de captación mediastinal de
FDG, correlacionado con hallazgos en otros estudios de imágenes y quirúrgicos. Resultados: En 11 pacientes (31%) se
detectaron focos mediastinales. Siete fueron verdaderos positivos (VP, 3 confirmados histológicamente; 4 con enfermedad
cervicomediastínica). Los 4 restantes fueron FP: 3 operados
(diagnósticos: fibrosis, timo, adenopatías inespecíficas, tejido
adiposo); el cuarto evolucionó con remisión bioquímica y
estructural. Los niveles de Tg fueron 180 ng/mL (VP) vs 17
(FP) (p ns). Los valores de SUVm fueron 8,2 (VP) vs 3,8 (FP)
(p ns). Ningún FP presentó SUV m > 4,5. Conclusiones: 1)
Se observaron captaciones mediastinales en un tercio de los
PET, correspondiendo un 36% a FP. 2) No hubo correlación
Abstracts: Poster
entre niveles de Tg y hallazgo de metástasis mediastinales. 3)
Todos los focos con SUVm > 4,5 fueron metastásicos; valores inferiores se encontraron en FP y en metástasis. 4) Deben
evaluarse individualmente los antecedentes, clínica y estudios, para evitar cirugías innecesarias en pacientes con captaciones inespecíficas.
Palabras clave: Thyroid cancer; PET; mediastinum.
PO138 MICROCARCINOMAS DE MUY BAJO RIESGO NO
TRATADOS CON RADIOYODO
Utreras C1; Díaz RE2; Ramos C3; Millar ES2; Véliz J2; Wohllk N4 1
Hospital del Salvador, Santiago de Chile. IEMA, Universidad de Chile;
2
Sección de Endocrinología, Hospital del Salvador, Universidad de
Chile; 3Sección de Endocrinología, Hospital del Salvador; 4Sección de
Endocrinología, Hospital del Salvador, Universidad de Chile, IEMA
Introducción: La incidencia de los microcarcinomas papilares (MPC) ha aumentado + 400% en las últimas décadas.
Según los últimos consensos, el 131I no estaría recomendado
en los MPC de bajo riesgo. Desde hace 10 años, en nuestro
servicio los MCP de muy bajo riesgo (MCPMBR) se han definido como variedad clásica: unifocal; sin invasión vascular y
sin compromiso capsular y ganglionar, no han sido tratados
con 131I. Objetivo: Conocer la evolución de los MCPMBR
tratados con cirugía exclusiva. Material y Método: Se revisó
la base de datos de los pacientes con cáncer de tiroides. De
429 pacientes, 52 (12%) cumplieron con los criterios de
MCPMBR. Resultados: 87% mujeres; edad promedio 48 años
(24-70). TSH promedio 4,3 uUI/mL (rango 0.01-75). Se realizó tiroidectomía total (TT) o subtotal en 69% y, en el resto,
lobectomía o lobectomía + istmectomía. El tamaño promedio fue de 4,6 mm (rango 1-10). La biopsia reveló tiroiditis
crónica en 8%. El seguimiento se realizó cada 6 meses con
tiroglobulina (Tg), anticuerpos Tg, bajo supresión con LT4
y ecografía cada 6 meses, en los primeros dos años, y luego
anual. El seguimiento promedio fue de 5,7 años (1-25). Solo
una paciente (con TT) presentó elevación persistente de Tg
con doblaje de 2.6 años. No hubo evidencia imagenológica de
metástasis cervicales o a distancia, por lo que se mantuvo en
observación. Ningún paciente requirió nueva cirugía o tratamiento con radioyodo. Conclusiones: Nuestros resultados
son similares a los publicados en la literatura internacional, lo
que confirma que los MCTMBR tienen una muy baja probabilidad de recidivar.
Palabras clave: papillary thyroid cancer; microcarcinoma;
radioiodine.
PO139 ASSOCIAÇÃO ENTRE TIREOIDITE DE HASHIMOTO E
CÂNCER DA TIREOIDE: ANÁLISE DE 49 CASOS
Alcântara-Jones DM1; Lavinas-Jones JM1; Daltro R1; Pitangueira AC1;
Alcântara FT1; Melo AFO1; Cardoso C1; Cruz VFG1 1
Hospital São Rafael/Universidade Federal da Bahia (HSR/UFBA) Objetivos: Busca-se avaliar a associação entre tireoidite de
Hashimoto (TH) e carcinoma papilífero da tireoide (CP),
correlacionando aspectos comuns entre eles. Material e
métodos: Estudaram-se portadores de bócios nodulares,
por punção aspirativa por agulha fina (PAAF), guiada pela
ultrassonografia (USG), para avaliar o percentual que albergavam malignidade e tireoidite. Para TH, consideraram-se
aspectos característicos da citopatologia e, para associação
entre as patologias, os aspectos histopatológicos clássicos.
Resultados: Foram avaliados por PAAF, no HSR, 1055 portadores de bócios nodulares (909 do sexo feminino e 146 do
sexo masculino); 173 (16,4%) tinham quadro citopatológico
de tireoidite. Dos 49 operados, 5 (10,2%) tiveram diagnóstico
de TH na histopatologia, 33 (67,4%) revelaram CP, dos quais
9 (27,3%) tinham concomitantemente quadro histopatológico
de TH. Nos 32 casos de nódulos benignos, 5 (31,3%) exibiam
também TH e 2 outras patologias associadas. Nos grupos TH/
CP/CP+TH, a proporção de acometimento do gênero feminino foi, respectivamente: 100%/91,6%/77,8%. A distribuição
da média da idade (anos) nos 3 grupos foi: 41,5/43,3/48,5.
Não houve associação entre as 2 patologias neste estudo, em
que a TH estava presente em 31,1% dos benignos e em 27,3%
dos malignos. Discussão: A associação das patologias tem
respaldo em estudos com marcadores moleculares. Em outras
séries, há maior proporção de nódulos benignos, enquanto
neste estudo, 67,4% eram nódulos malignos. Conclusões:
Não houve associação entre TH e CP, mas a possibilidade de
malignidade em TH deve ser lembrada em razão da concomitância das 2 patologias já revelada na literatura.
Palavras-chave: thyroid nodule; fine needle aspiration of thyroid; thyroid cancer.
PO140 A SIMPLE METHOD OF SENTINEL LYMPH NODE
BIOPSY CAN UPSTAGE 50% OF N0 DIFFERENTIATED
THYROID CANCER
Steck JH1; Vasconcelos ECG2; Kulcsar MAV3; Bertelli AAT4; Hanaoka
N5; Linek M1
1
Hospital Mario Gatti; 2Federal University of Paraná; 3University of São
Paulo; 4Faculdade de Ciências Médicas da Santa Casa de São Paulo; 5Instituto
Nuclear de Ribeirão Preto (DIMEN)
Background: The standard method to detect neck metastases
for PTC is pre-operative ultrasound, but it has low sensitivity for the central neck. The interest for use Sentinel Lymph
Node (SLN) in clinically N0 Papillary Thyroid Cancer (PTC)
is increasing. Objective: This study aims to evaluate the effectiveness of a simple technique of SLN biopsy and its efficacy
in adequately stage the neck in cases of PTC. Methods: Forty
patients N0 PTC were submitted to surgery with intraoperative peri tumor injection of radiolabeled colloid (Fitato
Tc99). The procedure was Total Thyroidectomy, SLN localization with gamma probe and Central Neck Dissection
(CND). Results: We identified at least one SLN in 36/40. In
all patients at least one SLN was located in the Central Neck
and 4 had SLN located in Lateral Neck also. In 18 SLN were
positive at serial sections, and 55% of them had additional
metastasis on CND. The presence of central SLN metastases
upstaged the N0 PTC to N1a and lateral metastases upstaged tumors to N1b. The Sensitivity of SLN biopsy to diagnose
lymph node metastases was 94%, with 100% Specificity. The
Negative Predictive Value (NPV) was 94%. Conclusion: SLN
Biopsy has great accuracy to stage the Neck in N0 PTC, with
94% Sensitivity and 94% NPV. The benefit is avoiding unnecessary Neck Dissections and to upstage patients with occult
lateral neck metastases, which would benefit from further treatment with radioiodine.
Keywords: thyroid cancer; neck dissection; sentinel lymph
node.
PO141 COST OF ADJUVANT RADIOACTIVE IODINE
TREATMENT IN PATIENTS WITH DIFFERENTIATED THYROID
CARCINOMA
Goncalves Filho J1; Roque GRF1; Kowalski LP1
75
Abstracts: Poster
Background: The initial treatment of differentiated thyroid
carcinoma is based on surgery, and can be followed by iodine
therapy, according to the prognostic factors associated with
the tumor and the patient. However, controversy arises about
the necessity of the indications for adjuvant radioactive
iodine treatment. The objective of this study is to evaluate
the cost of radioactive iodine treatment in patients with welldifferentiated thyroid carcinoma. Patients and Methods: A
retrospective cohort study was performed using a prospectively maintained database of treatment costs of 115 patients
with well-differentiated thyroid carcinoma treated in the
period from 2008 to 2009, at a tertiary cancer hospital. There
were 101 women (88%) and 14 men (12%), with a mean age
of 40 years. Adjuvant treatment with radioactive iodine was
performed in 72 (62%) patients. The cost analysis data were
obtained from the computerized data base stored in prospective format, related to the number of procedures in a detailed, individualized form. Results: The total cost of adjuvant
treatment with radioactive iodine ranged from US$ 1,777 to
US$ 4,552 with a mean value of US$ 2,381 per patient, corresponding to a significant difference in cost in relation to that of
patients that did not require it. The increase in treatment cost
was also significantly related with radioactive iodine dose.
Conclusion: An analysis of the costs helps to rationalize the
use of resources. The unnecessary use of radioactive iodine in
patients without any real benefit would contribute significantly to avoid a rise in the costs of treatment.
Keywords: thyroid carcinoma; radioactive iodine; cost.
PO142 THE MAPK PATHWAY REGULATES TYPE 3
DEIODINASE EXPRESSION IN PAPILLARY THYROID
CARCINOMA
Romitti M1; Wajner SM1; Pinto Ribeiro RV1; Ceolin L1; Ferreira CV1;
Rohenkohl HC1; Fuziwara CS2; Kimura ET2; Maia AL1
1
Universidade Federal do Rio Grande do Sul (HC/UFRGS); 2Department of
Cell & Developmental Biology/Institute of Biomedical Science/São Paulo
University (USP) Thyroid hormone regulates several cellular and physiological
activities including the balance between cell proliferation and
differentiation. Pro-hormone T4 is converted into T3 by type 1
or type 2 deiodinases, while the inactivation of T4 and T3 occurs
by type 3 deiodinase (DIO3, D3). Recently we have demonstrated increased levels of D3 in PTC samples. D3 activity was
associated with tumor size and metastatic disease. Here we
aimed to determine the signaling pathways involved in D3 upregulation in PTC. Material and Methods: DIO3 expression
was evaluated in human PTC cell lines. DIO3 mRNA levels
were measured by Real-Time PCR and D3 activity by paper
descendent. MAPK effectors were evaluated using specific
inhibitors and protein expression was determined by Western
Blotting. Results: DIO3 mRNA and activity were readily detected in K1 (BRAF-mutated) and, at lower levels, TPC-1 (RET/
PTC1 rearrangement) cells. To evaluate the role of MAPK on
D3 induction, K1 cells were incubated with MEK (U0126)
and p38 (SB203580) inhibitors resulting in a dose-dependent
decrease in DIO3 mRNA and activity (~ 5 fold; p<0.001 and
~ 2 fold; p<0.01, respectively). Studies using a specific BRAFmutated inhibitor (PLX4032-5mM) have also demonstrated a
marked decrease on DIO3 levels (~ 12 fold; p<0,001). Further
76
analysis by Western blotting showed that the observed decreased on DIO3 levels were paralleled by a reduced steady-state
phosphorylation of the MAPK/ERK downstream effector, suggesting that this pathway is directly involved on D3 up regulation. Conclusions: The increased levels of D3 expression in
PTC are a consequence of constitutive activation of the MAPK
pathway caused by distinct genetic alterations.
Keywords: papillary thyroid carcinoma; deiodinase type 3;
MAPK pathway.
PO143 A RELAÇÃO DA POSITIVIDADE DOS ANTICORPOS
ANTIPEROXIDASE E ANTITIREOGLOBULINA COM A
MALIGNIDADE EM NÓDULOS TIREOIDIANOS
Colombo BS1; Silva MC1; Conceição TMB2; Canalli JS2; Pasinato
APBF1; Balthazar APS2; Canalli MHBS1,2 1
Hospital Universitário Polydoro Ernani de São Thiago/Universidade Federal de
Santa Catarina (HU/UFSC); 2Universidade do Sul de Santa Catarina (UNISUL)
Introdução: Relação entre autoimunidade e câncer tireoidianos ainda é desconhecida. Objetivo: Relacionar positividade
dos anticorpos antiperoxidase (anti-TPO) e antireoglobulina
(anti-TG) com malignidade em nódulos de tireoide (NT).
Material e métodos: Estudo transversal no HU/UFSC envolvendo 135 pacientes (138 nódulos tireoidianos – NTs), de
agosto de 2010 a agosto de 2012, com avaliações citológicas
e cito-histopatológicas (NTs operados + não operados com
citologias Bethesda II, V e VI) e anti-TPO e anti-TG por quimioluminescência. Dosagens bioquímicas foram realizadas à
época da punção aspirativa. Pacientes com disfunção tireoidiana estabelecida ou em tratamento foram excluídos. Análises
estatísticas foram efetuadas com teste do x2 ou Fisher e significância em p< 0,05. Resultados: Média de idade de 47,15 anos,
com 91,1% mulheres; 2,9%, 63%, 5,8%, 10,9%, 10,9% e 8,7%
dos NTs com Bethesda I a VI, respectivamente. Trinta e quatro
NTs foram operados, sendo 76,5% malignos e, desses, 80,8%
carcinomas papilíferos. Positividade para o anti-TPO (>35
mUI/mL) foi encontrada em 15,2% de 138 NTs e em 15,8%
(>40 mUI/mL) dos 95 casos analisados para anti-TG. Quatro
de 12 (33,3%) NTs Bethesda VI foram positivos para anti-TPO
e idem para anti-TG, enquanto 7 de 87 (8%) e 6 de 49 (12,2%)
NTs benignos (Bethesda II) foram positivos, respectivamente,
para anti-TPO e anti-TG. Apenas análises para anti-TPO atingiram significância estatística confirmada no estudo cito-histopatológico de 119 NT em que 8,8% de 91 NTs benignos e
25% de 28 NTs malignos apresentaram positividade para esse
anticorpo (p=0,024). Conclusão: Malignidade em NT relacionou-se com positividade para anti-TPO, necessitando-se maior
casuística para melhor avaliação do anti-TG.
Palavras-chave: nódulo de tireoide; câncer de tireoide; anticorpos antitireoidianos.
PO144 COMPARACIÓN DE TRES PROTOCOLOS
EXPERIMENTALES EN ESTUDIOS PRE CLÍNICOS PARA EL
TRATAMIENTO DEL CÁNCER DE TIROIDES, USANDO EL
BUTIRATO DE SODIO EN COMBINACIÓN CON LA TERAPIA
POR CAPTURA NEUTRÓNICA EN BORO (BNCT)
Perona M1; Majdalani E1; Carpano M2; Rodríguez C1; Nievas S1;
Olivera M1; Pisarev MA3; Cabrini R1; Juvenal G4; Dagrosa MA4 1
Comisión Nacional de Energía Atómica (CNEA); 2Comisión Nacional de Energía
Atómica; 3Comisión Nacional de Energía Atómica – CONICET, Facultad de
Medicina; 4Comisión Nacional de Energía Atómica (CNEA) – CONICET
Introducción: Previamente demostramos que BNCT podría
ser una alternativa para el tratamiento del cáncer de tiroides.
Abstracts: Poster
Los inhibidores de histonas deacetilasas, como el butirato de
sodio (NaB), son agentes antineoplásicos. Objetivo: Analizar
diferentes protocolos de combinación del NaB y del BPA
en ratones nude portadores de cáncer de tiroides humano.
Materiales y Métodos: Ratones nude fueron implantados con
células de carcinoma folicular humano de tiroides (WRO).
Se evaluaron tres protocolos: Protocolo 1: NaB administrado
a una dosis de 110 mg/kg p.c. vía i.p. 24 horas antes de la
administración de BPA; Protocolo 2: NaB 3,4% en el agua de
bebida (1 mes post-implantación) más BPA; Protocolo 3: BPA.
La dosis de BPA fue de 350 mg/kg p.c. y los animales fueron
sacrificados a las dos horas de haber sido administrada. Se
midió boro por ICP-OES en los tejidos y se realizaron análisis
histológicos. Resultados: Se observó un retraso en el crecimiento tumoral en el Protocolo 2. La concentración tumoral
de boro fue de 32,6 ± 1,4; 16,9 ± 3,7 y de 22,5 ± 0,9 ppm en los
Protocolos 1, 2 y 3, respectivamente. Los porcentajes de viabilidad y necrosis no variaron en los distintos protocolos. Se
observó mayor número de vasos y vacuolas y menor porcentaje de proliferación en el Protocolo 2. Conclusiones: Ambas
formas de administración del NaB podrían ser combinadas
con BNCT para optimizar el tratamiento del cáncer de tiroides. El crecimiento tumoral disminuyó en el Protocolo 2 y la
concentración tumoral de boro aumentó en el Protocolo 1.
Palabras clave: BNCT; butirato de sodio; cáncer de tiroides.
PO145 OPTIMIZACIÓN DE LA TERAPIA POR CAPTURA
NEUTRÓNICA EN BORO (BNCT) PARA EL TRATAMIENTO DEL
CÁNCER DE TIROIDES MEDIANTE EL USO DEL INHIBIDOR
DE HISTONAS DEACETILASAS BUTIRATO DE SODIO
Perona M1; Rodríguez C1; Carpano M1; Olivera MS1; Nievas S1; Thorp
S1; Curotto P1; Pozzi E1; Kahl S2; Pisarev MA3; Juvenal G4; Dagrosa MA4 1
Comisión Nacional de Energía Atómica (CNEA); 2Department of
Pharmaceutical Chemistry, University of California; 3Comisión Nacional
de Energía Atómica (CNEA) - CONICET - Facultad de Medicina (UBA);
4
Comisión Nacional de Energía Atómica (CNEA) - CONICET
Introducción: En estudios previos demostramos que la terapia
por captura neutrónica en boro (BNCT) podría ser una alternativa para el tratamiento del cáncer de tiroides. Objetivo:
Investigar el efecto del inhibidor de histonas deacetilasas
butirato de sodio (NaB) como radiosensibilizador de BNCT
para el tratamiento del cáncer de tiroides. Materiales y métodos: Se incubaron células de carcinoma folicular humano
de tiroides (WRO) con NaB 1 mM durante 24 h, y luego se
irradiaron con: 1) borofenilalanina (BPA, 10 mg10B/mL) +
neutrones; 2) 2,4-bis(a,b-dihydroxyethyl)-deutero-porphyrin
IX) (BOPP, 10 mg10B/mL) + neutrones; 3) Neutrones. Se evaluó la sobrevida celular, la muerte celular y la distribución en
el ciclo celular. Se realizaron estudios de biodistribución del
BPA (350 mg/Kg p.c.) en ratones nude implantados con células WRO, 24 horas luego de la administración de NaB (117
mg/kg p.c.). Resultados: La sobrevida celular disminuyó en
función de la dosis física absorbida. El NaB aumentó el efecto
(p<0,05). El NaB aumentó el porcentaje de células apoptóticas
y necróticas en los grupos BNCT (p<0,05). El NaB aumentó el
porcentaje de células arrestadas en la fase G2/M a las 24 horas
post-irradiación. Los estudios in vivo mostraron que el NaB
aumentó la captación tumoral de boro a las 2 h post-administración de BPA (p<0,01). Conclusiones: El butirato de sodio
podría ser utilizado como radiosensibilizador de BNCT para
el tratamiento del cáncer de tiroides.
Palabras clave: BNCT; cáncer de tiroides; radiosensibilizador.
PO146 EXPRESSION OF FAS, FASL, BCL-2 AND MCL-1
IN BENIGN THYROID NODULES WITH HASHIMOTO’S
THYROIDITIS: CLINICAL AND SONOGRAPHIC
CORRELATION
Maia FFR1; Vassallo J2; Pinto GA3; Pavin EJ1; Matos PS4;
Zantut-Wittmann DE1 1
Endocrinology Division/Department of Internal Medicine/Universidade
Estadual de Campinas (UNICAMP); 2Department of Pathology/Laboratory
of Investigative and Molecular Pathology/Centro de Investigações e Pediatria/
Universidade Estadual de Campinas (CIPED/UNICAMP); 3Faculty of Medical
Sciences, Laboratory of Specialized Pathology, LAPE/CAISM, UNICAMP;
4
Department of Pathology/Faculty of Medical Sciences/ Universidade Estadual
de Campinas (UNICAMP) Background: The molecular mechanisms regulating cell growth and death in thyroid adenomas are still poorly understood, including cases associated to Hashimoto’s thyroiditis
(HT). The correlation of clinical and ultrasound (US) features to apoptosis had not been previously study. Objectives:
Investigate the expression of Fas, FasL, Bcl-2 and Mcl-1 in
benign nodules associated to HT and correlates to clinical,
US and lab variables. Methods: We studied 55 euthyroid
benign nodules, 15 (27.3%) HT (study group) and 40 (72.7%)
non-HT (control group: 10 follicular thyroid adenoma, TFA
and 30, adenomatous goiter). The nodular area was staining
for Fas, FasL, Bcl-2 and Mcl-1 and compared to peritumoral
regions: normal adjacent tissue (control group) and HT area
(adjacent infiltrate lymphocytes; study group). Results: Bcl-2,
Mcl-1 and FasL were strongest in nodular than HT area in
study group (p<0.01). Fas staining were strongest observed
in HT and nodular area than normal tissue (p<0.001). The
goiter follicles cells showed the highest Bcl-2 and FasL staining (87.1% and 86.7%, respectively), followed by HT and
FTA areas. Mcl-1 was underexpressed in HT (33.3%) versus
TFA (20%) and normal areas (10%) (p=0.034). Multivariate
analysis showed correlation of apoptotic markers in nodular
area to suspect US features in control group (p<0.01) versus
HT group (p=0.70). Conclusions: Fas strong reactivity and
Bcl-2/Mcl-1 underexpression in HT’s tissue suggest induce
apoptosis. The pathogenic differences between nodules
associated or not to HT’s seem to be related to the apoptosis control, with a significant correlation to US features in
nodules without HT.
Keywords: thyroid nodules; Hashimoto’s thyroiditis; apoptosis.
Thyroid Nodule
PO147 APOPTOTIC MARKERS EXPRESSION IN THYROID
NODULES WITH A FIRST BENIGN CYTOLOGICAL RESULT
AND SUSPECT ULTRASOUND FOR MALIGNANCY
Maia FFR1; Vassalo J2; Pinto GA3; Pavin EJ1; Matos PS4;
Zantut-Wittmann DE1
1
Endocrinology Division/Department of Internal Medicine/Universidade
Estadual de Campinas (UNICAMP); 2Department of Pathology/Laboratory of
Investigative and Molecular Pathology/ Centro de Investigações e Pediatria/
Universidade Estadual de Campinas (CIPED/UNICAMP); 3Faculty of Medical
Sciences, Laboratory of Specialized Pathology, LAPE/ CAISM, UNICAMP;
4
Department of Pathology/Faculty of Medical Sciences/ Universidade Estadual
de Campinas (UNICAMP) Background: Thyroid malignancy detected after first benign
cytological result by serial examinations correlates to suspicious features at ultrasound (US) in 15 to 30% of the cases.
The FasL and p27 reactivity on thyrocytes would allow us
to understand the malignant rate in this specific group of
77
Abstracts: Poster
nodules. Objectives: Investigate the expression of apoptotic
markers (FasL; p27) in thyroid nodules with initially benign
cytology and suspect sonographic features. Methods: Off
143 thyroidectomies, we identified 35 nodules with suspect
US and benign cytology that underwent follow-up by annual
re-biopsies; 28.5% of them turned out malignant. FasL and
p27 immunochemical staining were carried in 21 off these
35 cases (study group), compared to a control group (with
negative US, n=29). Results: Off 50 thyroid nodules studied,
FasL was overexpressed in nodular (83.3%) vs. peritumoral
area (55.5%) from benign nodules of study group (18/21),
similar to control group (n=29, 93.1% ersos 72.4%, p=0.001);
in contrast to malignant tumors (3/21) which showed a
weaker staining in both areas (p=0.34). The p27 staining was
strongly observed in nodular (77.6%) vs. peritumoral area
(33.3%, p=0.003) in benign nodules of study and control
group (p<0.001); in contrast to malignant tumors in which
p27 was underexpressed (33.3% nodular versus 66.7%, peritumoral). Conclusions: Malignant tumors diagnosed after a
first benign cytology and suspect US features followed up by
serial re-biopsies showed FasL and p27 underexpression in
nodular area; in contrast to benign tumors which showed a
similar immunochemical profile to benign nodules without
suspect US features.
Keywords: thyroid nodule; thyroid cancer; apoptosis.
PO148 ALTERAÇÕES CITOLÓGICAS EM NÓDULO
TIREOIDIANO ASSOCIADO À DOENÇA DE GRAVES
Tonet C1; Corrêa MV1; Zorzo PT1; Rosa LCGF1; Costa GRG2;
Maia CP1; Mansur VAR1; Macedo LRW1; Messias ACNV1 1
Hospital Federal dos Servidores do Estado do Rio de Janeiro (HFSERJ); 2
Instituto de Pós-Graduação Médica Carlos Chagas (IPGMCC) Objetivo: Relatar caso de doença de Graves (DG) associado
a nódulo de tireoide suspeito de malignidade. Materiais e
métodos: Relato de caso e revisão de literatura sobre nódulo
de tireoide associado à DG. Resultados: Mulher, 25 anos,
relatava aumento de volume tireoidiano, perda ponderal,
cansaço e amenorreia. Ao exame físico: FC=144 bpm, pele
quente e úmida, tremores finos de extremidades, aumento
difuso da tireoide e ausência de atividade inflamatória ocular
(CAS=0). Laboratório: TSH suprimido e T4 livre e T3 elevados; TRAb positivo. Ultrassonografia (USG) de tireoide:
glândula aumentada, heterogênea, nódulo sólido de 14 mm
em lobo direito (LD). Cintilografia: nódulo hipocaptante,
hipercaptação do restante da glândula. Citopatologia (punção
aspirativa por agulha fina – PAAF): células foliculares agrupadas, às vezes com anisocariose, formando agrupamentos algo
papiliformes ou microfolículos. Optou-se pelo tratamento
cirúrgico, cujo histopatológico foi nódulo coloide. Discussão:
A associação de câncer de tireoide (CT) com DG ainda é alvo
de controvérsias. Já foi demonstrada a baixa incidência de
CT na DG, interrogando-se se esta seria um fator protetor.
Novos estudos, porém, mostraram a associação das 2 doenças, com incidência em até 21,5%, o que tornaria o CT mais
frequente na DG. A hipótese fisiopatológica é de que tanto o
TRAb quanto o TSH estimulariam o crescimento de nódulos
malignos, atuando como promotores da carcinogênese tireoidiana. A maioria dos guidelines recomendam a mesma abordagem de pacientes com nódulos sem outras tireoidopatias.
Conclusão: A investigação do nódulo na DG deve seguir a
mesma linha diagnóstica de pacientes eutireoidianos. Porém,
78
a presença do mesmo pode ser decisiva na escolha do tratamento cirúrgico do hipertireoidismo.
Palavras-chave: Nódulo de tireoide; doença de Graves; câncer de tireoide.
PO149 EVALUATION OF SERUM TSH AS A PREDICTOR
OF MALIGNANCY IN THYROID NODULES OF PATIENTS
SUBMITTED TO FINE NEEDLE ASPIRATION
Cristo AP1; Carlucci M1; Blom CB1; Faccin CS1; Goldstein HF1;
Maia AL1; Graudenz MS1 1
Hospital das Clínicas de Porto Alegre/Universidade Federal do Rio Grande
do Sul (HCPA/UFRGS) Background/Objectives: Currently the first choice of investigation in distinguishing benign from malignant disease is the
cytological analysis of fine needle aspiration biopsy (FNAB).
Previous studies have indicated that serum TSH levels might
be associated with the likelihood of malignancy. The aim
of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. Methods: One hundred consecutive patients,
who underwent FNAB as part of clinical investigation of
thyroid nodule in a multidisciplinary setting tertiary hospital,
underwent ultrasonography followed by FNAB, cytology and
cell block analysis. Independent-Samples Kruskal-Wallis test
was used to compare the groups. Results: The study population comprised of 86 female and 14 male patients. The mean
age was 54.7 years. Thirty-six per cent had previous thyroid
disease. Mean TSH and free T4 levels were respectively
2.42±2.96 and 1.56±1.95 uUI/mL. The mean nodule size was
2.43±1.31 cm. Final cytology/cell block diagnosis classified
6% as malignant, 63% as benign, 21% suspicious/indeterminate and 10% insufficient. The mean TSH values for benign,
suspect and malignant group were as follows: 2.14, 3.54, and
2.28 uUI/mL, respectively. No statistical significance was
detected between TSH levels and final diagnosis, possibly
reflecting the small sample size (p=0.63). Conclusions: These
data show a tendency for higher TSH values in individuals
with suspicious or malignant FNAB diagnosis, suggesting
that the likelihood of thyroid cancer increases with higher
serum TSH concentration.
Keywords: thyroid nodule; thyroid cancer; serum TSH.
PO150 NÓDULO DE TIREOIDE >4 CM: NECESSIDADE DE
CITOLOGIA ANTES DE TIREOIDECTOMIA?
Pacheco CFV1; Biancardi NF1; Biancardi MF1; Barcelos RN2 1
Centro Universitário Serra dos Órgãos (UNIFESO);2Universidade Federal de
São Paulo (UNIFESP) No manejo dos nódulos tireoidianos, faz-se necessário avaliação
ultrassonográfica (USG), hormonal e citológica. Em nódulos
grandes, com características de malignidade no USG, não está
indicada tireidectomia sem antes pesquisar citologia pela punção aspirativa por agulha fina (PAAF). Trata-se de M.C.G.B, 58
anos, do sexo feminino, mineira, moradora de Teresópolis-RJ.
Paciente veio ao serviço de endocrinologia no dia 3/8/2012 com
queixa de noctúria, polifagia, polidipsia e poliúria. Ao exame
físico, observou-se nódulo em região cervical direita, aparentemente fora da tireoide, móvel e de consistência endurecida.
Notou-se glândula tireoide com volume aumentado. Na ocasião,
foram solicitados exames para diagnóstico de diabetes mellitus tipo 2 (DM2), além de USG de pescoço, para avaliação do
nódulo/massa, e laboratório específico: TSH e T4 livre. Iniciado
Abstracts: Poster
tratamento de controle glicêmico na ocasião. Retornou no dia
22/8/2012 com resultados dos exames: teste de tolerância oral
glicose (TTOG): intolerância a glicose; Hba1c: 6,2%; glicemia
de jejum: 121mg/dL; outros resultados sem anormalidades:
TSH: 1,0 e T4 livre: 0,9. USG de pescoço evidenciou: glândula
tireoide aumentada de tamanho; lobo direito medindo 9,22 cm
x 3,66 cm x 4,78 cm, apresentando nódulo sólido isoecogênico
bem definido, contendo áreas císticas, vascularizado na periferia, medindo 6,34 cm x 3,91 cm. Encaminhada à Cirurgia Geral.
Tireoidectomia parcial em 16/10/2012 com biópsia de congelação do nódulo, apresentando aspecto de benignidade. Ao histopatológico, temos: carcinoma folicular com infiltração da cápsula e invasão vascular limitada à cápsula. Encaminhada para
nova cirurgia. A questão é: a PAAF torna-se necessária mesmo
em pacientes com nódulos grandes? A PAAF evitaria reabordagem cirúrgica, uma vez que essas cirurgias poderiam ser resolutivas em um primeiro tempo?
Palavras-chave: nódulo tireoidiano; tireoidectomia total;
carcinoma folicular de tireoide.
PO151 VALOR DIAGNÓSTICO DA PUNÇÃO ASPIRATIVA DA
TIREOIDE (PAAF): ESTUDO COMPARATIVO DA TÉCNICA
COM E SEM USO DA ULTRASSONOGRAFIA
Alcântara-Jones DM; Lavinas-Jones JM; Daltro R; Pitangueira AC;
Alcântara FT; Cardeal M; Araújo LMB 1 1
Hospital São Rafael/Universidade Federal da Bahia (HSR/UFBA) Introdução: Buscou-se avaliar quanto a experiência com a
técnica e o uso da ultrassonografia (USG) modificam o poder
de diagnóstico da punção aspirativa por agulha fina (PAAF).
Material e métodos: A PAAF é comparada em 2 momentos,
com 2 diferentes grupos de pacientes, portadores de bócios
nodulares. No grupo 1 (G1), de 113 pacientes avaliados por palpação, 50 foram selecionados para a cirurgia. No grupo 2 (G2),
a PAAF foi guiada pela USG e 49/1055 foram operados. Em
ambos os grupos, a técnica foi realizada pelo mesmo observador. Resultados: Entre os pacientes operados, em G1 (3 do sexo
masculino e 47 do sexo feminino), o percentual de material insatisfatório foi de 24%, e a seleção para a cirurgia baseou-se em
dados clínicos. Em G2 (7 homens e 32 mulheres), o percentual
de material insatisfatório foi 7,8%. Os valores de sensibilidade,
especificidade, VPP e VPN de G1 e G2, foram respectivamente:
40% e 80%, 71% e 100%, 100% e 100%, 97% e 89,5%. Em G1,
obteve-se 5 (10%) casos de câncer, enquanto, em G2, obteve-se
32 (65,3%) casos. Discussão: A melhor seleção para a tireoidectomia esteve associada à maior experiência com a técnica e à utilização da USG. O que foi sensivelmente diferente nas 2 amostras é que com a orientação da USG conseguiu-se diagnosticar
câncer em nódulos subcentimétricos, possibilitando diagnóstico
mais precoce, constatando-se inclusive maior número de câncer
entre os menores que 1 cm. Conclusão: A experiência do observador com a técnica de PAAF e a utilização da USG produzem
um melhor desempenho do exame.
Palavras-chave: thyroid nodule; thyroid cancer; fine needle
aspiration of thyroid.
PO152 HYPOTHYROIDISM FOLLOWING THYROID
LOBECTOMY: HOW TO PREDICT?
Lira RB1; Viana ARO1; De Carvalho AY1; Kowalski LP1
Department of Head and Neck Surgery and Otorhinolaryngology/Hospital A
C Camargo 1
Background: Hypothyroidism is the most frequent complication after thyroid lobectomy. Preoperative prediction for
this complication may be helpful in therapeutic decision
making in patients candidates for this procedure. Objectives:
To analyse potential risk factors of hypothyroidism following
hemithyroidectomy and develop a simple risk classification. Methods: We retrospectively analyzed 125 consecutive
patients submitted to thyroid lobectomy from 2008 to 2010.
The median age of the patients was 44 years and 106 if them
were women (84.8%). The pathological examination of surgical specimens showed 8 cases of low risk papillary carcinoma and 117 benign diseases, with minimal follow-up of 12
months. Results: We analyzed the sensitivity and specificity
of preoperative TSH and intraoperative volume of ressected
lobe as potential predictors of hypothyroidism after thyroid
lobectomy by means of a R.O.C. So we developed a simple 3
group classification (low, intermediate and high risk) based
on the presence of none, 1 or 2 of this risk factors (high TSH
and low volume of ressected lobe). Applying this on our cases,
we had 24.1%, 43.1% and 76.3% of postoperative hypothyroidism in the low (volume >8 mL and TSH<1.5), intermediate
(volume <8 mL or TSH>1.5) and high risk (volume <8 mL
and TSH>1.5) groups, respectively. (p<0.001). Conclusions:
Preoperative TSH>1.5 mUI/L and volume of resected thyroid
lobe <8 mL were the most significantly factors associated
hypothyroidism after hemithyroidectomy. An easily reproducible preoperative classification based on both this risk
factors can be useful in therapeutic decision making (total
versus partial thyroidectomy).
Keywords: thyroid lobectomy; hypothyroidism; TSH.
PO153 AVALIAÇÃO DO USO PROLONGADO DO ÁCIDO
RETINÓICO NO CARCINOMA AVANÇADO DA TIREOIDE –
ESTUDO FASE II
Snaider M1; Mello RCR1; Vaisman M1
Universidade Federal do Rio de Janeiro (UFRJ) 1
Introdução: Cerca 30% dos pacientes com carcinoma de
tireoide metastático apresentam perda da diferenciação celular e resistência à terapia convencional. Estudos mostram
que o acido retinoico (AR) pode induzir recaptação de iodo
e regressão do tumor. Como o AR possui efeito de apoptose
e antiangiogênico, o uso prolongado dessa droga pode determinar regressão em alguns casos. Objetivo: Avaliar o efeito
do uso prolongado do AR em pacientes com câncer avançado
de tireoide de linhagem folicular. Método: Seis pacientes
com carcinoma da tireoide de origem folicular com doença
irressecável e/ou níveis de tireoglobulina sérica persistentemente elevados e resposta ausente ou incompleta à radioiodoterapia receberam isotretinoína por via oral, na dose
de 0,5-1,0 mg/kg/dia, ajustada conforme tolerabilidade por
5-9 meses, acompanhados com consulta ambulatorial mensal. Foram realizados exames laboratoriais e de imagem no
início do acompanhamento e ao término. Resultados: Não
houve mudança do status de doença inicial. Não houve efeitos
colaterais graves. O aumento da tireoglobulina em 4 pacientes não foi acompanhado de piora da doença nos pacientes
que não apresentavam progressão antes da medicação. Houve
retorno dos valores da tireoglobulina para próximo dos
valores iniciais após suspensão da medicação em 2 destes 4
pacientes, sugerindo proteína provavelmente rediferenciação,
fato já relatado em trabalhos anteriores. Discussão: O AR não
79
Abstracts: Poster
parece ainda ser uma opção de tratamento isolado para os
pacientes com câncer avançado de tireoide. Não houve diferença no quadro clínico dos pacientes. Novos estudos sobre
expressão de receptores e sua função na progressão da doença
são necessários.
Palavras-chave: ácido retinoico; carcinoma de tireoide; novos
tratamentos.
PO154 PERSISTENCY OF PAPILLARY THYROID
CARCINOMA: MULTIPLICITY AS A PROGNOSTIC FACTOR
IN LOW RISK PATIENTS
Silva PCA1; Silva MNC2; Colombi AS2
Pediatric Endocrine Division/Joana de Gusmão Children’s Hospital; 2Thyroid
Unit/São José General Hospital/Universidade Sul de Santa Catarina School of
Medicine (UNISUL) 1
Introduction: The presence of recurrent cervical lymphadenopathy is an increasingly common problem in clinical practice in the treatment of thyroid cancer. Objectives: To observe
whether factors such as multiplicity would be associated
with recurrence of papillary thyroid carcinoma. Methods:
A retrospective study of medical records of 250 patients
(mean follow-up of 10.6 years) and selected patients with Tg
levels >2.0 ng/dL after undergoing total thyroidectomy for
papillary carcinoma papillary follow by classic dose of 100
mCi of 131-I. Results: Twenty-six patients (9 females, 49±15
years-old, 17 males, 45±15 years-old) persisted with disease
(10%). Of these, 34% (n=10) were single nodules (6 pappilary pure and 3 pappilary/folicular) versus 62% (n=16) with
multicentric type. Single and larger nodules were more localized on isthmus and left lower lobe near the glandular capsule. Multiplicity was detected after surgery in 70% of patients
with > 1 nodule in ultrasound. Relapse occurred in 55% of the
contralateral side in patients undergoing removal of lymph
nodes. Conclusion: In our series, multiplicity is associated
with persistence of papillary thyroid carcinoma.
Keywords: multiplicity; persistency; thyroid cancer.
PO155 TSH PREQUIRÚRGICA COMO FACTOR
PRONÓSTICO (FP) EN EL CÁNCER DIFERENCIADO
DE TIROIDES
Villa S1; Seleme S1; Cabrera S1; Vacchiano V1; Sciorra J1;
Rodríguez P1; Corino M1
1
Hospital Nacional Profesor A. Posadas Objetivo: Correlacionar TSH prequirúrgica con FP clínicos e histológicos del cáncer tiroideo. Material y método:
Analizamos 83 pacientes con cáncer de tiroides y tiroidectomía total (3/ 2004-2/2011). Se excluyeron 31 por no cumplir con el protocolo. N: 52 restantes consideramos asociación TSH prequirúrgica y FP: edad, sexo, histología, tamaño
tumoral, uni/multifocalidad, invasión capsular, angiolinfática
extensión extratiroidea, metástasis ganglionar y a distancia.
Consideramos alto riesgo a: >45 años, masculino, variantes
histológicas: folicular y oncocítico, tumor >4 cm, multifocalidad, invasión capsular, vascular, peritiroidea, compromiso ganglionar o a distancia. La TSH dividida en cuartilos: 1º < a 1,11(n:13), 2º 1,11-1,87(n:14), 3º 1,88-3,13(n:12)
y 4º > 3,13(n:13). Utilizamos test ANOVA, Kruskal Wallis,
Chi cuadrado y regresión logística múltiple para evaluar
TSH. Resultados: N 52 mediana 38 años (rango: 16-76),
femeninos 86,5%. Mayor prevalencia de mujeres con TSH
más alta (p=0,05). Mediana de TSH 1,87 (rango: 0,02-74).
Mayor prevalencia de papilar clásico para TSH por debajo
80
de la mediana y mayor prevalencia de carcinoma folicular;
papilar variante folicular y oncocítico para TSH encima de
la misma (p=0,02). No hubo asociación ES entre las demás
variables El 86,5% fue alto riesgo. El análisis de regresión
logística múltiple, alto o bajo riesgo, no encontró TSH predictora de alto riesgo (OR=1,08 p=0,73). El 76,9% en el cuarto
cuartil fue multifocal (p=0,17). Conclusión: Comprobamos
una relación ES entre TSH y las variantes histológicas agresivas. No hallamos asociación con el resto de los factores pronósticos. Encontramos mayor presentación multifocal para
valores mayores de TSH.
Palabras clave: TSH; carcinoma; riesgo.
PO156 EVALUATING THE PROGNOSTIC FACTORS
ASSOCIATED WITH CANCER-SPECIFIC SURVIVAL IN WELL
DIFFERENTIATED THYROID CARCINOMA IN PATIENTS > 45
YEARS
Quiroa LR1; Goncalves Filho J1; Kowalski LP1
Background: Well-differentiated thyroid carcinoma (WDTC)
usually has a good prognosis. However, various clinical and
pathological factors have been described associated with survival, among these, age >45 years is the most important prognostic factor. Objective: The objective of this study is to evaluate
the prognostic factors associated with cancer-specific survival
of well-differentiated thyroid carcinoma in patients older than
45 years. Patients: Four hundred and forty-three consecutive
patients undergoing treatment with curative intent were retrospectively studied. Three hundred ninety-six patients (89%) had
papillary carcinoma and 47 had follicular carcinoma (11%).
There was stage T1 in 326 (73.6%), T2 in 45 (10.2%), T3 in 39
(8.8%), and T4 in 31 (7.5%). Total thyroidectomy was the surgical procedure in 368 patients (83%), partial thyroidectomy in
45 (10%), and extended thyroidectomy in 30 (7%). A total of 66
patients (15%) were pN+. Results: Thyroid carcinoma-related
survival in 10 years was 91% for the whole group. Univariate
analysis showed that age >60 years, tumor size larger than 2
cm, staging T3-T4, positive lymph nodes, distant metastases, follicular histology, vascular and lymphatic invasion, and
extrathyroid extension were associated with decreased survival. Multivariate analysis identified age, tumor size, distant
metastasis at the time of presentation, vascular and lymphatic
invasion to be significant independent prognostic factors affecting survival. Conclusion: Assessment of prognostic factors in
patients older than 45 years showed that age >60 years, follicular histology, tumor size, distant metastasis and presence of
vascular and lymphatic invasion were the independent predictors of survival.
Keywords: thyroid cancer; prognostic factors; survival.
PO157 ANALYSIS OF ADENOSINE MONOPHOSPHATEACTIVATED PROTEIN KINASE (AMPK) SIGNALING
IN DIFFERENTIATED THYROID CARCINOMA BY
IMMUNOHISTOCHEMISTRY
Vidal APA1; Amdreade BM1; Vaisman F1; Cazarin J1; Pinto LF2; Beitenbach MMD2; Corbo R1; Vaisman1; Caroli-Bottino A1; Carvalho DP1
1
Universidade Ferderal do Rio de Janeiro (UFRJ); 2Instituto Nacional do
Cancer (INCA) Background: AMPK kinase is activated by depletion of cellular
energy. Once phosphorylated, AMPK allows adaptive changes
Abstracts: Poster
in metabolism leading to changes in cell growth and differentiation. The role of AMPK signalling pathway in carcinogenesis has not been determined yet. Objectives: Evaluate AMPK
expression and phosphorylation in differentiated thyroid carcinoma samples and compare with their non-neoplastic counterparts by immunohistochemistry. Methods: 107 specimens of
thyroid carcinoma, 84 papillary and 23 follicular, and their nonneoplastic counterparts were selected to a tissue microarray
block. Immunohistochemical staining was performed for total,
phospho-AMPK and phospho-ACC. Two observers evaluated the slides and scored semi-quantitatively for both intensity
(graded 0-3) and proportion (graded 1-6) of cytoplasmic staining. We used the multiplication of both scores to quantify the
expression and activity of AMPK. Results: There is an increase
in total AMPK score in 87 (81%) of the thyroid carcinoma specimens, as diffuse and strong staining of the cytoplasm (15.2±3.3)
compared to focal expression in normal epithelium (13.9±4.9),
with significant association (p=0.034). Phospho-AMPK was
higher in 89 (88%) (12±5) x (7.6±4.9) and phospho-ACC in
101 (96%) (11.3±5) x (5.8±4.2) of the carcinomas. No distinct
score pattern was seen between papillary and follicular carcinomas. Conclusion: Significantly increased AMPK and ACC
phosphorylation signals were seen in thyroid carcinoma specimens when compared with the expression in the non-neoplasic
counterparts. No distinct pattern was detected between papillary
and follicular carcinomas. We conclude that AMPK might be
implicated in thyroid cancer cell transformation.
Keywords: AMPK; thyroid; carcinoma.
PO158 EFECTO DE TGF-B1 SOBRE ENZIMAS REDOX
Y EN EL CONTROL DEL CICLO CELULAR EN CÉLULAS
TIROIDEAS NORMALES Y TUMORALES
Oglio R1; Thomasz L2; Salvarredi L1; Juvenal G2; Pisarev M3 1
CNEA; 2CNEA, Conicet; 3CNEA, UBA, CONICET Introducción: Demostramos que TGF-b1 inhibe la proliferación y aumenta las especies reactivas del oxígeno en células tiroideas. Objetivos: Evaluar el efecto del TGF-b1 sobre
enzimas redox y el control del ciclo celular. Procedimiento:
Se trataron células de cáncer humano folicular (WRO) y de
tiroides normal de rata (FRTL-5) con 5 ng /mL de TGF-b1.
Se evaluó la distribución del ciclo celular, la expresión y la
localización de p21 y p27. Además, se estudió la expresión de ciclinas A, D1, D2 y CDK-4 en WRO. En cuanto a
las enzimas redox, se evaluó la actividad de catalasa (CAT)
y glutation peroxidasa (GPx) y niveles de mRNA de CAT,
GPx, Superóxido dismutasas (SOD1, SOD2), Thox1 y
Thox2. Resultados: TGF-b1 aumentó la población celular en
G1(25%) en FRTL-5 y en G2/M(30%) en WRO (48h; p<0,05).
TGF-b1 indujo un incremento en la expresión de P27 en
FRTL-5(p<0,05) pero no su translocación al núcleo. En WRO
indujo la translocación de P27 y P21 al núcleo y disminuyó la
expresión de ciclina D2 y CDK-4 (72h; p<0,05). En cuanto a
las enzimas redox, la actividad de catalasa disminuyó al 50%
en ambas líneas (72h; p<0,01) y no se detectaron cambios en
GPx. Los niveles de mRNA de SOD1, CAT, Thox1, Thox2 se
encontraron disminuidos en FRTL5, mientras que en WRO
se observó la disminución de SOD1 y un incremento de GPx
(24h; p<0,05). Conclusiones: TGF-b1 inhibe la proliferación
celular mediante el arresto celular y podría regular la expresión de enzimas involucradas en el balance redox celular.
Palabras clave: TGF-beta 1; ciclo celular; ROS.
PO159 ROLE OF TOLL LIKE RECEPTOR 4 IN THYROID
CARCINOGENESIS INDUCED BY THE ONCOGENE BRAF
V600E
Nazar M1; Peyret V1; Nicola JP1; Pellizas CG1; Masini-Repiso AM1
CONICET) 1
Background: Toll Like Receptors (TLRs) are transmembrane
proteins that recognize specific patterns of pathogens, and its
deregulation has been implicated in cancer. We have shown
that TLR4 is functionally expressed in normal thyrocytes,
although its role in human thyroid pathologies remains unidentified. Objective: To study the role of TLR4 in the development and progression of thyroid cancer. Methods: PC-BRAF
cell line, a TET-ON system in which PCCL3 thyroid cells
express the BRAF V600E oncogene when treated with
doxycycline; WB; immunohistochemistry; promoter activity
(luciferase) and RT-qPCR. Results: Immunohistochemistry
of thyroid carcinoma tissues showed an aberrant TLR4 overexpression compared to normal tissue. Doxycycline-treated
PC-BRAF cells increased TLR4 expression in a time-dependent manner, which proved to be functional by responding to
treatment with lipopolysaccharide increasing the expression
of the responsive genes IL-6 and iNOS. The augmented TLR4
expression involves, at least in part, the transcriptional level
as demonstrated by promoter and mRNA assays. WB analysis
showed an increased serine 276 phosphorylation in response
to BRAF V600E expression. Moreover, co-transfection assays
of a NF-kB reporter vector together with mutant p65 expression vector in which serine 276 is non-phosphorylatable,
corroborated its role in BRAF V600E-induced p65 activation. Interestingly, PCCL3 normal cells cultured with BRAF
V600E-transfected cells-conditioned mediums showed an
increased p65 activity, demonstrating the presence of soluble factors secreted by transformed-cells able to alter normal
cell behavior. Conclusions: TLR4 functional over-expression
was demonstrated in BRAF V600E-transformed thyroid cells,
entailing new evidence related to its participation in the development and progression of thyroid cancer disease.
Keywords: TLR4; BRAF V600E; thyroid.
PO160 BRAF V600E ONCOGENE EXPRESSION AND TLR4
ACTIVATION MODULATE EPIDERMAL GROWTH FACTOR
RECEPTOR (EGFR) IN THYROID TRANSFORMED CELLS
Peyret V1; Nazar M1; Nicola JP1; Pellizas CG1; Masini-Repiso AM1
CONICET) 1
Background: Increased expression of Epidermal Growth
Factor Receptor (EGFR) in human thyroid carcinoma is considered a marker of tumor progression. The Toll-like receptor
4 (TLR4) has been involved in several human carcinomas. We
have demonstrated an increased TLR4 expression in human
thyroid carcinoma tissues and cell lines. We demonstrated
that the induction of the oncogene BRAF V600E in the normal rat thyroid cell line PCCL3 enhances TLR4 expression. A
transactivation of the EGFR pathway after activation of TLR4
has been described in various human cancers. Methods:
Culture of human thyroid anaplastic carcinoma cell line
8505c; PC-BRAF cell line, a TET-ON system in which PCCL3
thyroid cells express BRAF V600E oncogene when treated with
doxycycline; Western Blot (WB). Objective: To analyze the
effect of BRAF V600E oncogene induction on EGFR expres-
81
Abstracts: Poster
sion in PCCL3 and a possible interaction among TLR4 stimulation and EGFR activation. Results: High EGFR expression
was displayed (WB) in the BRAF V600E-expressing 8505
cells. When these cells where stimulated by the TLR4 ligand
lipopolysaccharide (LPS) an increase of EGFR phosphorylation was observed at 30 and 45 min. The expression of EGFR
in time course experiments where doxycycline was added to
the culture medium of PC-BRAF cells for 3 days showed that
the presence of the BRAF V600E oncogene increased EGFR
expression in PC-BRAF cells. Conclusions: It was concluded
that the high EGFR expression in human tumor cells could be
associated with BRAF V600E oncogene expression. A TLR4dependent EGFR transactivation in human thyroid cancer
cells is suggested.
Keywords: EGFR; TLR4; BRAF V600E.
PO161 TUMOR DE CÉLULAS REDONDAS NA CITOLOGIA
TIREOIDIANA: RELATO DE CASO
Sasson P1; Santos JCV 1; Magalhães RSC1; Reis MDSLC 1; Maia CP 1;
Mansur VAR 1; Corrêa MV 1; Macedo LRW 1
1
Hospital Federal dos Servidores do Estado (HFSERJ) Introdução: Células redondas encontradas durante exame
anatomopatológico da tireoide estão contidas em um grupo
heterogêneo de afecções de grande complexidade. Sabe-se
que na grande maioria dos casos está associado a tireoidite
de Hashimoto, porém o diagnóstico diferencial deve ser feito
principalmente com o carcinoma medular da tireoide e plasmocitoma. Objetivo: Relatar caso de carcinoma medular da
tireoide diagnosticado inicialmente como tumor de células
redondas. Métodos: M.S.S, do sexo feminino, 35 anos, realizou tireoidectomia subtotal há 1 década devido a adenoma
folicular, porém surgiu novo nódulo de cerca de 2 cm em
tecido tireoidiano remanescente há 4 anos. Foi realizada punção aspirativa por agulha fina (PAAF) em 2008, cujo diagnóstico sugeriu nódulo coloide. Devido a crescimento nodular, a
PAAF foi repetida em 2012 e foi visualizado tumor de células redondas com configuração plasmocitoide. Solicitou-se
adicionalmente dosagem de calcitonina sérica. Resultados:
Nova revisão de lâmina com suspeita citopatológica de carcinoma medular que foi confirmada após nova cirurgia. A
dosagem de calcitonina foi de 299 pg/mL. Conclusão: O carcinoma medular da tireoide pode apresentar-se como tumor
de células redondas no histopatológico e devido à variedade
de diagnósticos diferenciais pode não ser diagnosticado pela
PAAF, o que representa um grande impacto clínico na evolução do paciente. É necessário destacar a importância do seu
achado no diagnóstico de carcinoma medular da tireoide e
outros diagnósticos diferenciais.
Palavras-chave: células redondas; carcinoma medular; diagnóstico diferencial.
Iodine Deficiency
PO162 YODURIA EN ADULTOS SANOS
Flores-Rebollar A1; Lendechy-Velázquez M1; Castro-Sánchez A1;
López-Carrasco G1; Estrada-Joe LI1; Ruiz-Juvera A1; Martínez C2;
González-Treviño O1 1
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”;
2
Instituto de Nutrición de Centroamérica y Panamá (INCAP) Introducción: El estatus nutricional del yodo en una población es medido, principalmente, por la excreción del yodo
urinario. La vigilancia nutricional del yodo en la población
82
en México ha sido escasa. La última encuesta nacional se
realizó hace una década. Objetivo: Determinar la yoduria
en una muestra ocasional, en adultos sanos que habitan en
un área urbana. Métodos: Es un estudio transversal para el
que se seleccionó una muestra de individuos mayores de 18
años, entre médicos residentes y trabajadores administrativos
de nuestra institución. Todos sanos y sin enfermedad tiroidea
conocida. A todos los voluntarios se les solicitó una muestra
de orina entre las 8 h y las12 h de la mañana. La orina se
mantuvo en refrigeración a -20ºC hasta su análisis. Se determinó la yoduria en una técnica de microplaca basada en la
reacción de Sandell-Kolthoff. Resultados: Participaron 102
voluntarios, con una edad promedio de 29 años, siendo que
había más hombres que mujeres (59/43). El promedio de la
yoduria del grupo total fue 221 mg/L, RIQ (135,0 a 356,8).
No hubo diferencias entre géneros. Las mujeres tuvieron una
yoduria de, 218.0 mg/L RIQ (129,0 a 351,0) vs 223,0 mg/L RIQ
(138,0 a 374,0) p 0.941. El 31,4% de los voluntarios mostraron
una yoduria en exceso. Conclusiones: La yoduria determinada en este grupo presentó, en media, una ingestión más que
adecuada de yodo en la dieta, de acuerdo con la clasificación
de la OMS/ICCIDD. Esto lo coloca en riesgo de sufrir distiroidismo. Es necesario considerar la evaluación Nacional del
estatus nutricional del yodo en México.
Palabras clave: yodo en orina; exceso de yodo; disfunción
tiroidea inducida por yodo.
PO163 VALORES DE REFERENCIA DEL VOLUMEN
TIROIDEO EN ADULTOS, DETERMINADO POR
ULTRASONOGRAFÍA
Flores-Rebollar A1; Castro-Sánchez A1; López-Carrasco G1; KananFalcón M1; Ruiz-Juvera A1; González-Treviño O1 1
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”
Introducción: La ultrasonografía (US) ha probado ser una
herramienta práctica y útil para la evaluación del tamaño tiroideo. La disponibilidad de equipos de ultrasonido portátiles
facilita su aplicación en estudios epidemiológicos. Objetivo:
Determinar los valores de referencia del volumen tiroideo, en
una población de individuos sanos. Métodos: Se estudiaron
427 voluntarios sanos (186 hombres, 241 mujeres) reclutados
del personal médico de nuestro hospital. Se excluyeron enfermos tiroideos, con comorbilidad o tomando medicamentos
que pudieran interferir con la función tiroidea. La edad promedio fue 26 años IQ (24-30). El US tiroideo se realizó con
un equipo portátil. Se les determinó anticuerpos antiperoxidasa tiroidea (TPO), antitiroglobulina (TGAb), TSH y T4 L. Resultados: Se formó una población de referencia de 275 individuos. Los 152 excluidos tuvieron una o más razones para su
exclusión: 53 por la presencia de anticuerpos antitiroideos,
59 por AHF de distiroidismo, 24 tuvieron una TSH fuera del
rango de 0,27 a 3,37 mUI/L y a 39 se les detectó nodulaciones.
La distribución del volumen tiroideo (VT) no fue Gaussiana y
se requirió la trasformación logarítmica. El VT total promedio del grupo fue 8,83±1,5 (p50 9,3 y p97,5 18,1 mL). El VT
total promedio para hombres fue 10,2±1,4 (p50 10,2 y p97,5
19,4 mL) y el VT total promedio en mujeres, 7,6±1,5 (p50
7,5 y p97.5 16.0 mL), p<0.0001 (ANOVA). Conclusiones: Por
vez primera, en México, se define un valor de referencia para
VT por US en una población sin deficiencia en yodo.
Palabras clave: volumen tiroideo; ultrasonido; valores de
referencia.
Abstracts: Poster
PO164 THYROGLOBULIN IS A SENSITIVE MEASURE
OF BOTH DEFICIENT AND EXCESS IODINE INTAKES IN
CHILDREN AND INDICATES NO ADVERSE EFFECTS ON
THYROID FUNCTION IN THE UIC RANGE OF 100-299
MG/L.STUDY OF PARAGUAY COMPARING WITH OTHER
COUNTRIES
Jara Yorg JA; Zimmerman MB; Aeberli I; Anderson MI; Timmer A;
Pretell E; Jara MA; Jara Ruiz JM; Jara Ruiz ED; Benitez D1
1
International Council for the Control of Iodine Deficiency Disorders/
Paraguay (ICCIDD) Background: The median urinary iodine concentration
(UIC), used to monitor universal salt iodization (USI), is a
biomarker of iodine intake. Thyroglobulin (Tg) is a promising functional iodine status biomarker. Objectives: Our
study aims were to, in school-age children: 1) evaluate the
response of a standardized DBS-Tg assay to low and high
intakes of iodine; 2) estimate the population cut-off point
for using DBS-Tg to define iodine deficiency or excess; and
3) to compare thyroid function over the range of iodine
intakes currently defined by the WHO as adequate (UIC,
100-199 mg/L) and ‘more-than-adequate’ (UIC, 200-299
mg/L). Methods: In an international cross-sectional study of
6 to 12-year-old children (n=76) with varying iodine status,
UIC, TSH, thyroxine (T4), Tg and thyroid antibodies were
measured in Paraguay. Results: Tg concentrations showed
a clear U-shaped curve. Compared to iodine sufficient children, there was a significantly higher prevalence of elevated
Tg values in children with iodine deficiency (UIC<100 mg/L)
and iodine excess (UIC>300 mg/L). There was no significant
change in Tg, TSH, T4 or thyroid Abs comparing children
across the current WHO UIC ranges of adequate and ‘morethan-adequate’ iodine intake. Conclusions: In children: a) Tg
is a sensitive indicator not only of low iodine intakes but also
of excessive intakes; b) a median Tg of <12 mg/L or <3% of Tg
values >40 mg/L indicates iodine sufficiency; c)the acceptable
range of median UIC in USI monitoring guidelines could be
widened to adopt a single category of ‘sufficient iodine intake’
in the range of 100-299 mg/L.
Keywords: iodine excess; iodine deficiency; thyroglobulin.
PO165 URINARY IODINE CONCENTRATION AND THYROID
VOLUME IN OVERWEIGHT AND OBESE SCHOOLCHILDREN
IN QUERETARO CITY, MEXICO
Méndez-Villa L1; Sampson-Zaldívar E2; Robles-Osorio L1; Solís-S JC1;
García-Solís P1
1
Department of Biomedical Research/School of Medicine/Universidade
Autônoma de Querétaro (UAQ); 2Department of Radiology/Vida Care
Diagnostics Background: Childhood obesity is a public health problem
worldwide. Previous data from our group showed a significant relation between iodine excess and overweight and obesity (unhealthy weight). In addition, it has been shown that
obesity and excessive iodine intake may increase the risk of
thyroid disease. Objective: To compare urinary iodine concentration (UIC) and thyroid volume (Tvol) in schoolchildren with healthy and unhealthy weight from Queretaro city.
Methods: A cross sectional survey was performed in 678
schoolchildren. UIC was determined by the Sandell-Kholtoff
method and the median of UIC was estimated. Tvol was measured by ultrasound, body mass index was used to determine
the nutritional status; both variables were determined according to the WHO criteria (2007). Results: The unhealthy wei-
ght prevalence was 47.2%. The median UIC was 428 mcg/L.
There was not a significant difference between median UIC
between schoolchildren with unhealthy and healthy weight,
421 versus 436 mcg/L, respectively. Tvol of boys aged 6 years
was significantly higher in those with unhealthy weight than
with healthy weight. Moreover, Tvol of girls aged 8, 10 and 12
years was significantly higher in those with unhealthy weight
than with healthy weight. Conclusions: Median UIC of schoolchildren indicated an excessive iodine intake. Besides, girls
with unhealthy weight consistently had a higher Tvol than
those with healthy weight. More studies are needed to investigate the role of excessive iodine intake and unhealthy weight
in the development of thyroid disease.
Keywords: iodine nutrition; schoolchildren; thyroid volume.
PO166 ASSESSMENT OF IODINE NUTRITION AND THYROID
FUNCTION IN MEXICAN WOMEN OF REPRODUCTIVE AGE
Méndez-Villa L1; Elton-Puente JE2; Sampson-Zaldívar E3;
García-Gutiérrez C4; Villalobos P5; Robles-Osorio L4; Solís-S JC4;
Colarossi A6; García OP2; García-Solís P4
1
Department of Biomedical Research/School of Medicine/Universidade
Autônoma de Querétaro (UAQ); 2School of Natural Sciences/Universidade
Autônoma de Querétaro (UAQ); 3Department of Radiology/Vida Care
Diagnostics; 4Department of Biomedical Research/School of Medicine;
5
Institute of Neurobiology/Universidad Nacional Autónoma de México
(UNAM); 6Department of Cellular and Molecular Sciences/School of Sciences
and Philosophy/Universidad Peruana Cayetano Heredia (UPCH) Background: Thyroid hormones are essential for multiple
processes related to growth, development and reproduction.
An adequate iodine intake is required for normal thyroid
function. Objective: To assess iodine nutrition and thyroid
function in Mexican women of reproductive age. Methods: A
descriptive cross-sectional study was performed in 101 women
in reproductive age randomly selected from the Autonomous
University of Queretaro. Serum levels of TT4, FT4, TT3, FT3,
TrT3, TSH, anti-thyroglobulin and anti-thyroid peroxidase
antibodies, as well as urinary iodine concentration (UIC)
were determined. Iodine intake was estimated with a 24 h
recall and thyroid volume was evaluated by ultrasound in 70%
of the sample. Results: Mean age was 21.7±3.5 years-old; the
TSH median value was 1.87 mIU/L, while TT4 median value
was of 9 mcg/dL. The median values for FT4 and TrT3 were
1.32 and 40.1 ng/dL, respectively. The prevalence of subclinical hypothyroidism was 2.9% (TSH>4.5 mIU/L) and 7.9%
(TSH>3.5 mIU/L). The prevalence of positive anti-thyroglobulin antibodies was 5%, whereas the prevalence of positive
anti-TPO antibodies was 5.9%. Iodine intake was estimated
in 76.8±33.8 mcg/day. Median UIC was 146 mcg/L. Thyroid
volume was 5.5±2.0 mL and the prevalence of goiter was 0%.
Conclusions: There is an adequate iodine nutrition and an
expected prevalence of thyroid function abnormalities in this
sample of Mexican women in reproductive age. According to
previous reports (Canaris G.J. et al. Arch Intern Med. 2000;
160: 526) the prevalence of thyroid disease for this age-group
was lower in our sample.
Keywords: iodine nutrition; thyroid hormones; women.
PO167 AVALIAÇÃO DA ANÁLISE COMBINADA DAS
CARACTERÍSTICAS ULTRASSONOGRÁFICAS E
CITOLÓGICAS DE NÓDULOS TIREOIDIANOS NA
DIFERENCIAÇÃO DE NÓDULOS BENIGNOS E MALIGNOS
83
Abstracts: Poster
Liberati APT1; Tomimori EK1; Silva ES2; Marui S1; Camargo RY1
1
Unidade de Tireoide do Serviço de Endocrinologia/Hospital das Clínicas
da Faculdade de Medicina/Universidade de São Paulo (HC/FMUSP;
2
Departamento de Estatística/Universidade Estadual de Maringá (UEM) Introdução: A análise das características ultrassonográficas
auxilia na identificação dos nódulos suspeitos para malignidade e na seleção dos nódulos que devem ser avaliados citologicamente. Objetivo: Verificar o papel da análise combinada
das características ultrassonográficas e citológicas na diferenciação de nódulos benignos de malignos. Pacientes e métodos: Foram analisadas as características ultrassonográficas e
citológicas de 325 nódulos submetidos à tireoidectomia no
HC/FM/USP. De acordo com as características ultrassonográficas, os nódulos foram classificados em graus I a IV (escore
1 a 4), sendo I e II benignos, III indeterminado e IV suspeito
para malignidade. Os exames citológicos foram classificados
em: benigno (escore 1), indeterminado (escore 2), suspeito
(escore 3) e maligno (escore 6). A soma dos escores ultrassonográficos e citológicos entre 2 a 4 foram considerados benignos, 5 duvidosos, 6 suspeitos e 7 a 10 malignos. Resultados:
O resultado anatomopatológico diagnosticou 141 nódulos
benignos e 184 malignos. Ao exame ultrassonográfico (US),
62 (19%) foram considerados benignos, 217 (67%) indeterminados, e 46 (14%) suspeitos para malignidade. Dos nódulos considerados benignos ao ultrassom, 85,4% confirmaram
benignidade e, dos nódulos considerados suspeitos para
malignidade, 95,6% confirmaram malignidade (p< 0,001).
Já 96% daqueles com citologia benigna confirmaram benignidade e 34% das citologias indeterminadas tiveram diagnóstico maligno. A análise combinada dos 2 métodos mostrou maior risco de malignidade nos nódulos com citologia
indeterminada que apresentavam características suspeitas
ao US e menor risco naqueles com características benignas.
Conclusão: A análise combinada das características ultrassonográficas e citológicas auxiliam a identificar os nódulos com
maior risco de malignidade.
Palavras-chave: nódulo tireoidiano; ultrassonografia; citologia.
Hyperthyroidism
PO168 THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS:
CASE REPORT
Colombo BS1; Silva MC1; Canalli MHBS1; Colombo G1
1
University Hospital Polydoro Ernani de São Thiago/Federal University of
Santa Catarina Background: Thyrotoxic Hypokalemic Periodic Paralysis
(THPP) is a hyperthyroidism complication that predominates in Asian men (20-40 years). It presents with recurrent
and transient episodes of muscle weakness (especially lower
limbs [LLs]), while sensory function is not affected. It can be
life-threatening. The diagnosis is based on history, physical
examination, hypokalemia, suppressed TSH, high free T4.
Case Report: A.H.B, 39 years-old, male, no comorbidities,
with sudden muscle weakness in LLs, just after waking up.
In the emergency service, physical examination revealed: LLs
paraparesis Grade 2, firm/not enlarged thyroid, HR 120 bpm,
BP 140/80 mmHg. Lab: K 2.6mEq/L (NR 3.5-5.1), fasting glucose (FG) 144mg/dL, TSH < 0.01 mIU/L (NR 0.35-5.5), free
T4 2.67 ng/dL (NR 0.89-1.8). After potassium replacement,
the symptoms regressed. Referred to Endocrinology for
84
hyperthyroidism. He complained of weight loss, tremors and
irritability for months. New biochemical analyses: Anti-TPO
129 IU/mL (NR< 25), TRAB 2.14 IU/mL (NR<1.75), FG
140 mg/dL, HbA1C 6.8%. Methimazole 10 mg was initiated
to control hyperthyroidism and metformin XR 1000 mg for
Diabetes. The patient experienced symptomatic improvement
(no new symptoms of paraparesis). After 2 months, thyroid
function revealed TSH 0.01 mIU/L, free T4 1.78 ng/dL, FG
103 mg/dL, HbA1c 5.5%. Discussion: The pathophysiology
of THPP is controversial (ß-adrenergic stimulation, increase
insulin resistance, compensatory hyperinsulinemia). We describe a case of THPP that can be associated with hyperthyroidism and possible hyperinsulinemia. The diagnosis should be
considered in all patients with painful muscle weakness, since
it constitutes a treatable disorder that can lead to morbidity or
mortality directly or indirectly.
Keywords: hyperthyreoidism; hypocalemia; periodic paralysis.
Hypothyroidism
PO169 THE INFLUENCE OF SUBCLINICAL
HYPOTHYROIDISM IN DEPRESSIVE SYMPTOMS AND
COGNITIVE IMPAIRMENT OF ELDERLY SUBJECTS FROM A
TERTIARY HOSPITAL
Chan IT1; Sial J1; Leu A1; Paixão Jr CM2; Vaisman M1; Silva SO1; Teixeira PFS1
1
de Janeiro (UFRJ), Universidade do Estado do Rio de Janeiro (UERJ) This study evaluated the prevalence of depressive symptoms
(DSy) and cognitive impairment in elderly subjects with subclinical hypothyroidism (SH) in comparison to euthyroidism
(EU). Methods: Patients from a cohort of a tertiary ambulatory
setting were included in this sectional study. Exclusion criteria
were: Levothyroxin use, overt hypothyroidism (TSH>10 mIU/
mL with low FT4 [0,8-1,9 ng/dL]), hyperthyroidism (TSH<
0,4 mIU/mL), hospital admission in the previous 6 months, use
of amiodarone or iodine contrasts. Subjects were analyzed in 2
groups: G1= 65-85 years (n=165) and G2 ≥ 85 years (n=61).
DSy were assessed by Geriatric Depression Scale (GDS-15)
and the screening test for cognitive impairment was the Mini
Mental State-Examination (MMSE). Cornel scale assessed
DSy when MMSE <13. Serum TSH and FT4 were obtained
from all participants. Results: DSy were present in 45.3% of
EU and 56.8% of SH group (p=0.274), however in G1, it was
more prevalent in SH (65.4% versus 46.2% in EU; p=0.049). In
G2 the prevalence did not differed between groups (EU=42.9%
versus SH=36.4%). Cornel scores were higher in SH patients
from G1 (12,3 ± 8,4) in comparison to EU (7,0 ± 4,3) from the
same group (G1); p=0.022. In G2, there were no differences in
EDG-15 or Cornel scores between SH or EU subgroups. There
was no association between cognitive impairment and SH in
the studied group, irrespective to age. Conclusions: Depressive
symptoms were associated with SH only in elderly subjects
(≤85 years-old). Cognitive impairment was not associated with
SH in the elderly.
Keywords: hypothyroidism; depression; dementia.
PO170 TIROIDITIS DE HASHIMOTO ASOCIADO A
POLINEUROPATÍA IDIOPÁTICA DESMIELINIZANTE
CRÓNICA (CIDP)
Jiménez M1; Jiménez P1; Toledo V1; Iturrieta V1
Hospital Regional Temuco, Universidad de la Frontera 1
Abstracts: Poster
18 años, varón, derivado a endocrinólogo por hipotiroidismo
grave. Anamnesis: cuadro de 5 meses de evolución, caracterizado por tetraparesia de predominio distal progresiva e
hipoestesias de manos y pies. En los últimos dos meses hubo
dificultad en la marcha. Examen físico: bradicardia 56 por
minuto, bocio difuso grado II, examen cardiopulmonar normal. Llaman la atención la arreflexia, los exámenes TSH 46
uUI/L, T4 6,7 ug /dL, T3 141 ng /mL, TPO >1000; la ecografía tiroidea: el bocio difuso heterogéneo, las pequeñas adenopatías peritiroideas reactivas, la Tiroiditis de Hashimoto.
Se inicia con levotiroxina 200 mcg/día y se deriva a neurólogo. Quien lo evalúa, destaca: cefaloparecia (-), tetraparesia
predominio distal en 4 extremidades (EESS: Proximal M5/5,
Distal M3/5; EEII Proximal M2/5, Distal 4/5M), hipoestesias
en guante y calcetín en extremidades, marcha: steppage (+),
plantares flexores y arreflexia universal. Electromiografía:
compromiso polirradículo - neural tipo desmielinizante de
cuatro extremidades; hemograma, función renal, hepática y
VIH normales; Anti ENA, Antinucleares, Anti DNA, ANCA
c y p: negativos; C3:126 ng/dL C4:22,4 ng/dL. Líquido cefalorraquídeo: Prot.Totales: 121,2 mg/dL Glucosa: 65 mg/dL
LDH:<30 U/L, cultivo (-), VDRL (-), ADA: 7,6 U/L, recuento
células leucocitos: 0/mm3, hematíes: 1500/mm3; Disociación
albumino-citológica (+), TAC cerebral: sin hallazgos patológicos. Se inicia con prednisona 80 mg/día por 4 semanas,
luego se va disminuyendo progresivamente. Evoluciona con
buena respuesta a la terapia (TSH 0,69 uUI/L, T4L 1,6 ng/
dL), recupera sensibilidad, reflejos y marcha. Actualmente, ya
pasados tres meses desde su diagnóstico, está en tratamiento
con levotiroxina 150 mcg, prednisona 5 mg/día y rehabilitación kinésica. Se comunica este caso por lo inusual de la asociación de Tiroiditis de Hashimoto y CIDP.
Palabras clave: hipotiroidismo; polineuropatía desmielinizante crónica; polineuropatía.
Genetic
PO171 MANIFESTACIONES TIROIDEAS EN EL SÍNDROME
HAMARTOMATOSO TUMORAL DEL PTEN
Faure EN1; Pastorino Casas V1; Garuti R2; Tosti R1; Lutfi RJ3 1
Complejo Médico PFA Churruca Visca; 2Complejo Médico PFA ChurrucaVisca; 3Complejo Médico PFA Churruca Visca Introducción: El Síndrome de Cowden (SC) y el Síndrome de
Bannayan-Riley-Ruvalcaba (SBRR) son expresiones fenotípicas distintas del Síndrome hamartomatoso tumoral del PTEN
(SHTP), debido a mutaciones autosómicas dominantes en la
línea germinal del gen supresor tumoral PTEN. Estas mutaciones solo se identifican en el 80% de los SC y en el 60% de
los SBRR. Las manifestaciones clínicas incluyen macrocefalia,
gangliocitoma cerebeloso, lesiones mucocutáneas hamartomatosas, pólipos intestinales, lipomas, lentiginosis en pene,
patología tiroidea y tumores malignos, principalmente de
mama y tiroides. Caso clínico: Varón de 32 años con ganglioneuromatosis intestinal, es derivado a Endocrinología para
estudio de patologías asociadas a esta entidad. Antecedentes
familiares: padre con cáncer de pulmón. Presenta signos y síntomas de hipertiroidismo; bocio multinodular; macrocefalia;
testículos de 50 mL; lesiones en mucosa oral, triquilemomas
faciales, queratosis acral y lentiginosis en pene. Laboratorio,
centellograma y captación tiroidea compatibles con hipertiroidismo por Enfermedad de Graves. Citología tiroidea:
Categoría II de Sistema Bethesda. Citología y Tg PAAF de
ganglio: negativas. TAC de cuello, tórax, abdomen y pelvis:
Bocio. Ecografía testicular: testículos aumentados de tamaño
con lipomatosis. Recibe antitiroideos previo a tiroidectomía total. Anatomía patológica: Hiperplasia multinodular
con cambios oxifílicos y tiroiditis crónica. Pendiente resultado de estudio genético. Sus dos hijos presentan macrocefalia. Conclusiones: El SHTP presenta una alta prevalencia
de enfermedades tiroideas, tales como bocio multinodular,
tiroiditis autoinmune, hipotiroidismo, hipertiroidismo y cáncer papilar y folicular. Es importante el diagnóstico precoz del
síndrome, dado el alto riesgo de que se desarrollen tumores
malignos. Se presenta este caso por la rareza del mismo.
Palabras clave: cowden; PTEN; sme hamartomatoso.
PO172 RELACIÓN DE AUTOINMUNIDAD TIROIDEA Y
CARCINOMA DIFERENCIADO DE TIROIDES
Rivadeneira S1; Gutnisky L1; Viale F1; Olstein G1; Colobraro A1; Gauna A1 1
Hospital J. M. Ramos Mejía Introducción: Es referida una presentación menos agresiva y un mejor pronóstico en pacientes con Carcinoma
Diferenciado de Tiroides (CDT) y con Enfermedad
Tiroidea Autoinmune (ETA). Objetivos: a) Evaluar antecedente de ETA clínica en CDT. b) Analizar prevalencia
de Tiroiditis Crónica o Infiltrado Linfocitario en anatomía
patológica (TC/IL). C) Comparar edad de presentación
y TNM en CDT según TC/IL y anticuerpos antitiroideos
(TAbs). Métodos: a) Se evaluaron aleatoriamente 68 pacientes con CDT. Edad x=43 años; pT1: n=27, pT2: n=16, pT3:
n=21, pT4a: n=4. b) Antecedente ETA clínica confirmado
con TAbs+: TPOAb,TGAb (Quimioluminiscencia) y/o TRAb
(Radioreceptor). c) TC/IL: infiltrado linfocitario, folículos
linfoides y cambios metaplásicos tipo Hürthle. Resultados: Antecedente ETA en 26/68 pacientes. La edad al momento
del diagnóstico de CDT fue más tardía en estos pacientes que
en aquellos sin ETA (x=47,1±12,0 vs 41,9±13,6 años, p<0.05);
9/26 con ETA tenían <45 años vs 29/44 sin ETA (p<0,01). TC/
IL en 30/68 pacientes. pT1/pT2 fue más frecuente que en los
pacientes sin TC/IL (p<0,04); pT4 presentaron 4 pacientes
con TC/IL y ninguno sin TC/IL. Entre pacientes con TC/
IL no se observaron diferencias en tamaño tumoral si TAbs
positivos o no. Nueve pacientes presentaron TAbs+ sin TC/
IL. De ellos, 1/9 fue pT1 vs 9/20 pT1 en TAbs+ con TC/IL+
(p<0,04). Conclusiones: En esta población de CDT, el 38%
tuvo antecedente de ETA. La edad, al momento del diagnóstico de CDT, fue más tardía. La presencia de TC/IL se asoció
con menor tamaño tumoral al diagnóstico, independientemente de los anticuerpos. La presencia de anticuerpos sin
TC/IL se asoció con menor prevalencia de tumores chicos.
Palabras clave: autoinmunidad tiroidea; cáncer diferenciado
de tiroides; tiroiditis crónica.
Thyroid Nodule
PO173 PERCUTANEOUS LASER ABLATION IN BENIGN
THYROID NODULES: FIRST BRAZILIAN EXPERIENCE
Andreoni DM1; Garcia RG2; Janovsky CPS1; Mendes GF2; Ikejiri ES1;
Lucio JFF2; Hidal JT1; Francisco Neto MJ2; Maciel RMB1 1
Universidade Federal de São Paulo (UNIFESP); 2Hospital Israelita Albert
Einstein
85
Abstracts: Poster
Several trials have demonstrated that laser ablation (LA) is a
safe and good treatment for the shrinkage of benign thyroid
nodules. In Brazil, this modality of treatment has not yet been
implemented. Objectives: As our center was the pioneer in
Brazil to access this type of technology, the aim of this study
was to determine the implementation of interstitial laser
ablation technique to the treatment of benign thyroid nodules, as an alternative to conventional surgical treatment in
Brazil. We also assessed its effect on nodule volume, thyroid
function and nodule – related symptoms referred by the
patient. Methods: Thirty euthyroid and thyroid antibodies
negative patients with benign solitary or dominant nodule
were recruited from a Thyroid Disease Clinic. All patients had
treatment indication due to compressive symptoms, aesthetic disturbances, large size and/or surgery contraindication.
The clinical and laboratory evaluation was performed before
the procedure and periodically 1 week, 3, 6, 9 and 12 months
after. Results: We have already evaluated 30 patients, with a
total of 31 nodules submitted to laser ablation. The volumetric
reduction of the nodule was approximately 60% after 9 months
of the procedure. No statistical significance was observed on
thyroid function and antibodies levels. As expected, there was
a peak on the level of thyroglobulin after the procedure due
to tissue destruction (p<0.0001). There were no adverse effects
referred by the patients. Conclusion: The first Brazilian experience on percutaneous laser ablation was a great success. Our
initial results are in congruence with the literature.
Keywords: laser ablation; thyroid nodule; benign thyroid
nodule.
PO174 DOENÇAS DA TIREOIDE: UM ALERTA CONTRA A
NEGLIGÊNCIA NA PREVENÇÃO, NO ACOMPANHAMENTO E
NO TRATAMENTO DAS AFECÇÕES PREVALENTES
Torres FF1; Brasileiro ES2; Arruda CCC2; Silva KF2; Leite DSA2; Bezerra
CSM2; Cruz NA2; Sampaio RAAF2; Guedes LSM2; Filho PCM2; Façanha CFS3; Forti AC2
1
Universidade Federal do Ceará, Sociedade Brasileira de Endocrinologia –
Regional Ceará; 2Faculdade de Medicina da Universidade Federal do Ceará;
3
Sociedade Brasileira de Endocrinologia – Regional Ceará
Introdução: Patologias tireoidianas, entre doenças nodulares
e disfunções hormonais, afetam aproximadamente 10% da
população mundial, comprometendo a qualidade de vida e
podendo levar ao óbito. A maioria tem excelente prognóstico
quando diagnosticadas precocemente e adequadamente tratadas, porém o acesso a serviços especializados nem sempre é
possível. Objetivos: Identificar sinais e sintomas característicos
das doenças tireoidianas, bem como diagnosticá-las e tratá-las
precocemente. Materiais e métodos: A Sociedade Brasileira
de Endocrinologia e Metabologia, a Sociedade Brasileira de
Cirurgia de Cabeça e Pescoço e a Liga de Endocrinologia
da UFC realizaram, no dia 26 de maio de 2012, a campanha
“Examine sua tireoide”. Foram abordadas 493 pessoas com
questionário sobre as principais manifestações clínicas das
afecções tireoidianas, além de palpação da tireoide. Foram
feitas solicitações de TSH, ultrassonografia (USG) de tireoide
e punção aspirativa por agulha fina (PAAF), e houve encaminhamento para posterior seguimento. Resultados: Dentre os
60 pacientes que retornaram ao seguimento, a idade média
foi 46,66 anos; 31,9% tiveram valores de TSH alterados, e 75%
tiveram USG alterada, evidenciando bócio nodular (48,3%),
bócio difuso (16,7%) e tireoidite (10%). Em 23,4%, foi solicitada PAAF. Cinquenta por cento foram encaminhados para
86
acompanhamento, 25% iniciaram tratamento farmacológico,
16,7% foram encaminhados ao cirurgião e 10% receberam
alta. Conclusão: Foi obtido maior índice de rastreamento de
nódulos tireoidianos e de alteração patológica de TSH que a
média vista em estudos epidemiológicos recentes. Esse valor
se deve ao amplo anúncio da campanha em meios de comunicação, direcionando-se a quem tinha manifestações clínicas
tireoidianas, demonstrando o amplo benefício que a campanha, com seguimento, traz à população.
Palavras-chave: diagnóstico precoce; rastreamento; medicina preventiva.
PO175 PREVALENCIA DE BOCIO Y SU RELACIÓN
CON PARÁMETROS BIOQUÍMICOS EN PACIENTES
ACROMEGÁLICOS
Alfieri A1; Giacoia E1; Cabrera S2; Magat P2; Moratto E2; Corino M2 1
Hospital Nacional A. Posadas; 2Hospital Posadas Objetivo: Establecer la prevalencia de bocio en acromegalia y relacionarlo con parámetros bioquímicos. Material y
Método: Se analizó, retrospectivamente, 42 acromegálicos
(junio 2000-mayo 2012). Se analizó clínica, TTOG/GH, IGF1
y adenoma pituitario por TC o RMN. Se incluyeron n=28
pacientes. Consideramos: edad, sexo, presencia de bocio
(por palpación o ecografía), niveles de IGF1, de acuerdo
con edad y sexo, de GH y de T4L por QML Análisis estadístico Tests: Student (media±DS) para distribución normal,
Mann Whitney (mediana y rango) para distribución anormal
y Fisher para variables categóricas. Se consideró estadísticamente significativa una p< 0,05. Se realizó una regresión
logística para IGF1 ajustada a edad y sexo. Resultados: 15 de
28 pacientes (53,5%) presentaron bocio (7 palpación y 8 ecografía), 7/15 46% nodulares y 8/15 difusos. 2 pacientes (12%)
hipertiroideos. No se observó diferencias por sexo. La relación bocio e IGF1 fue estadísticamente significativa (p=0,02).
El bocio no correlacionó con TSH ni con GH. En la regresión
logística sobre IGF1, se observó que para un incremento de
100 unidades de IGF1 la probabilidad de bocio aumenta un
49%. Conclusiones: La prevalencia de bocio en pacientes
con acromegalia fue del 53,5%, mientras que para la población general es del 6%. Los pacientes con bocio presentaban
niveles más elevados de IGF1. No se registraron diferencias al
analizar sexo y niveles de GH ni de TSH.
Palabras clave: bocio; acromegalia; IGF 1.
PO176 ACUTE SUPURATIVE THYROIDITIS BY E. COLI: A
CASE REPORT
Noriega VH1; Huachin MK1; Jara J1; Baca R1 1
Hospital Nacional Cayetano Heredia Background: Acute suppurative thyroiditis is a rare disease.
The most common cause is bacterial infection, although fungal infections, parasites or mycobacteria have been reported. Objectives: To report a case of a patient with suppurative thyroiditis caused by Escherichia coli. Methods: Review
of medical records. Results: We report a case of a 50-yearold woman with a history of type 2 diabetes associated with
long-term complications and hypertension. She refers anterior cervical tumor, dysphagia, weakness and malaise without
fever. Two days before hospitalization developed dysphonia.
Physical examination evidence non tender goiter without
phlogosis.The leukocyte count was 19,600/mm3, hemoglobin
10 gr/dL, C-reactive protein 244 mg/L, creatinine 1.34 mg/dL,
Abstracts: Poster
urea 68.8 mg/dL, glucose 213 mg/dL. The thyroid ultrasound
shows possibility of abscess. Ceftriaxone 2 g QD starts, clindamycin 900 mg TID, tramadol 50 mg TID EV, NPH insulin
and regular insulin SC. The cervical CT scan shows an abscess
with necrosis and gas in the left thyroid lobe. Was scheduled for
thyroidectomy and drainage of abscess yielding approximately
50 cc of pus. E. coli was obtained on drainage culture. The same
germ is isolated in 2 successive urocultures. The evolution of
the patient was favorable. Conclusion: Poorly controlled diabetes may be cause of this rare condition. In this case, the primary focus was the urinary infection undertreated.
Keywords: supurative thyroiditis; acute thyroiditis; diabetes
mellitus.
PO177 INGESTÃO CRÔNICA DE CANELA REGULA A
EXPRESSÃO DE GENES ENVOLVIDOS NO METABOLISMO
DE COLESTEROL EM RATOS HIPOTIREÓIDEOS
Lopes BP1; Gaique TG2; Souza LL1; Paula GSM1; Pazos-Moura CC1;
Oliveira KJ2
1
Universidade Federal do Rio de Janeiro (UFRJ);2 Universidade Federal
Fluminense (UFF) Introdução: A ingestão de canela exerce efeitos benéficos
sobre perfil lipídico de modelos dislipidêmicos, porém dados
recentes de nosso grupo demonstram que ratos hipotireóideos
tratados com canela em pó apresentam aumento de colesterol total e LDL. Objetivo: Investigar mecanismos associados
ao efeito hipercolesterolêmico da canela em ratos hipotireóideos. Métodos: Ratos machos Wistar adultos foram divididos
em 3 grupos: eutireóideo (EU); hipotireóideo (HIPO – 0,03%
de metimazol na água de beber por 21 dias) e hipotireóideo
+ canela (HIPO-CAN – 7g canela em pó/Kg ração padrão
por 25 dias). Metimazol foi mantido durante o tratamento
com canela. A expressão gênica hepática de receptores para
hormônio tireoidiano (TRa1 e TRb1), proteína ligadora do
elemento regulado por esteróis (SREBP2), receptor de LDL
(LDLR) e colesterol 7-a-hidroxilase (CYP7A1) foram analisados por reação em cadeia pela polimerase (polymerase chain
reaction, PCR) em tempo real. Resultados: As expressões do
SREBP2 e seu gene-alvo LDLR, que se encontram menores
no HIPO, foram maiores no HIPO-CAN (75% e 153%, respectivamente, p< 0,01 versus HIPO). A expressão do TRa,
que se encontra maior no HIPO, foi reduzida no HIPO-CAN
(-42%, p< 0,05 versus HIPO). Não houve alteração na expressão do TRb1 e CYP7A1 entre os grupos. Conclusão: Apesar
da ingestão de canela em pó agravar a hipercolesterolemia
nos ratos hipotireóideos, observamos maior expressão gênica
de SREBP2 e LDLR, genes envolvidos na via de captação
hepática de colesterol. É possível que a indução de SREBP2
possa favorecer de forma mais expressiva vias de biossíntese
de colesterol, resultando no agravamento da hipercolesterolemia observada nos ratos hipotireóideos tratados com canela.
Palavras-chave: canela; colesterol; SREBP2.
Hypothyroidism
PO178 DIPHENYL DISELENIDE REGULATES EXPRESSION
OF ANTIOXIDANT GENES IN METHIMAZOLE-INDUCED
HYPOTHYROID FEMALE RATS
Dias GRM1; Golombieski R1; Nogueira CW1; Vargas NBV1 1
Universidade Federal de Santa Maria (UFSM) Earlier we have demonstrated that diphenyl diselenide
(PhSe)2 an organic selenium compound that possesses antioxidant and neuroprotective properties caused an improvement of deficit cognitive in hypothyroid female rat (Dias et
al., 2012). This study was performed to clarify the effects of
hypothyroidism induced by methimazole (MTZ) on antioxidant enzyme activities and on expression of antioxidant
genes, and to investigate the potential use of (PhSe)2 to regulate these parameters. Female rats were exposed to MTZ
0.02 g/100 mL in the drinking water and (PhSe)2 5 ppm
supplementation in the diet for 3 months. At the end, activity of antioxidant enzymes and mRNA levels of antioxidant
genes were performed in cortex, hippocampus and striatum.
Hypothyroidism was confirmed by a significant decrease in
thyroid hormone levels. Activities of antioxidant enzymes
demonstrated a significant inhibition of catalase (CAT) by
MTZ exposure and Se intake in striatum and a significant
increase in superoxide dismutase (SOD) in hippocampus of
Diet-Se+MTZ group. Glutathione peroxidase (GPx) activity
was not altered. Analysis of mRNA levels of antioxidant enzymes demonstrated an up-regulation of CAT, SOD-1, SOD-2,
SOD-3, GPx-1, GPx-4, TrxR-1, TrxR-2 by MTZ exposure and
a return to basal values when (PhSe)2 supplementation was
associated to hypothyroid condition. This up-regulation of
mRNA levels of antioxidant enzymes was associated to Nrf-2
antioxidant signaling since positive correlation was found in
cortex and hippocampus. (PhSe)2 supplementation reversed
these effects. In conclusion this study was able to demonstrate
that (PhSe)2 supplementation in the diet can improve signaling related to antioxidant pathways in hypothyroidism.
Keywords: diphenyl diselenide; hypothyroidism; antioxidant
enzymes.
PO179 ANTIDEPRESSANT-LIKE EFFECT OF DIPHENYL
DISELENIDE SUPPLEMENTATION IN THE EXPERIMENTAL
HYPOTHYROIDISM INDUCED BY METHIMAZOLE
Dias GRM1; Almeida TM1; Nogueira CW1; Barbosa NBV1
1
Universidade Federal de Santa Maria (UFSM) Evidences from literature demonstrate that thyroid dysfunction is associated with psychiatry disorders, such as depression, anxiety and cognitive deficit (Van Boxtel et al., 2004;
Guimarães et al., 2009). This study investigated the depressivelike behavior in a model of hypothyroidism induced by methimazole (MTZ), and the antidepressant-like effect of diphenyl
diselenide supplementation in the diet with the main objective of ameliorating this disorder. Additionaly we investigated
TBARS, ROS and NP-SH levels in cortex, hippocampus and
striatum; and MAO activity in total brain. Female rats received MTZ 20 mg/100 mL in the drinking water for 30 days
and were evaluated in open-field and forced swimming tests
(FST). FST evidenced a depressive-like behavior represented
by a significant increase in immobility time when compared
to control group. Then rats were re-divided randomly into 4
groups: control, MTZ, diet-Se and MTZ+diet-Se and re-evaluated in open-field and FST tests monthly. Antidepressantlike effect of diphenyl diselenide was evident in the 3 evaluations realized without altering the locomotor performance
in open-field test. Levels of thyroid hormones remained low
in diphenyl diselenide group. TBARS and ROS levels were
increased in hippocampus of MTZ group and restored to
control levels by diphenyl diselenide. NP-SH levels were no
87
Abstracts: Poster
altered. MAO B activity was decreased by MTZ administration and also restored by diphenyl diselenide. Taken together,
these results indicate that hypothyroidism induced by methimazole triggers a depressive-like behavior in female rats and
that diphenyl diselenide was able to reverse this disorder
mainly due its well recognized antioxidant properties and
antidepressant-like effect.
Keywords: diphenyl diselenide; hypothyroidism; depression.
PO180 DIPHENYL DISELENIDE SUPPLEMENTATION
AFFECTS BIOCHEMICAL PARAMETERS IN THE
EXPERIMENTAL HYPOTHYROIDISM INDUCED BY
METHIMAZOLE
Dias GRM1; Dobrachinski F1; Bridi JC1; Portella R 1; Carvalho NR1;
Nogueira CW1; Barbosa NBV1 1
Universidade Federal de Santa Maria (UFSM) Selenium (Se) is a trace element essential to thyroid functions. The present study investigated the effect of diphenil
diselenide supplementation on biochemical parameters in
the experimental hypothyroidism induced by methimazole
in female rats, since this organoselenium compound possess antioxidant and neuroprotective properties (Nogueira
& Rocha, 2010). Experimental groups were control, hypothyroid, diet-Se and diet-Se+hypothyroid and treatments
were maintained for 5 and 14 weeks. Biochemical parameters analyzed were lipid peroxidation, ROS and non protein
thiols levels and Na+, K+-ATPase, acetylcholinesterase and
d-ALA-D activities from different tissues. Hypothyroidism
was efficiently induced because tT3 and tT4 levels were
significantly reduced in hypothyroid groups. Hypothyroid
groups presented an increase in lipid peroxidation in cerebral
structures, which was reversed by diphenyl diselenide supplementation. ROS determination in cerebral structures also
presented a significant inhibition by diphenyl diselenide supplementation. Non protein thiols levels determination was
increased in cerebral structures, such hippocampus and striatum in treatment of 5 weeks and in cortex in treatment of 14
weeks. Na+, K+-ATPase, acetylcholinesterase and d-ALA-D
activities were altered in both treatments, but without signs
of toxicity of diphenyl diselenide supplementation. Liver and
kidneys did not exhibit lipid peroxidation or ROS enhanced.
In this way, we suggested that oxidative stress parameters
were improved by diphenyl diselenide supplementation and
enzymatic activities evaluated were altered according to brain
region studied. Diphenyl diselenide supplementation can be
a potential agent therapeutic in hypothyroidism induced by
methimazole.
Keywords: diphenyl diselenide; oxidative stress; hypothyroidism.
PO181 EXPRESSION OF CASPASES AND BCL-2 FAMILY
GENES UNDER HYPOTHYROIDISM: MODULATION BY
DIETARY DIPHENYL DISELENIDE
Dias GRM1; Golombieski R1; Nogueira CW1; Barbosa NBV1
1
Universidade Federal de Santa Maria (UFSM) This study was aimed to investigate the potential use of dietary diphenyl diselenide in regulating caspases (3, 6, and 9)
and Bcl-2 family genes expression under hypothyroidism
condition. Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ) at 20 mg/100 mL
in the drinking water, during 3 months. Concomitantly,
88
MTZ-induced hypothyroid rats were fed or not with a diet
supplemented with diphenyl diselenide at 5 ppm. At the end of
trials, mRNA levels of caspases (3, 6, and 9) and Bcl-2 family
genes (BAX, BAD, BAK, Bcl-2, and Bcl-XL) were determined
in cortex, hippocampus and striatum by qPCR. Concerning to
genes expression, mRNA expression of caspase 3, 6 and 9 were
significantly increased by MTZ exposure in cortex and hippocampus. Diet-Se intake was able to reverse this effect. However,
mRNA expressions of caspases were not altered in striatum. It
was also observed that hypothyroidism caused a marked upregulation on mRNA expression of pro-apoptotic members of
Bcl-2 family (BAD, BAK, and BAX) in cortex and hippocampus. Diet-Se intake reversed this MTZ exposure effect. Besides
Diet-Se intake significantly increased mRNA expression of antiapoptotic genes Bcl-XL and Bcl-2 in cortex. However, mRNA
expressions of Bcl-2 family genes were not altered in striatum.
This study was able to demonstrate that hypothyroidism stimulate apoptosis to augment caspases and pro-apoptotic Bcl-2
family members’ levels. As demonstrated diphenyl diselenide, a
simple organic selenium compound can be an interesting pharmacological approach to improve these parameters.
Keywords: diphenyl diselenide; hypothyroidism; apoptosis.
Iodine Deficiency
PO182 TSH NEONATAL A LO LARGO DE 10 AÑOS DE
PESQUISA DE HIPOTIROIDISMO CONGÉNITO EN UN
HOSPITAL DE LA CIUDAD DE BUENOS AIRES: VARIACIONES
DE UN INDICADOR DE DEFICENCIA DE IODO
Junco M1; Odriozola A1; López M1; Silva Croome MC1; Gauna A1; Glikman P1 1
División de Endocrinología, Hospital “J. M. Ramos Mejía” Introducción: WHO, UNICEF y ICCIDD propusieron TSH
neonatal como uno de los indicadores del grado de déficit de
Iodo (DDI) y su control.1,2 La incidencia de TSH>5 mUI/L
en sangre entera es <3% en ausencia de DDI, mientras que
(3-19,9), (20-39,9) y >40% indican DDI leve, moderado o
severo, respectivamente. Objetivo: Determinar en nuestra población la incidencia de TSH neonatal >5 mUI/L
y su variación durante un período de 10 años. Métodos:
Evaluamos TSH (mUI/L de sangre entera) en 19.673 muestras de sangre seca sobre papel de filtro S&S 903, extraídas entre el tercer y el séptico de edad, de neonatos de los
Hospitales Ramos Mejía y Penna, Gobierno de la Ciudad de
Buenos Aires, período 1/1/2002-31/12/2011. TSH se midió por
método inmunofluorométrico DELFIA (PerkinElmer), sensibilidad analítica: 2 mU/L. Estadística: análisis de regresión.
Programa InStat. Resultados: Un 6,1% de las muestras, en
la población total, presentó TSH>5 mUI/L. Los datos anuales correspondientes fueron (Año/Nº de muestras/%TSH>5):
2002/1661/9,3; 2003/1616/7,1; 2004/2066/10,6; 2005/1513/8,9;
2006/1838/6,0; 2007/2290/5,5; 2008/2444/3,1; 2009/2131/4,6;
2010/1752/5,2; 2011/2352/3,5. La disminución del % con
el tiempo fue lineal y significativa (y=-0,6873+1385,4;
R2=0,6749; p=0,0036). Conclusiones: a) La incidencia de
TSH neonatal >5 mUI/L es compatible con el déficit leve
de Iodo en la población total. b) Del 2002 a 2011 hubo una
disminución significativa en la incidencia de TSH>5 mUI/L,
manteniéndose en rango de déficit leve. c) Esta disminución
anual podría deberse a cambios en la composición étnica o a
la ingesta de Iodo de la población estudiada. Abstracts: Poster
Bibliografía: 1. WHO/NUT/94.6 Ed. World Health Organization, Geneva,1994, pp1-55. 2. Delange F. Thyroid 1998, 8(12); 1185-92.
Palabras clave: Neonatal TSH; Iodine deficiency indicator;
Congenital Hipothyroidism screening.
PO183 THYROID AUTOIMMUNITY IN THE CURRENT IODINE
ENVIRONMENT IN CHILDREN AND ADOLESCENTS IN SÃO
PAULO, BRAZIL
Miranda DMC1; Masson JN1; Tomimori EK1; Monte O1; Catarino RM2;
Santos RTM2; Toyoda S3; Marone MMS3
1
Faculdade de Ciências Médicas da Santa Casa de São Paulo; 2Instituto Adolfo
Lutz; 3Irmandade Santa Casa de Misericórdia de São Paulo Background: A strong genetic background and environmental influences are believed to be involved in thyroid autoimmunity. The continuous iodine prophylaxis and the increased
iodine intake may induce thyroid autoimmunity. One explanation is that enhanced iodine intake increases the antigenicity of thyroglobulin through the incorporation of iodine
into its molecule and the formation of iodinated thyroglobulin epitopes. Objective: The aim of this study was to determine the frequency of thyroid autoimmunity in children and
adolescents and to examine the relationship between iodine
and Hashimoto’s thyroiditis. Methods: Anti-TPO and antithyroglobulin Ab, TSH, free thyroxine and urinary iodine
were determined in 116 children and adolescents, aged 7-14
years-old. Thyroid ultrasonography was performed in all participants and a sample of urine was collected from all of them.
Autoimmune thyroiditis was diagnosed by positive serum
anti-TPO and/or anti-thyroglobulin or when hypoechogenicity was detected by ultrasonography. Results: Median urinary iodine was 170 mg/L. The prevalence of positive antiTPO and anti-Thyroglobulin was 3.4% and 2.5% respectively.
The prevalence of autoimmune thyroiditis was 4.2%. The
median urinary iodine excretion was determined as 167 mg/L
in the autoimmune thyroiditis group and 170 mg/L in normal
children. Conclusion: The iodine intake in children and adolescents in our city is optimal, and our data demonstrates that
urinary iodine excretion was the same in the autoimmune
thyroiditis group and normal children and the prevalence of
AT is the same in both groups.
Keywords: iodine; autoimmunity; children.
PO184 NORMATIZAÇÃO DA VOLUMETRIA SONOGRÁFICA
DA GLÂNDULA TIREOIDE NO PERÍODO NEONATAL
Freire R1; Monte O1; Catarino RM2; Mattos Jr HS3; Fagundes LB3;
Santos LWR3; Sterza T4; Liberato MM3; Pereira KCC4; Rocha T4;
Pereira A5; Cintra T5; Hegner C5; Lube D5; Murad M6; Casini AF6;
Tomimori EK1
1
Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP);
2
Instituto Adolfo Lutz; 3 Laboratório São Marcos, Vila Velha/ES; 4 Hospital
Universitário Cassiano Antônio de Moraes/Universidade Federal do Espírito
Santo (HUCAM/UFES); 5 Serviço de Referência em Triagem Neonatal do
Espírito Santo/Associação de Pais e Amigos dos Excepcionais do Espírito
Santo (SRTNES/APAE/ES); 6 Universidade de Vila Velha (UVV) Introdução: A ultrassonografia (US) da tireoide na triagem
do hipotireoidismo congênito (HC) é subutilizada pela dificuldade de execução e ausência de referências, no Brasil, do
volume da tireoide (VT) no período neonatal. O índice Th/Tr
ou de Yasumoto consegue estimar o VT em neonatos (RN).
Objetivos: Normatizar o VT e índice de Yasumoto. Métodos:
Estudo transversal prospectivo, com US de tireoide em tempo
real de 125 RN a termo. Validamos o eutireoidismo e iodossuficiência com: TSH filtro, TSH soro, T4 livre (FT4), tireoglobulina (Tg), ATPO, TgAb, TRAb e iodúria em amostra casual
de urina. Resultados: A média ± SD e intervalo da média ± 2
SD do VT com a constaste p/6 foi: 0,99 ± 0,27 mL e 0,45 a 1,53
mL e com fator 0,479 foi: 0,91 ± 0,25 mL e 0,41 a 1,41 mL. O
intervalo da média ± 2 SD do índice de Yasumoto foi de 1,71
a 2,87. A mediana do TSH filtro, TSH soro, FT4 e da Tg foi:
1,39 mgIU/mL, 4,29 mgIU/mL, 1,97 ng/dL, e 79,65 ng/mL. A
média ± SD da iodúria foi: 299,20 ± 72,20 mg/L. Conclusões:
O índice de Yasumoto de 1,7-2,9 constitui parâmetro simples
para estimar o VT na triagem neonatal do HC.
Palavras-chave: ultrassonografia; tireoide; neonatos.
PO185 FUNCTIONAL CHARACTERIZATION
OF HUMAN ECTOPIC THYROID TISSUE WITH
IMMUNOHISTOCHEMISTRY
Camargo RY1; Kanamura CT2; Sodre AK1; Nogueira CR3; Cerutti JM4;
Iosrcansky S5; Friguglietti CU6; Tincani AJ7; Medeiros-Neto G1;
Rubio IGS8
1
Thyroid Unit/Cellular and Molecular Endocrine Laboratory, LIM-25,
Faculdade de Medicina da Universidade de São Paulo (FM/USP); 2Adolfo Lutz
Institute/São Paulo Public Health Service; 3Department of Internal Medicine/
Botucatu School of Medicine/University of São Paulo State (UNESP); 4Genetic
Bases of Thyroid Tumors Laboratory/Division of Genetics and Division of
Endocrinology/Universidade Federal de São Paulo (UNIFESP); 5Servicio de
Endocrinología/Hospital de Pediatría Dr Juan Garrahan; 6Head and Neck
Surgery of Santa Catarina Hospital; 7Head and Neck Service/Department of
Surgery/Faculty of Medical Sciences/University of Campinas (UNICAMP);
8
Department of Biological Sciences, Federal University of São Paulo
(UNIFESP)
Background: Abnormal migration of the thyroid gland
during embryogenesis results in ectopia, with a spectrum
of thyroid migrational defects and function (from severe
hypothyroidism to euthyroidism). Objective: Functional
characterize the human ectopic thyroid tissue through examination of specific thyroid proteins by immunohistochemistry. Methods: We included 7 ectopic paraffin-samples and
antibodies against thyroperoxidase (TPO), I/Na-symporter
(NIS), TSH-receptor (TSHR), thyroglobulin (TG) and
NKX2.1 and PAX-8. Results: Anatomopathological findings
of 6 samples (2-7) were compatible with colloid goiter with
areas of macrofollicles, lymphocytary infiltrate and/or hyperplasia. Sample1 had microfollicules and normal size follicles
with linphocitary infiltrate and hyperplasia. TG and TPO
staining pattern in ectopia was similar to normal tissue. All
samples showed diffuse cytoplasmic TSHR staining; in normal thyroid its distribution is 80-90% cytoplasmic. NKX2.1
immunoreactivity was negative in 2 samples (2, 7); areas with
nuclear intense positivity (as normal control) and negative
staining were observed in the others. In 6 samples nuclear
PAX-8 staining was similar to normal tissue. In samples 3,
4, 5, 6 and in hyperplastic areas positivity was stronger than
normal tissue; however, negative areas were also detected.
NIS basal membrane localization was detected in few cells of
4 samples (2, 3, 4, and 5) as in normal control; week cytoplasmic staining was observed in the others. Conclusions: The
non-homogeneuous TTF-1 and PAX-8 expression pattern
observed suggests the presence of active and depressed active
follicle in ectopic tissue. The expression and localization of
specific thyroid proteins in most of the samples, similar to
normal tissue, may explain the ability of the ectopic thyroid
to synthetize thyroid hormones for a period of time at least.
89
Abstracts: Poster
Support: Fundação de Apoio à Pesquisa do Estado de São
Paulo (FAPESP).
Keywords: ectopic thyroid; congenital hypothyroidism; gene
expression.
PO186 TRATAMIENTO INADECUADO DE LA ENFERMEDAD
DE GRAVES DURANTE EL EMBARAZO. HIPOTIROIDISMO
CENTRAL: REPERCUSIÓN FETAL Y NEONATAL POCO
DIFUNDIDA
Alcaraz G1; Stivel M1; Abalovich M1; Vázquez A1; Calabrese C1;
Gutiérrez S1
1
División de Endocrinología, HOSPITAL DURAND Introducción: Madres con hipertiroidismo no controlado
pueden dar origen a hijos con afectación hipofisaria, con una
prevalencia similar a la tirotoxicosis neonatal. Objetivos:
Detectar hipotiroidismo central [HC] en hijos de madres
hipertiroideas, inadecuadamente tratadas durante el embarazo. Métodos: Se evaluó: a) función tiroidea materna al
momento de la consulta y luego del tratamiento con metimazol; b) función tiroidea fetal/neonatal en sangre de cordón,
y posteriormente, de acuerdo a la evolución. Diagnóstico de
HC: T4 < 8 mcg/dL -T4L < 0,9 ng/dL y TSH inapropiadamente normal. Resultados: 8 madres con hipertiroidismo
inadecuadamente tratado tuvieron hijos con HC. El diagnóstico de hipertiroidismo se realizó preembarazo en 5/8. El
eutiroidismo se alcanzó en la semana 25 en 1/8; entre 30 y 35,
en 4/8 y no se logró en 3/8. Los partos fueron a término; 5/8
RN presentaron bajo peso y solo 1 edad ósea avanzada. Las
determinaciones en cordón orientaron el diagnóstico de HC
en 5/8 RN, que fue confirmado entre los 2 y los 120 días de
vida. Cuatro RN presentaron fase de hipertiroidismo neonatal
transitorio por pasaje de TRAb maternos y recibieron metimazol hasta negativizar TRAb. Durante la Post-suspensión del
metimazol se continuó con parámetros de HC y se requirió
LT4. Conclusiones: Los hijos de madres con la Enfermedad
de Graves, inadecuadamente tratada, pueden presentar hipotiroidismo central transitorio por excesivo pasaje de hormonas tiroideas maternas que generan un ambiente de hipertiroxinemia fetal con inhibición del eje hipotálamo-hipofisario.
Para prevenir el HC es necesario un temprano diagnóstico y
un adecuado tratamiento del hipertiroidismo materno, por
lo cual esta entidad aporta un argumento más en favor del
screening de función tiroidea durante la gestación.
Palabras clave: Enfermedad de Graves y Embarazo;
Hipotiroidismo central; hipertiroidismo neonatal.
PO187 CLINICAL ASPECTS OF FAMILIAL FORMS OF
CONGENITAL HYPOTHYROIDISM
Jesus MS1; Oliveira TL2; Strappa GBS1; Pereira MMA1; Bello AA3;
Fernandes VM1; Boa Sorte TRSA3; Ramos HE1 1
Departamento de Biorregulação/Instituto de Ciências da Saúde/ Universidade
Federal da Bahia (ICS/UFBA);2Pós-Graduação em Biotecnologia em Saúde e
Medicina Investigativa Centro de Pesquisa Gonçalo Moniz/Fundação Osvaldo
Cruz (FIOCRUZ)/BA; 3Escola Bahiana de Medicina e Saúde Pública Background: The familial clustering of Congenital
Hypothyroidism (CH) has been described and suggests genetic involvement, representing 2% of all cases. Objectives:
Describe the clinical characteristics of familial forms of CH
90
identified from the beginning of the neonatal screening program in Bahia (1992-2012). Methods: Multiplex families (i.e.
with at least 2 affected members) were studied. Medical records
analysis and thyroid ultrasound were performed. We selected
a total of 87 patients belonging to 36 families with a positive
history for CH associated with either CH or Hypothyroidism
of unknown etiology. Results: Thirty-three patients with
a confirmed positive family history of CH belonging to 12
families were identified. Most cases were seen in families with
2 affected members (n=20). Both horizontal (n=9) and vertical (n=3) transmissions were observed. There were 9 families
with affected siblings and 1 with affected parents and offspring. Eight families had more distant relationships, i.e. cousins in 5 families and other relatives in 3. Thyroid phenotype
was: gland in situ (n=6), hypoplasia (n=1), agenesis (n=1),
goiter (n=2) and unknown (n=2). Extrathyroidal congenital
malformations were described in 67%. Conclusion: Familial
cases represent the minority of cases but are unexpectedly
high in proportion and have higher incidence of extrathyroidal malformations.
Keywords: congenital hypothroidism; familial disorder;
hypothyroidism.
PO188 REPERCUSSIONS OF TSH CUTOFF LEVEL TO
6 MU/L IN NEONATAL SCREENING FOR CONGENITAL
HYPOTHYROIDISM IN SANTA CATARINA: PRELIMINARY
RESULTS
Nascimento ML1; Dornbusch P2; Ohira M2; Simoni G1; Cechinel E1;
Linhares RMM1; Silva PCA1
1
Hospital Infantil Joana de Gusmão;2Universidade Federal de Santa Catarina
(UFSC)
Objective: This study assessed the implications of changing
the cutoff level of TSH from 10 to 6 mU/L. Methods: The
study population was constituted of 74.123 children screened
for Congenital Hypothyroidism by the National Screening
Program in Santa Catarina, from March 2011 February 2012.
The TSH cut-off level was 6 mU/L. If TSH was between 6 and
10 mU/L a second sample was collected. If TSH>6 mU/L in
this second sample, the child was sent for medical evaluation. Results: Four hundred thirty-five children were recalled for presenting TSH between 6 and 10 mU/L in the first
sampling, 28 remained TSH > 6mU/L in the second sampling. Among these, 15 were diagnosed as dyshormonogenesis or transient, 2 ectopic thyroids and 1 thyroid hypoplasia. Conclusion: Reducing the TSH cut-off level from 10 to 6
mU/L, reduces the number of false negatives, increasing the
test sensitivity, but increases the number of false positives and
recalls.
Keywords: congenital hypothyroidism; screening; cut-off level.
PO189 DISCORDANCE OF TWINS FOR CONGENITAL
HYPOTHYROIDISM IN 3 OF 4 IDENTIFIED PAIRS:
IMPLICATIONS FOR NONINHERITABLE POSTZYGOTIC
EVENTS
Strappa GBS1; Oliveira TL2; Jesus MS1; Pereira MMA1;
Medeiros MFS1; Boa Sorte TRSA3; Ramos HE1
1
Departamento de Biorregulação/Instituto de Ciências da Saúde/Universidade
Federal da Bahia (UFBA);2Pós-Graduação em Biotecnologia em Saúde
e Medicina Investigativa Centro de Pesquisa Gonçalo Moniz/Fundação
Osvaldo Cruz (FIOCRUZ)/BA;3Escola Bahiana de Medicina e Saúde Pública,
Associação de Pais e Amigos dos Excepcionais de Salvador (APAE)/BA Background: There is an increased incidence of congenital
malformations in monozygotic twins. Previous few studies
Abstracts: Poster
have showed discordance of twins for thyroid dysgenesis in
large congenital hypothyroidism (CH) cohorts. However,
due its curiosity value, preferential reporting of those cases
might exist. Objectives: To describe the clinical characteristics of 4 pairs of twins, which at least 1 patient had confirmed
CH identified from the beginning of the neonatal screening
program in Bahia (1992-2012). Methods: We undertook
a systematic search for twins in the computerized database
maintained by a large CH screening program conducted by
APAE in Salvador, Bahia, Brazil. The findings in these index
cases prompted a retrospective review of medical records.
Assessment of zygosity was tested by DNA analysis. Results:
Four pairs of twins were found within 5 patients presenting
CH. Three pairs were discordant with 1 euthyroid twin. In
1 case, central hypothyroidism was hypothesized, once the
screening neonatal TSH test was normal and the diagnosis
was made at age of 78 days. Extrathyroid malformations were
present in 75% of cases. Conclusion: Our cases show that
discordance of twins for CH is the rule. Epigenetic modifications, early somatic mutations or stochastic developmental
events could be an explanation.
Keywords: twins; congenital hypothyroidism; thyroid malformation.
PO190 FOLLOW-UP OF CHILDREN WITH TSH BETWEEN
5 AND 10 MIU/L ON THE NEWBORN SCREENING TEST:
PRELIMINARY RESULTS
Christensen FC1; Sewaybricker LE1; Mendes-dos-Santos CT1; Goto MMF1;
Gabetta CS1; D’Souza-Li L1; Guerra-Junior G1; Lemos-Marini SHV1
1
State University of Campinas (UNICAMP) Introduction: UNICAMP neonatal screening program for
congenital hypothyroidism (CH) recalls newborns with dry
blood spot TSH levels (b-TSH)≥5 mIU/L for thyroid function evaluation. Objective: To verify the thyroid function
evolution in children with b-TSH≥5 and <10 mIU/L diagnosed with hypothyroidism in the first 2 years of life. Methods:
Children born between 2003 and 2010 were evaluated retrospectively. Selection criteria included children with b-TSH≥5
and <10 mIU/L, treated in the first 2 years of life due to serum
TSH (s-TSH) ≥10 mIU/L, either on the confirmatory test or
on a follow-up exam, with normal or low free T4 (FT4). In
the late thyroid function assessment (s-TSH and FT4), after
the age of 2 years, permanent hypothyroidism was considered when L-thyroxin replacement was reintroduced due to
s-TSH ≥10 mIU/L after at least 1 month of drug withdrawal.
Results: From 380,741 screened newborns, 3,713 presented
b-TSH ≥5 and <10 mIU/L and 339 (9.1%) had s-TSH ≥10
mIU/L and were treated. Thirty-five children were excluded
for prematurity, neonatal anoxia or maternal hyperthyroidism, 13 for Down syndrome and 42 for loss of follow-up or
no late thyroid profile check. From 249 children (146 males),
78 had permanent hypothyroidism on the late thyroid function revaluation, 4 with thyroid dysgenesis (2 lobe agenesis,
1 thyroid hypoplasia and 1 lobe reduction). Conclusion: The
use of b-TSH≥5 mIU/L cutoff point allowed the diagnosis of
249 children with CH that would not be detected with the
current recommended cutoff value (10 mIU/L). From them
31.3% confirmed hypothyroidism after the age of 2 years, 4
had thyroid dysgenesis.
Keywords: neonatal screening/methods; congenital hypothyroidism/diagnosis; thyrotropin/blood.
PO191 EVOLUÇÃO CLÍNICA DO HIPOTIREOIDISMO
SUBCLÍNICO EM CRIANÇAS E ADOLESCENTES
Villagelin D1; Santos RB1; Cunha MP1; Romaldini JH1
1
Pontifícia Universidade Católica de Campinas (PUC/Campinas) Introdução: O hipotireoidismo subclínico em crianças e adolescentes é um assunto controverso, não existindo consenso
sobre o tratamento. Objetivos: Avaliar a função tireoidiana
em crianças e adolescentes com hipotireoidismo subclínico
após um período de tratamento com levotiroxina (L-T4).
Métodos: 24 pacientes (16 mulheres, 8 homens) entre 7 e
18 anos, com diagnóstico de hipotireoidismo subclínico em
tratamento com L-T4 por um período que variou de 6 a 12
meses. Essa reposição hormonal foi suspensa por 60 dias,
quando foram determinados os valores séricos de TSH, T4
livre, anticorpos antitireoidianos e ultrassonografia (US) da
tireoide. Resultados: Concentração inicial de TSH (pré-tratamento) foi de 8,0 + 2,5 mU/L (4,88-13,61 mU/L); 16% apresentavam anticorpo antitiroglobulina positivo, enquanto 29%
apresentavam anticorpo antiperoxidase positivo. Alterações
dos US da tireoide foram encontradas em 62,5% dos pacientes. Durante a reposição hormonal com L-T4, a concentração de TSH diminui significativamente (2,2+1,6 mU/L; 0,01
a 6,11 mU/L; p<0,0001) e, após a suspensão da L-T4 por 60
dias, o valor de TSH aumentou significativamente (12,5+19,7
mU/L; 3,19 a 100 mU/L; p<0,001). TSH foi maior que 7
mU/L em 54% dos pacientes, após 60 dias sem L-T4. O valor
de T4 livre também variou significativamente: inicial, 1,2+0,7
ng/dL; durante LT4, 1,4+0,1 ng/dL, p<0,002; e 60 dias após
suspensão, 1,1+0,3 mU/L, p<0,002. Conclusão: Nossos resultados indicam que o hipotireoidismo subclínico na faixa etária pediátrica deve ser conduzido como no adulto e deve ser
tratado com L-T4.
Palavras-chave: hipotireoidismo; crianças; tratamento.
Thyroid Regulation
PO192 THIMEROSAL INHIBITS IODOTHYRONINE
DEIODINASE ACTIVITY
Pantaleão TU1; Padron AS1; Ferreira ACF1; Carvalho DP1; Rosenthal
D1; Correa da Costa VM1
1
Instituto de Biofisica Carlos Chagas Filho/Universidade Federal do Rio de
Janeiro (IBCCF/UFRJ)
Background: Thimerosal (sodium ethylmercury-thiosalicylate) is an antibacterial compound used in vaccines.
Both type 1 (D1) and type 2 (D2) iodothyronine deiodinases catalyze T4 activation into T3. Deiodinase activity can be
affected by increased reactive oxygen species, which can be
generated by NADPH oxidases (NOX). Objectives: We aimed
to examine the effect of thimerosal on D1, D2 and NOX activities. Methods: In vitro D1 and D2 activities were determined in the presence of different thimerosal concentrations.
In vivo effect of thimerosal on D1, D2 and NOX activities
was evaluated in female Wistar rats treated with thimerosal
[0.25 mg/100 g BW and 250 mg/100g BW, i.m., twice a week,
1 month]. Results: In vitro D1 and D2 activities were inhibited by thimerosal, in a dose-dependent manner, in all tissues
analyzed (D1: kidney, liver and pituitary; D2: hypothalamus,
pituitary, hippocampus and brown adipose tissue). In vivo,
kidney and pituitary D1 and hypothalamic, pituitary, hippocampus and cerebral cortex D2 activities were reduced in animals treated with the higher thimerosal dose, while liver D1
91
Abstracts: Poster
and cerebellum D2 activities were not affected. Kidney, pituitary, hippocampus and cerebral cortex NOX activities were
reduced in animals treated with the higher thimerosal dose,
while liver and cerebellum NOX activities were not altered.
Conclusions: Our data show that thimerosal is able to inhibit
D1 and D2 activities both in vitro and in vivo, although the
inhibition was not observed in all tissues studied. This inhibition is not consequence of increased ROS production by
NOX, since NOX activities were reduced or unaltered.
Keywords: iodothyronine deiodinases; thimerosal; NADPH
oxidase.
PO193 EFEITO DA INGESTÃO CRÔNICA DE CINAMALDEÍDO
SOBRE A FUNÇÃO TIREOIDEANA DE RATOS SAUDÁVEIS
Gaique TG1; Bento-Bernardes T1; Medeiros RF1; Pereira-Toste F1;
Oliveira KJ1 1
Universidade Federal Fluminense (UFF) Introdução: Recentes estudos in vivo e in vitro que investigam o cinamaldeído (CIN), componente purificado da
canela, demonstram ação benéfica desse composto sobre a
homeostase glicêmica e lipídica, parâmetros conhecidamente
regulados por hormônios tireoidianos (HTs) e mediados por
receptores nucleares (TRs). Objetivo: Investigar uma possível associação entre cinamaldeído e função tireoidiana,
estudando em ratos saudáveis o efeito da suplementação
crônica desse composto sobre a concentração e a ação dos
HTs. Métodos: Ratos Wistar, machos, adultos, foram suplementados por gavagem, durante 30 dias, com CIN (20mg/
kg pc/dia) ou veículo (DMSO 0,05%), grupo controle (CT).
Ingestão alimentar e massa corporal foram avaliados semanalmente. Ao final do tratamento, a massa do tecido adiposo
branco visceral (TAB) foi medida, as concentrações séricas
de T3 e T4 totais foram quantificadas por radioimunoensaios
específicos (n=9-11), e a expressão do RNAm dos TRs (isoformas a e b) hepáticos foi analisada por PCR em tempo real
(n=7). Resultados: Não houve diferença na massa corporal
final e ingestão entre os grupos CIN e CT, enquanto a massa
do TAB foi menor (-21%, p=0,0161) no CIN comparado ao
CT. Encontramos maior concentração sérica de T4 (+14%,
p=0,044) e menor concentração de T3 (-28%, p=0,012) no
grupo CIN comparado ao CT. A expressão do RNAm do
TRb hepático foi menor em relação ao CT (-33%, p=0,028)
sem alteração da expressão do TRa. Conclusão: A ingestão
crônica de CIN modifica a função tireoidiana de ratos e reduz
a expressão da principal isoforma do TR hepático. As consequências dessa modulação estão sendo investigadas.
Palavras-chave: hormônios tireoidianos; cinamaldeído;
receptores nucleares para hormônios tireoidianos.
PO194 UP-REGULATION OF ADIPONECTIN MRNA
BY INDIRECTLY ACTION OF TRIIODOTYRONINE IN
ADIPOCYTES, 3T3-L1
Oliveira M1; Olimpio RMC1; Sibio MT1; Luvizotto RAM1; Costa LPL1;
Conde SJ1; Moretto FCF1; N C R1 1
(FMB/UNESP) Adipose tissue produces adiponectin and is an important target of thyroid hormones (TH). Several studies have attempted
to relate the synthesis of adiponectin with TH. The aim was
to examine the effects of TH, triiodothyronine (T3), in the
92
modulation of adiponectin mRNA expression and the involvement of signaling pathway phosphatidyl inositol 3 kinase
(PI3K) in adipocytes cell culture, 3T3-L1. We examined the
involvement of these pathways in mediating TH effects by
treating adipocytes, 3T3-L1 with 10-6 M T3, incubation for 1
hour, in the absence or presence of either the PI3K inhibitor
(LY294002-LY). To examine whether adiponectin is indirectly induced, we used the translation inhibitor cycloheximide
(CHX). For mRNA expression analyzes was used RT-qPCR.
All experiments were performed in biological triplicate.
Statistical analysis was performed using ANOVA, complemmented with Tukey‘s test. The P <0.05 was considered significant. T3 increased the adiponectin mRNA expression of 1
(±0.22) to 2.86 (±0.011, p<0.001). This increase was preservated by LY294002 (3.55,±0.48, p<0.05), but abrogated in the
presence de CHX (0.68,±0.08, p<0.05). However in the presence of LY without the addition of T3 showed an increase of
adiponectin from 1 (±0.22) to 7.2 (±0.0,24, p<0.001). These
results demonstrate that activation of PI3K cytosolic signaling pathway is necessary to indirect T3 action on the adiponectin gene expression of the adipocytes, 3T3-L1. However
PI3K pathway is necessary to modulate normal levels of adiponectin in these cells.
Keywords: adipocytes; adiponectin; triiodothyronine.
PO195 THYROID HORMONE TRANSPORT AND
METABOLISM IN MICE DENDRITIC CELLS: EXPRESSION OF
GENES INVOLVED.
Gigena N1; Alamino VA1; Montesinos MM1; Nazar M1; Masini-Repiso
AM1; Cremaschi GA2; Pellizas CG1
1
CONICET); 2Instituto de Investigaciones Biomédicas (BIOMED-CONICET),
Universidad Católica Argentina Background: We reported thyroid hormone (TH) action at
dendritic cell (DC) level (Mascanfroni et al. FASEB J 2008;
22: 1032 and J Biol Chem 2010; 285: 9569; Montesinos et al.
Steroids 2012; 77: 67). However, the mechanisms involved
in TH transport and metabolism in DC are yet unknown.
Objetives: Explore in DC the expression of: 1) TH transporters: Monocarboxylate Transporter 8 (MCT-8), MCT-10 and
Organic Anion Transporting Polypeptide 1C1 (OATP1C1),
2) Deiodinases of iodothyronines: Dio1, 2 and 3, and
T3-induced effects on that expression. Methods: Mice immature DC were maturated with T3 (10 nM) or LPS (100 ng/
mL) for 18 h. The presence and levels of the mRNAs coding
the proteins mentioned above were evaluated through conventional RT-PCR and Real-time RT-PCR. The identity of
each mRNA was confirmed by Nested RT-PCR and Genetic
Sequencing. Results: 1) DC express only mRNA-MCT-10,
not MCT-8 or OATP1C1, and the expression of mRNAMCT-10 is higher in matured DCs than in immature DCs.
2) DC express mRNA-Dio2 and Dio3 but not Dio1, and T3
increased mRNA-Dio3 levels. Conclusions: This work revealed mRNA-MCT-10 expression, suggesting that the coded
protein functions as a TH transporter in DC. Besides, the
expression of mRNA-Dio2 and Dio3 suggests that their proteins may act in the activation-inactivation of TH in DC. In
addition, T3 participates in the regulation of Dio3 expression.
Although additional studies at protein level are necessary to
further disclose these issues, our findings provide the first
evidences of TH transport and metabolism in DC.
Keywords: deiodinases; MCT-10; dendritic cells.
Abstracts: Oral
ORAL
Thyroid Regulation
OR01 TISSUE-SPECIFIC REGULATION OF TRANSPORTERS
MCT8 AND MCT10 MRNA BY THYROID HORMONES
Pereira GF1; Almeida HN1; Império GE1; Bargi-Souza P2; Faustino LC1;
Santiago LA1; Nunes MT2; Ortiga-Carvalho TM1
1
Universidade Federal do Rio de Janeiro (UFRJ); 2Universidade de São Paulo
(USP) Background: Thyroid hormones (THs) transport process is
mediated by transporters such as Mct8 and Mct10. Earlier
we demonstrated that hypothyroidism and hyperthyroidism
inhibit expression of Mct8 and Mct10 in liver of mice. While
in pituitary, Mct8 mRNA was reduced by T3. Objective: To
evaluate if membrane transporters Mct8 and Mct10 are
regulated by THs in liver, heart and in a thyrotrope cell
line. Methods: Hypothyroid (PTU 0.15%) or euthyroid mice
received single injection of T3 or T4 (50mg/100g of BW) 30, 60
and 180 minutes before the sacrifice. Left ventricule and liver
were collected. Thyrotrope cells (Tat1) were treated or not
with DRB (Dichloro-1-b-D-ribofuranosylbenzimidazole), a
transcription inhibitor, for 2h, and afterwards with T3 10-10M
for 30 minutes. Mct8 and Mct10 mRNA expression was evaluated by real-time RT-PCR and the poly(A)tail length of
the Mct8 mRNA through RACE-PAT. Results: T3 increased
Mct8 (230%, p<0.001) and Mct10 expression in liver. Sixty
minutes, after hypothyroid animals have been treated with
T4 there was an increased expression of Mct8 (169%, p<0.05)
and T3 Mct10 (294%, p<0.001), respectively. Our preliminarily RACE-PAT results indicated that T3 increases the poly(A)
tail length of Mct8 mRNA, which might be contributing
for the increased content of Mct8 mRNA observed. Acute
T3 administration did not change the transporters mRNA
expression in the ventricle. T3 decreased the expression of
Mct8 (47.9%, p<0.01) in thyrotropes cells and this effect was
prevented by DRB. Conclusion: Our data indicate that THs
regulate their own transporters mRNA expression in a tissue
specific manner, by genomic and nongenomic mechanisms.
Tables: resumo_guilherme_final Lats 2013.doc
Keywords: Mct8; thyroid hormones transport; nongenomic.
NTI Syndrome
OR02 NONTHYROIDAL ILLNESS SYNDROME ALTERS
EXPRESSION OF GENES INVOLVED IN TRANSPORT AND
ACTION OF THYROID HORMONES
Cabanelas A1; Fontes KN1; Ramos MBA1; Silva PL1; Pazos-Moura
CC1; Rocco PR1; Ortiga-Carvalho TM1
1
Janeiro (IBCCF/UFRJ) The intracellular concentration of triiodothyronine (T3) can
be different from the plasmatic one. This is a result from entry
of thyroid hormone (TH) through thyroid hormone transporters, conversion of thyroxine (T4) to T3 by deiodinases
(D1 and D2) and binding of T3 to its nuclear receptor (TR).
Many diseases are able to decrease serum T3 (Nonthyroidal
illness syndrome – NTIS). In rodents, NTIS causes low serum
T4 and T3. Moreover, differences on the mRNA expression
of deiodinases and TR have been described in NTIS. The
current study evaluated variations on mRNA expression by
real-time RT-PCR of MCT8, MCT10, D1, D2, D3 and TRb
in mice with NTIS, in 2 different conditions: sepsis induced
by cecal ligation and puncture surgery and fastingfor 48h
and 72h. Blood, liver and pituitary samples were taken. In
male mice, fasting reduced body weight (22%) and decreased serum T4 (C=2.67±0.26 mg/dL; F=below test limit) and
T3 (C=80.14±3.96; F= 49.84±4.60 ng/dL) after 48 h. Liver
D1 expression also decreased (C=1.00±0.19; F= 0.37±0.10).
In female mice, 72h-fasting reduced body weight (38%), and
decreased serum T4 (C=2.50±0.22 mg/dL; F=below test limit)
and T3 (C=85.51±2.89; F= 62.76±4.21 ng/dL). Fasting
also decreased liver MCT8 (C=1.00±0.13; F=0.41±0.09).
Twenty-four hours after sepsis induction, serum T4 was
reduced (C=3.07±0.04; CLP=1.83±0.27) with no change
in serum T3. MCT8 increased with sepsis in the liver
(C=1.00±0.15; CLP=7.96±2.79) and D1 increased in the
pituitary (C=1.00±0.12; CLP=2.81±0.46). Our results so
far have shown that NTIS is able to alter mRNA expression
of genes involved inTH action depending on the disease
or tissue studied. Tables: Resumo LATS 2013 Dri extendido
final.doc
Keywords: MCT8; fasting; sepsis.
OR03 CARDIAC HYPERTROPHY MEDIATED BY THYROID
HORMONE RECEPTOR-B: POSSIBLE ROLES OF MIRNA-208
Império GE1; Pereira GF1; Ramos IPGF1; Santiago LA1; Almeida NAS2;
Fuziwara CS3; Kimura ET3; Olivares EL2; Ortiga-Carvalho TM1 1
Universidade Federal do Rio de Janeiro (UFRJ); 2Universidade Federal Rural
do Rio de Janeiro (UFRRJ); 3Universidade de São Paulo (USP) Background: Triiodotironine (T3) is critical for cardiac
function. Heart expresses TRa1 e TRb1, the 2 main thyroid
hormone (TH) receptors (TR). It is unclear, however, the
role of TRb1 on T3-induced cardiac hypertrophy. Objective:
Investigate the role of TRb1 on T3-induced cardiac hypertrophy. Methods: Adult male mice, wild-type (WT) or
homozygous (HO) for D337T mutation on TRb (unable to
bind T3), were used. Animals were studied at baseline, after
hypothyroidism (PTU) and hyperthyroidism (PTU+T3)
induction. Echo- and electrocardiogram were performed.
Hearts were collected, weighed and total RNA was extracted. Expression of mRNA and miRNAs were quantified by
real time RT-PCR. Results: T3 caused cardiac hypertrophy in
WT, but not in HO animals when evaluated by cardiac index
(WT-PTU: 119.3±6.0, WT-PTU+T3: 64.14±2.21, p<0.001) or
by echocardiography (WT-PTU: 200.1±26.15, WT-PTU+T3:
132.6±32.78 mg, p<0.05). Absence of a functional TRb1 altered several parameters in HO function. Left ventricular end
diastolic volume increased by 50% (p<0.05) in WT-PTU+T3
versus WT-PTU, but did not change in HO. Evaluation of
cardiac function showed important deterioration in cardiac
function in the absence of T3 ligation to TRb. Stroke volume
and ejection fraction dropped in HO-PTU+T3 vs. HO-PTU.
P wave reduced (50%, p<0.001) and heart rate increased
(p<0.05) on WT-PTU+T3 versus WT-PTU; but not in HO.
Analysis of MicroRNAs miR-1 and miR-208, involved in cardiac hypertrophy, showed that T3 treatment increased both (2
to 3 times) in a different fashion, being miR-1 TRb independent and miR-208 TRb dependent. Conclusion: TH-induced
cardiac hypertrophy is TRb-dependent and involves miR208, while the absence of T3 ligation on TRb promotes a
significant deterioration in cardiac function. Tables: Lats
93
Abstracts: Oral
2013 - cardiac hypertrophy mediated by thyroid hormone
receptor-b possible roles of mirrna-208.doc
Keywords: thyroid hormone; cardiac hypertrophy; miRNA.
OR04 DENDRITIC CELLS (DC) MATURED WITH
TRIIODOTHYRONINE (T3) IN THE PRESENCE OF TUMOR
ANTIGENS INDUCE A POTENT ANTITUMORAL RESPONSE:
ROLE OF T3 AS ADJUVANT IN DC-BASED CANCER
VACCINES
Alamino VA1; Gigena N1; Montesinos MM1; Donadio AC1; Milotich SI2;
Masini-Repiso AM1; Rabinovich GA3; Pellizas CG1
1
Centro de Investigaciones de Bioquímica Clínica e Inmunología/ Facultad de
Ciencias Químicas/Universidad Nacional de Córdoba (CIBICI/CONICET);
2
Hospital Materno-Neonatal Ramón Carrillo, Sanatorio Allende; 3Instituto
de Biología y Medicina Experimental/ Universidad Nacional de Córdoba
(IBYME-CONICET) Background: We demonstrated that mice DC express thyroid
hormone receptor b1 and that T3 stimulates DC maturation,
IL-12 production and T cell allostimulatory capacity directing
a T1-type response (FASEB J. 2008; 22: 1032) involving Akt
and NFkB activation signals (JBC. 2010; 285: 9569). Moreover,
T3 increased DC ability to stimulate cytotoxic antigen-specific
responses and antigen cross-presentation (RAEM. 2010; 47:
77). Objectives: 1) To evaluate apoptosis in T3-treated DC; 2)
To analyze the migratory capacity of T3-stimulated DC, 3) to
assess the capacity of T3-matured DC in the presence of tumor
antigens to stimulate an antitumoral response in vivo. Methods:
Mice bone marrow derived DC were pulsed with T3 (5nM)
for 18 h. Apoptosis and DC migratory ability were analyzed
by standard methodologies. For mice antitumor vaccination,
B16-OVA melanoma model was used and immunizations with
T3-pulsed DC in the presence of OVA were administered at
1, 3, 5 and 8 days after tumor cell inoculation. Tumor size was
measured with vernier calipers and mice survival registered.
Lymphocyte T linage was determined in tumor infiltrating cells
and IFN-g measured in esplenocytes. P<0.05 was considered
significant (ANOVA-SNK, Gehan-Bislow-Wilcoxon). Results:
1) T3 reduced DC apoptosis, 2) T3 increased DC migration
to lymph nodes, 3) T3-stimulated DC-based immunotherapy
was able to reduce the incidence of tumor establishment and
tumor growth in affected mice, prolonging their survival. These
effects were mediated, at least in part, by CD8+ T cells able to
secrete IFN-g. Conclusions: Results strongly suggest significant adjuvant properties of T3 in DC-based tumor vaccination
with profound implications in cancer immunotherapy. Tables:
Alamino.pdf
Keywords: Triiodothyronine; Dendritic cells; Tumor immunotherapy.
OR05 THYROID HORMONES MAINTAIN THE
PROLIFERATIVE PHENOTYPE IN T CELL LYMPHOMAS
THROUGH NUCLEAR AND MEMBRANE-INITIATED
TRANSCRIPTIONAL PROGRAMS
Cayrol F1; Fernando T2; Díaz Flaqué MC1; Genaro AM3; Farías R4;
Cremaschi G1; Cerchietti L2
1
Instituto de Investigaciones Biomédicas/Consejo Nacional de Investigaciones
Científicas y Técnicas/Universidad Católica Argentina (CONICET/UCA);
2
Weill Cornell Medical College of Cornell University; 3Centro de Estudios
Farmacologicos y Botanicos/Consejo Nacional de Investigaciones Científicas
y Técnicas/Universidad de Buenos Aires (EFYBO/CONICET/UBA);4Instituto
Superior de Investigaciones Biológicas/Consejo Nacional de Investigaciones
Científicas y Técnicas(INSIBIO/CONICET) Background: T-cell non-Hodgkin lymphomas (T-NHL) are a
heterogeneous group of lymphoproliferative disorders with an
94
aggressive clinical course and no specific treatments. Thyroid
Hormones (THs) are important regulators of differentiation,
growth and metabolism in normal T cells. Recent studies from
our laboratory showed that THs stimulate the proliferation
of T-NHLs through complimentary intracellular pathways
involving both the canonical nuclear receptor (TR) and a
membrane receptor (mTR) that for most cells are represented
by RGD integrin dimers. Objectives: Characterize the THs
regulated pathways and determine their relative influence on
the T-NHL malignant phenotype. Methods: We analyzed the
effect of T3/T4 through TR and mTR in eight human cell lines
representing the spectrum of T-NHLs. In order to discriminate between nuclear (total) vs. membrane-initiated effects of
TH, T-NHL cells were treated with physiological concentrations of free T3/T4 and cell impermeable agarose-bound T3/
T4 (TH-AG) at different time points. Results: T-NHL expressed higher levels of TRs and putative mTRs genes compared
to normal T cells. We found that both TH-free and TH-AG
increased the proliferation of T-NHL and the proliferative
intracellular signaling cascasde. By RNA-sequencing in 1 of
the cell lines we found activation by free THs of TR (including
up-regulation of KLF9, BTEB, and NCOA7), TNFR and IL-2
pathways. While activation of the mTR receptor caused activation of genes involved in mitochondrial respiration, fatty-acid
synthesis, angiogenesis and DNA replication. Conclusions:
Our data suggest that TH is important inducers of cell proliferation in T-NHLs tby transcriptionally regulating major survival pathways in these cells.
Keywords: T-cell lymphoma; gene expression; thyroid hormone receptors.
OR06 MATERNAL TYPE 2 DEIODINASE THR92ALA
POLYMORPHISM IS ASSOCIATED WITH REDUCED
PLACENTAL ENZYME ACTIVITY BUT DOES NOT SEEM
TO BE ASSOCIATED WITH OFFSPRING THYROID
DYSFUNCTION
Dora JM1; Costa JD1; Ribeiro RVP1; Wajner S1; Leiria L1; Da Silva A1;
Crispim D1; Maia AL1
1
do Sul (HCPA/UFRGS) Background: The type 2 deiodinase (D2), a key enzyme for
intracellular activation of the prohormone T4 into the active
hormone T3, is expressed in the placenta and might interfere
in fetal-maternal thyroid hormone homeostasis. A previous
study from our group has shown that a single nucleotide
polymorphism in D2 (Thr92Ala) is associated with reduced
placental D2 activity. Notwithstanding, the consequences
of reduced placental activation of thyroid hormones during
fetal development remains to be clarified. Objective: Our
aim was to evaluate whether the reduced activation of T3 by
the placental tissue of patients harboring the D2 Thr92Ala
polymorphism is associated with thyroid hormone dysfunction in the offsprings. Methods: Consecutive singleton pregnant patients, 18-45-year-old, attending a tertiary care hospital were invited to participate. All participants underwent
genotyping of the D2 Thr92Ala polymorphism. Neonatal
thyroid stimulating hormone (TSH) levels were evaluated
by the newborn screening program that measures TSH in
a blood spot dried on filter-paper. Results: A total of 253
patients were included in this study. According to maternal
Abstracts: Oral
D2 genotype, clinical and laboratorial maternal and neonatal
baseline characteristics were not different among the genotype groups. Also, offspring TSH did not differ according
to the maternal D2 Thr92Ala genotype (0.71 [P75-25 1.310.41] vs 0.55 [P75-25 1.61-0.32] mU/L for Ala/Ala vs Thr/
Ala-Thr/Thr genotypes, respectively; p=0.79). Conclusions:
The D2 92Ala genotype, a genetic variant associated with
reduced placental thyroid hormone activation, does not
seem to be associated with offspring thyroid dysfunction.
Tables: Artigo_LATS_2013.doc
Keywords: type 2 deiodinase; thyroid hormones; Thr92Ala.
OR07 ELEVATED MATERNAL SUBCLINICAL
HYPOTHYROIDISM COULD BE RELATED TO BODY MASS
INDEX
Martínez AC1; Mosso L1; Rojas MP1; Margozzini P2; Solari S1; Lyng T1;
Ortiz JA1; Carvajal J1
1
Pontificia Universidad Católica de Chile; 2Universidad Católica de Chile
There are few studies on frequency of thyroid dysfunction in
Latin America and fewer in pregnant women. We postulate
that this frequency is significantly higher in Chile. We evaluated frequency and risk factors of functional and autoimmune thyroid disease in first trimester pregnant who initiated
antenatal care in primary outpatient health centers. We obtained demographic background, medical and obstetric clinical
records registered through practice. Women with history of
hypo or hyperthyroidism, thyroid surgery or administration
of radioiodine were excluded. Seven hundred twenty participants with average age 25.4±6.6 years and gestational age
8.8±2.4 weeks were found. Using the international 1st trimester TSH range (0.03-2.50 uUI/mL), the frequency of hypothyroidism was 0.97%, subclinical hypothyroidism 35.56 %
and subclinical hyperthyroidism 0.83%. Thyroid dysfunction
was equal in women with or without risk factors for thyroid
disease. We explored local reference ranges defining a normal
reference population, which included normal weight pregnant
without anti-TPO antibodies, and excluded those with low or
high T4 or TSH above normal range for our laboratory. Two
hundred seventy-four women met these criteria, 97.5 percentile for TSH concentration was 3.83 uUI/mL. Using this cut
off, the rate of subclinical hypothyroidism on first trimester
was 12%. We found a high frequency of obesity in our population and TSH was significantly higher in this group. Is possible that Chilean population presents a higher prevalence of
thyroid disease or the local reference range of thyroid function tests is different than that of the international standard.
We suggest considering BMI influence on TSH level.
Keywords: pregnancy; thyroid dysfunction; normal TSH
range.
Hypothyroidism
OR08 CARDIOVASCULAR RISK IN HYPOTHYROIDISM
Hissa MRN1; Hissa PNG1; Magalhães RA1; Hissa MN1 1
Hospital Universitário Walter Cantídio/Universidade Federal do Ceará
(HUWC/UFC) Thyroid hormones affect lipoproteins metabolism and have
effects on cardiac function and vascular disease. Thyroid
dysfunction results in dyslipidemic syndromes that increase
cardiovascular risk. Given the epidemic of coronary heart
disease, prediction risk tools have been created. LAP score
(lipid accumulation product) it’s a tool that is based on the
measurement of waist circumference and triglyceride concentration. Analyzed 44 patients followed by hypothyroidism or thyroid nodules between November 2011 and April
2012. Patients were grouped into treated hypothyroidism,
untreated hypothyroidism and control. LAP index was calculated: (waist circumference [cm] -58) x (triglycerides
[mmol/L]). Analyzing the levels of LAP score the median in
the control group was 63.7 (P25=30.5, P75=79.9), whereas
the treated group the median was 59.9 (P25=25.7, P75=94.2)
and the untreated group 82.0 (P25=39.8, P75=98.6), although
no statistically significant difference were observed. There
were also no significant difference between control, treated and untreated groups in total cholesterol (mean 214.17,
196.6, and 206.1 respectively), triglycerides (mean 142.1,
132.6, and 147.6). The mean levels of HDL (51.2, 58.4, 46),
cholesterol were lower in the untreated group with statistical
significance close to 5%, suggesting a trend in difference. It
was observed a trend of better lipid profile; lower total cholesterol, lower triglycerides, higher HDL in treated group. The
LAP showed a median score higher among patients untreated. Further research it’s will help to establish the role of LAP
in analysis of cardiovascular risk for hypothyroidism patients.
Tables: Hipotireoidismo e risco cardiovascular.doc
Keywords: hypothyreoidism; LAP; waist circunference.
NTI Syndrome
OR09 EFFECT OF N-ACETYLCYSTEINE ON SERUM
THYROID HORMONE LEVELS IN THE ACUTE
NONTHYROIDAL ILLNESS SYNDROME
Vidart J1; Wajner SM1; Schaan BD1; Maia AL1
do Sul (HCPA/UFRGS) 1
Introduction: Nonthyroidal illness syndrome (NTIS) refers
to changes in thyroid hormone levels affecting up to 75%
of critically ill patients. Cytokines and oxidative stress have
been implicated as causative factors, as they derange deiodinase reactions. Addition of N-acetylcysteine (NAC) in a
cell model prevented the effect of Interleukine-6 on deiodinases, probably through a mechanism that restores catalytic
activity of the enzyme protein. NTIS is a marker of poor
prognosis during myocardial infarction (MI). Here, we
investigate whether NAC administration would prevent the
decrease of serum thyroid hormone levels observed in MI.
Methods: This was a randomized, multicenter clinical trial.
Patients with MI within 12 hours of evolution were eligible.
Patients were randomized to receive NAC or placebo during
48 hours. Baseline characteristics, clinical history and blood
samples for baseline and serial measurements of thyroid hormones were collected. Primary outcome was the variation of
serum T3 levels. Results: Sixty-seven patients were included.
Baseline characteristics were similar between groups. Levels
of serum T3 decreased in the placebo group at 12h of follow
up (98.6 versus 86.8 mcg/dL, p=0.001) but did not in patients
randomized to NAC treatment (100.4 versus 96.9 mcg/dL,
p=0.396). Similar levels of T3 were observed in both groups
at 48 hs and on the 5th day. TSH levels were virtually identical between the groups. Discussion: In patients with MI,
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Abstracts: Oral
NAC attenuated the decrease in serum T3 levels. This might
be related to an attenuation of the oxidative stress effect in
the peripheral metabolism of thyroid hormone. Tables: Effect
of n-acetylcysteine on serum thyroid hormone levels in the
acute nonthyroidal illness syndrome.pdf
Keywords: nonthyroidal illness syndrome; oxidative stress;
deiodinases.
OR10 EVALUATION OF BONE AND MINERAL METABOLISM
IN PATIENTS WITH THE SYNDROME OF RESISTANCE TO
THYROID HORMONE
Cardoso LF1; De Paula FJA1; Maciel LMZ1
1
Division of Endocrinology/Department of Internal Medicine/School of
Medicine of Ribeirão Preto/University of São Paulo (USP) Background: Resistance to Thyroid Hormone (RTH) is a rare
disease characterized by elevated thyroid hormone and not suppressed TSH concentrations. In 85% of cases it is related to TRb
gene mutations. Objectives: To compare biochemical and densitometric features of 14 patients with RTH (RTHG) compared
to control subjects (CG). Methods: Serum measurements of
total calcium (TCa), albumin, inorganic phosphorus (iP), creatinine, alkaline phosphatase, osteocalcin, PTH, 25-hydroxyvitaminD, fibroblast growth factor-23 (FGF-23) and cross-linked
C-telopeptide and urinary measurement of calcium, phosphorus
and creatinine were performed. Renal threshold phosphate concentration (RTPC) was estimated. Bone densitometry with focus
on whole body (WB), lumbar spine (LS), total hip (HT), femoral neck (FN) and forearm was obtained. Nonparametric tests
were applied. Results: Results showed higher concentrations of
TCa (p=0.04) and corrected serum calcium for concentrations
of albumin (p=0.01), lower concentrations of iP (p=0.04) and
lower RTPC (p=0.03) in RTHG compared to CG. The FGF-23
concentrations were higher in children with RTH (p=0.04). The
bone mass was lower among adults in RTHG, in WB (p=0.02),
LS (p=0.05), and FN (p=0.05). The Z-scores were lower in the
RTHG in HT (p=0.04) and FN (p=0.05). Conclusions: These
data indicates alterations on bone mineral metabolism in
RTHG. The higher concentrations of calcium and lower bone
mass in RTHG than in CG associated with the results of studies using animal models with mutant mice, suggest that
RTHG may exhibit thyrotoxic bone phenotype. However,
it was not possible to point out a single pathophysiological
mechanism that justifies simultaneously all changes observed. Tables: 2013 LATS Paper.doc
Keywords: resistance to thyroid hormone; bone mineral
metabolism; bone densitometry.
Thyroid Regulation
OR11 PAX8 AND P65 ARE INVOLVED IN THE REDUCED
TRANSCRIPTION RATE OF SODIUM-IODIDE SYMPORTER
(NIS) INDUCED BY IODIDE EXCESS
Serrano-Nascimento C1; Nicola JP2; Masini-Repiso AM2; Nunes MT1
1
Department of Physiology and Biophysics/Institute of Biomedical Sciences
University of São Paulo (USP); 2Centro de Investigaciones en Bioquímica
Clínica e Inmunología/Consejo Nacional de Investigaciones Científicas y
Técnicas/Universidad Nacional de Córdoba (CIBICI/CONICET/UNC)
Background: Iodide excess triggers rapid events that regulate NIS expression in thyrocytes. Iodide treatment acutely
(30 min) reduces NIS mRNA poly(A) tail length and half-life.
96
However, 12-24 h after iodide exposure NIS expression reduction persists, even though there is no alteration in transcript
poly(A) tail length. Since Pax8 and p65 transcriptional factors
may act together to induce NIS gene expression, this study
aimed to investigate if they could be involved in the negative regulation of NIS expression induced by iodide excess
treatment for longer periods of time. Methods: PCCl3 cells
were transfected with plasmids containing NIS full promoter
region, NIS upstream enhancer (NUE) and mutated NUE on
Pax8 or p65 binding sites. Cells were treated for 12-24 h with
NaI (10-3M). Promoter activity was evaluated by luciferase
assay. Immunocytochemistry, nuclear/cytoplasmic proteins
fractionation and ChIP assay for both transcriptional factors
were also performed. Pax8 and p65 expression were evaluated
by Real-Time PCR/Western Blotting. Results: NIS promoter
activity was reduced 12-24 h after iodide treatment. This effect
was abrogated in cells transfected with NIS-mutated promoters. Iodide reduced nuclear and increased cytoplasmic Pax8
and p65 content, reduced the association of these factors to
NIS promoter, and did not alter their expression. Conclusions:
Iodide treatment for 12-24 h reduced NIS transcription rate by
decreasing PAX8 and p65 cytoplasm-to-nucleus translocation,
and consequently, their interaction to NIS promoter. This shows
that iodide autoregulatory effect on thyroid involves posttranscriptional and transcriptional mechanisms, which are
triggered in a distinct temporal pattern and guarantees iodide
uptake for proper thyroid hormone synthesis. Tables: Abstract
1 - Merck Prize.docx
Keywords: iodide excess; sodium-iodide symporter; Pax8
and p65.
OR12 TRANSCRIPTION FACTOR NKX2.5 UPREGULATES
H2O2 GENERATION AND INHIBITS IODIDE UPTAKE IN
PCCL3 CELLS
Penha RCC1; Santos MCS1; Cardoso LC2; Carvalho DP1; Ferreira ACF1
Universidade Federal do Rio de Janeiro (UFRJ); 2Universidade Federal
Fluminense (UFF) 1
Background: DuOx1 is the main source of H2O2 in rat
thyroid cell line (PCCL3), an essential cofactor for thyroid
hormones biosynthesis. Nkx2.5 is expressed during thyroid
embryogenesis (E8.5-12) and mutations in Nkx2.5 gene are
related to thyroid dysgenesis. Despite that, little is known
about the role of this factor on thyroid function regulation.
Objectives: Herein, we have investigated the effect of Nkx2.5
transfection on iodide uptake, H2O2 generation and thyroid
differentiation markers expression in PCCL3. Methods: 1.5
x105 PCCL3 cells were transfected with plasmid encoding
mouse Nkx2.5 or exposed to 1mM H2O2. Thyroid H2O2
extracellular generation was evaluated by Amplex red method,
radioiodide uptake was evaluated 45 min after Na125I addition to medium and mRNA levels by qPCR. Results: Nkx2.5
overexpression negatively regulated most thyroid differentiation markers, especially NIS, and reduced iodide uptake in
PCCL3, while increased DuOx1 expression and extracellular H2O2 generation. In order to establish a possible role of
H2O2 as a mediator of Nkx2.5 action, we treated cells with
1mM H2O2, in which both Nkx2.5 and DuOx expression
were upregulated, together with reduced iodide uptake and
NIS expression. Conclusions: Our data suggest that Nkx2.5
is able to stimulate H2O2 generation in PCCL3 cells and
the treatment with 1mM H2O2 induced Nkx2.5 expression.
Abstracts: Oral
Thus, radioiodide uptake reduction found in Nkx2.5 transfected cells and H2O2-treated cells might be related to oxidative
damage to NIS and/or to a direct effect of NKX2.5 regulating
NIS expression. In conclusion, Nkx2.5 seems to play a role
regulating thyroid cell differentiation under oxidative stress
condition. Tables: RESUMO PARA PRÊMIO.pdf
Keywords: Nkx2.5; H2O2; NIS.
OR13 LYSOSOMAL DEGRADATION AND CLATHRINMEDIATED ENDOCYTOSIS ARE INVOLVED IN IODIDEINDUCED REDUCTION OF NIS EXPRESSION AND ACTIVITY
Serrano-Nascimento C1; Nicola JP2; Calil-Silveira J1; Masini-Repiso
AM2; Nunes MT1
1
Department of Physiology and Biophysics, Institute of Biomedical Sciences,
University of São Paulo (USP); 2Centro de Investigaciones en Bioquímica
Clínica e Inmunología/Consejo Nacional de Investigaciones Científicas y
Técnicas/Universidad Nacional de Córdoba (CIBICI/CONICET/UNC) Background: Iodide excess reduces NIS expression through
transcriptional and posttranscriptional events. Although
some of them are known, there are a number of issues that
still need to be explored. This study aimed to investigate
whether NIS proteolysis and/or endocytosis are involved in
NIS expression/activity reduction induced by iodide excess
treatment. Methods: NIS total expression was evaluated in
PCCl3 cells/Wistar rats treated with NaI for 30 min to 48 h.
NIS plasma membrane content was evaluated by surface
biotinylation, immunofluorescence and flow cytometry. NIS
half-life was assessed in iodide-treated cells previously subjected to cycloheximide (10mg/mL). NIS activity was evaluated
through iodide uptake assay. The parameters described above
were investigated in cells previously treated with inhibitors
of lysosomal (bafilomycin/100nM) or proteasomal (Z-leuleu-leu-al/5mM) degradation pathways, and with inhibitors
of endocytosis mediated by lipid-rafts (nystatin/5mM) or clathrin (chlorpromazine/20mM). Results: Iodide excess decreased total NIS expression in all time points analyzed both in
vivo and in vitro, and reduced NIS plasma membrane content/
activity in a time-dependent fashion in vitro. NIS half-life was
diminished after iodide treatment. Bafilomycin and chlorpromazine treatments prevented the iodide-induced effects
described above. Conclusions: Iodide excess rapidly reduces
total NIS content and NIS half-life through the induction of
lysosomal degradation pathway. Moreover, iodide promoted
NIS internalization, which decreased NIS plasma membrane
content and activity. These data shows that, besides the posttranscriptional events that reduce NIS mRNA expression
and translation efficiency, iodide-induced reduction of NIS
expression/activity is also related to events that increase its
turnover, through the lysosomal pathway, and its internalization, through clathrin-mediated endocytosis. Tables: Abstract
2 - Merck Prize.docx
Keywords: NIS; iodide; proteolysis/endocytosis.
OR14 HYPOTHALAMUS-PITUITARY-THYROID AXIS IN
PERINATALLY EXPOSED RATS CAN BE DISRUPTED BY
A LARGELY-USED BROAD-SPECTRUM HERBICIDE –
GLYPHOSATE
Kizys MML1; Sena-Souza J1; Romano RM1; Frossard MM1;
Ortiga-Carvalho TM2; Maciel RMB1; Giannocco G3; Dias-da-Silva MR1;
Romano MA4; Chiamolera MI5 1
Universidade Federal de São Paulo (UNIFESP); 2Universidade Federal do
Rio de Janeiro; 3Faculdade de Medicina do ABC (FM/ABC); 4Universidade
Estadual do Centro-Oeste (UNICENTRO); 5Escola Paulista da Medicina/
Universidade Federal de São Paulo Introduction: Thyroid hormone (TH) is essential for life
and its production is regulated by hypothalamus-pituitarythyroid-axis (HPT). Recently, endocrine-disrupting-chemicals, including the most widely used herbicide Glyphosate,
have been implicated with adverse effects in the endocrine
system, but only few studies have been done to analyze effects
in the HPT-axis and there was no published data of effects
of glyphosate in this axis. Objective: Investigate effects of a
glyphosate-based-herbicide in TH production and its regulation by HPT-axis. Methods: Evaluate the effect of gestational
maternal exposure on possible disrupting effects in HPT-axis
of male-offspring, glyphosate Roundup Transorb was administered to mothers from GD18 to PND5 (control, 5 and 50
mg/kg). At PND90, blood was collected for hormonal dosages
(TSH, T3 and T4), pituitary and liver tissues were submitted to
analysis of ß-TSH, Deiodinase type-1 (DIO1), type-2 (DIO2)
and type-3 (DIO3) mRNA by RT-qPCR. Results: After treatment, animals showed a trend of serum T3 decrease without
apparent alterations in T4 concentration, with fall of mRNA
levels of DIO1 in the liver. In the pituitary, DIO2 presented an
important increase in mRNA levels, with no changes in ß-TSH
and DIO3 mRNA content. Conclusion: Glyphosate-basedherbicide used in this study disrupted peripheral conversion
from T4 to T3, possibly through altering the transcription of
DIO1 in the liver, but this alteration may be compensated at
pituitary level by an increase of DIO2 expression. In addition,
we need to take into account other possible effects of lower T3
levels kept more persistently upon long-term of glyphosate
environmental exposition. Tables: Glyphosate LATS young
investigator prize 2013.docx
Keywords: hypothalamus-pituitary-thyroid axis; endocrine
disruptors; glyphosate.
OR15 HYPOTHYROIDISM DURING PREGNANCY
INCREASES THE SEVERITY OF EXPERIMENTAL
AUTOIMMUNE ENCEPHALOMYELITIS IN THEIR ADULT
OFFSPRING
Albornoz EA1; Gonzalez PA1; Riveros T2; Cortes C3; Opazo MC1;
Carreño LJ2; Bueno SM2; Kalergis AM2; Riedel CA1 1
Facultad de Ciencias Biológicas Universidad Andrés Bello.Millennium
Institute on Immunology and Immunotherapy; 2Facultad de Ciencias
Biológicas. Pontificia Universidad Católica de Chile, Millennium Institute
on Immunology and Immunotherapy; 3Facultad de Ciencias Biológicas
Universidad Andrés Bello Background: Maternal thyroid hormones, (MTH) during
gestation play an essential role for the appropriate development of the fetus central nervous system (CNS). Based on this
and previous reports that support that thyroid hormones are
important for the immune system, we think that the progeny
gestated in hypothyroidism could suffer a strong inflammation
at the CNS after inducing an autoimmune disease like experimental autoimmune encephalomyelitis (EAE), a experimental model for multiple sclerosis. Objectives: To determine
whether rodents that were gestated in hypothyroidism will
suffer a strong EAE compared to mice gestated in euthyroid
condition. Evaluate the viability of oligodendrocytes derived
from rodents gestated in hypothyroidism and the astrogliosis. Methods: Gestational hypothyroidismwas induced in
rodents by methimazol administration. EAE was induced
to adult mice that were gestated or not in hypothyroidism.
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Abstracts: Oral
The intensity of EAE was evaluated using a clinical score and
immune cell infiltration and demyelination at the CNS was
evaluated by immunohistochemistry. Oligodendrocyte survival was evaluated after TNFa addition and by MTT and
TUNEL assay. Astrogliosis was evaluated by GFAP and iNOS
content. Results: We showed that the offspring gestated in
hypothyroidism condition suffer higher EAE score, demyelination, immune cell infiltration, astrogliosis and oligodendrocyte cell death than rodents gestated in the euthyroid
condition. Conclusions: These results suggest for the first
time that hypothyroidism during gestation can impair the
outcome of an inflammatory CNS disease, such as EAE in the
offspring. These data strongly support the need for thyroid
hormone diagnosis for pregnant women and the treatment
of hypothyroidism during pregnancy. Tables: Albornoz
LATS12.docx
Keywords: gestational hypothyroidism; multiple sclerosis;
central nervous system.
OR16 UNEXPECTED HIGH LEVEL OF CALCITONIN IN
PATIENTS WITH APPARENTLY CURED MEDULLARY
THYROID CARCINOMA: A NOVEL PITFALL IN THE
IMMUNOASSAY – THE “MACROCALCITONIN”
Alves TG1; Kasamatsu TS1; Yang JH1; Lindsey SC1; Camacho CP1;
Furuzawa GK1; Kunii IS1; Chiamolera MI1; Maciel RMB1; Vieira JGH1;
Dias da Silva MR1; Martins JRM1 1
Universidade Federal de São Paulo (UNIFESP) Introduction: Calcitonin (CT) represents a sensitive marker
of medullary thyroid carcinoma (MTC). Clinical challenge
may rise when patient presents mild CT increase without
corresponding structural disease found by imaging scan. This
lack of biochemical-clinical correlation may suggest assay
interferences, which can delay a suitable approach for the
patients. Objective: To investigate the presence of new assay
interferences in the serum of MTC patients who are apparently without structural disease. Methods: CT was measured
by an in-house immunofluorometric assay from 25 patients
(17F:8M, aged 16-67 years) with MTC. After precipitation
with polyethylene glycol (PEG) samples were subjected to gelfiltration on high performance liquid chromatography-HPLC
(Biosep S-3000 column, 30x6.7mm, Phenomenex) and to affinity chromatography on Protein A Sepharose (GE Healthcare).
Results: Serum CT ranged from 21-19.800 pg/mL. Three
patients showed low recovery of CT (1%-7%) after PEG when
compared with recovery of the others (55%-135%). Elution
profile on HPLC showed that almost all of the immunometric
CT from these 3 patients behaved as a high-molecular-weight
aggregate (MW>300 kDa). Additionally, when these samples
were applied to the protein A sepharose, CT immunoreactivity was almost completely retained on the column and only
released after lowering pH to 2.8. Conclusion: Our results
show for the first time the presence of a novel pitfall in the CT
immunoassay – the “Macrocalcitonin”. Its etiology, frequency
and meaning remain to be defined. However, rather than a
simple artifact, its recognition has a noteworthy interest
since it can help clinicians on the MTC follow-up, avoiding
unnecessary investigation and overtreatment. Tables: LATSmacrocalcitonina-Thalita-texto longo-FINAL.pdf
Keywords: calcitonin; medullary thyroid carcinoma; diagnosis.
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Thyroid Nodule
OR17 ARE ECHOGRAPHIC FEATURES RELEVANT IN
THE DIAGNOSIS OF MALIGNANT THYROID NODULES IN
ELDERLY PATIENTS?
Vera MI1; Meroño T1; Parisi C1; Urrutia A1; Cejas C1; Schnitman M1;
Zuk C1; De Barrio G1; Silveira R1; Morosan Y1; Rosmarin M1;
Serrano MS1; Serrano L1; Luciani W 1; Faingold MC1; Brenta G1
1
Unidad Asistencial Dr. César Milstein Background: Given that thyroid cancer is more prevalent
and aggressive in elderly patients, early diagnosis is crucial. Objectives: Our aim was to assess the diagnostic value
of different echographic features (EF’s) in the detection of
thyroid malignancy in elderly patients. Methods: We studied
every patient >45 years referred to US-FNAB (2008-2012)
with EF and cyto-histology. Both suspicious-for-malignancy
and malignant were considered as only 1 cytological category (S/Mc). Patients with insufficient or missing cytology
were excluded in the analyses (n=39). Cyto-histological correlation was evaluated with kappa coefficient (n=44). EF’s
were considered as presence/absence of solid-echostructure,
hypoechogenicity, microcalcifications, irregular margins,
high anterio-posterior (AP)/axial quotient and absent halo.
Logistic regression models used S/Mc as the dependent
variable. The association between >1 EF and S/Mc was calculated. Results: Out of 547 patients (age 69±7years, females:
92.2%/males: 7.8%), 508 nodules were evaluated by cytology:
79% were benign, 8% indeterminate and 5% S/M. After
excluding indeterminate cases, cyto-histological correlation
showed a Kappa coefficient=0.68, p<0.001. Predominant EF
was solid-echostructure and hypoechogenicity. Proportion
of microcalcifications and irregular margins was significantly higher in nodules with S/Mc. AP diameter associated
with S/Mc (r=0.14, p<0.005). By logistic regression, only
AP/axial quotient >1 and irregular margins were associated
with S/Mc. The combination of 5 EF or more in 1 nodule
showed the highest odds of S/Mc. Conclusion: In elderly
patients, certain EF regarding the shape of a thyroid nodule
such as “taller tan wider” and “irregular margins” should
alert on possible malignancy and lead to FNAB. The risk of
malignancy is further increased when 5 or more suspicious
EF’s are present together in a nodule. Tables: summary
LATS- 13-11-12.doc
Keywords: nodule; ultrasonography; elderly.
OR18 THYROTOXICOSIS DUE TO INCREASED
CONVERSION OF THYROXINE TO TRIIIODOTHYRONINE
IN A PATIENT WITH LARGE METASTASES OF FOLLICULAR
THYROID CARCINOMA TREATED WITH SORAFENIB
Liberati APT1; Dias EO1; De Castro G Jr2; Danilovick DS1; Hoff A2;
Camargo RYA1
1
Thyroid Unit of Hospital das Clinicas da Faculdade de Medicina da
Universidade de São Paulo;2Instituto do Câncer do Estado de São Paulo
(ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP)
Case report: In January 2006, a 63 year-old women came to
the Thyroid Unit with a history of total thyroidectomy for a
follicular thyroid carcinoma in 1998 and a recurrent tumor
in tibia that was surgically removed in 2003. She had already received radioiodine therapy with a dose of 150 mCi in
2009, 300 mCi in 2002, and 500 mCi in 2003. The laboratory tests showed a stimulated thyroglobuline (Tg) of 50 ng/
Abstracts: Oral
mL, T3=40 ng/dL, FT4=0.3 ng/dL, TSH=132.16 uU/mL, and
negative anti-Tg antibody. In 2007, multiple bone metastases were diagnosed in skull, vertebrae, ribs and left humerus
and she was submitted to an external radiotherapy treatment.
In October 2009, we observed an elevated T3 (297 ng/dL)
with a decreased FT4 (0.4 ng/dL), Tg>30.000 ng/mL, and
TSH<0.003 uU/mL so the dose of thyroxine was reduced.
She began treatment with Sorafenib, an inhibitor of tyrosine
kinase with a daily dose of 400 mg. There was a important
reduction in cranial tumor and the Tg level reduced to 3.100
ng/mL in July 2010 and the disease was considered stable
until August 2011. Sorafenib was discontinued in May 2012
because of disease progression. In July 2012 the Tg level was
10.277 ng/mL, TSH was 0.03 uU/mL, FT4 decreased to 0.65
ng/dL, and T3 elevated to 247 mg/dL. Conclusions: We described a rare case of T3 toxicosis probably due to increased
conversion of thyroxine to triiodotironina in a patient with
extensive metastases that was reversed with treatment with
Sorafenib. Tables: Resumo case report LATS 2013.doc
Keywords: thyroid cancer; folicular carcinoma; T3 toxicose.
OR19 CTLA-4 GENETIC PROFILE OF RISK FOR GRAVES
DISEASE IN THE IN BRAZILIAN POPULATION
Bufalo NE1; Rocha AG1; Secolin R1; PiaiRP1; Santos RB2;
Romaldini JH2; Ward LS1
1
Universidade Estadual de Campinas (UNICAMP); 2Pontifícia Universidade
Católica (PUC) The cytotoxic T lymphocyte-associated protein 4 (CTLA-4)
is a major determinant to the susceptibility to Grave’s disease (GD), playing a fundamental role in the heterogenic and
complex interaction of genetic, epigenetic and environment
factors involved in the disease. CTLA-4 acts suppressing T cell
activation and the subsequent immune response, in order to
prevent T-cell over-activity. Several CTLA-4 polymorphisms
have been found to be associated with autoimmunity. In
order to determine the role of CTLA-4 gene polymorphisms
in the susceptibility to GD, we studied 282 GD patients and
308 healthy individuals paired for age, gender and ethnicity.
CTLA-4 gene polymorphisms (rs231775, rs3087243 and
rs5742909) were genotyped by Real Time PCR TaqMan SNP
Genotyping®. A multivariate analysis demonstrated that the
inheritance of a CTLA-4CT60GG genotype increased the
risk for GD (OR=2.36; 95%; IC=1.65-3.39; p<0.0001). The
inheritance of polymorphic genotype of CTLA-4–318 gene
was associated with elevated serum TRAb levels (p=0.0229)
and with high therapeutic doses of radioiodine (p=0.0237)
compared to wild-type genotype. Patients who inherited the
polymorphic genotype were older (42.90±10.83 years-old)
than wild-type patients (38.84±11.81 years-old, p=0.0105).
Also, GD patients who inherited a heterozygote CTLA-4
CT60 genotype became pregnant less frequently (2.21±2.50)
than wild-type CTLA-4CT60 patients (3.03±2.58, p=0.0190).
There was no correlation between the investigated SNPs with
other patients’ clinical features. In conclusion, we demonstrate that CTLA-4 polymorphisms are associated to the susceptibility to GD in the Brazilian population and may identify
clinical features that may influence the clinical management
of these patients. Tables: 3 páginas.pdf
Keywords: graves disease; CTLA-4; polymorphisms.
Hyperthyroidism
OR20 THYROID VOLUME, POSITIVE TRAB, AND
THYROTOXICOSIS SYMPTOMS ARE RISK FACTORS
ASSOCIATED WITH THE NATURAL COURSE OF
ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM
Godi AC1; Nogueira CR2; Vilar HC1; Sgarbi JA1 1
Division of Endocrinology and Metabolism, Marília State School of Medicine;
2
Department of Internal Medicine, Botucatu School of Medicine, University of
São Paulo State
Background: There are limited data on the risks factors associated with the natural course of subclinical hyperthyroidism
(SCH). Objectives: To assess the spontaneous course of SCH
and the risks for the progression to overt hyperthyroidism
(OH) or to persist in SCH. Methods: Prospective cohort of
98 patients (mean age, 62.3 years) with endogenous persistent
SCH. Patients taking thyroid-altering medications or previously treated for hyperthyroidism were excluded. Results:
In a 57-months follow-up, 14.3% of patients progressed to
OH, 64.3% persisted in SCH, and 21.4% reverted to euthyroidism. Most patients with multinodular goiter (72%) and toxic
adenoma (69%) persisted in SCH (p=0.002), whereas patients
with GD progressed to OH (57%) or reverted to euthyroidism
(43%). Thyroid volume was higher among patients who persisted in SCH (p=0.01), and TSH levels were lower (p<0.01)
in patients who progressed to OH. Survival curves showed
that the progression to OH was related with thyrotoxicosis
symptoms (p=0.01) and positive TRAb (p<0.0001), whereas
TSH<0.1 mU/L with persistent SCH (p=0.01). In a multivariate regression analysis, thyrotoxicosis symptoms [OR,
8.8 (95% CI, 1.6–46) was a predictor for progression to OH,
whereas thyroid volume >50 g [1.04 (1.004–1.07) and heterogeneous features in thyroid scintigraph [5.9 (1.5–22.7)
were for persistent SCH. Conclusions: Thyrotoxicosis symptoms and positive TRAB were risk factors for progression to
OH, whereas thyroid volume and heterogeneous features in
thyroid scintigraph were for persistent SCH. Tables: LATS
FLORIANOPOLIS ABSTRACT.docx
Keywords: subclinical hyperthyroidism; natural history; risk
factors.
OR21 THE TYPE 3 DEIODINASE DISPLAYS HIGH CATALYTIC
EFFICIENCY IN THYROID HORMONE INACTIVATION UNDER
PHYSIOLOGICAL OR PHYSIOPATHOLOGICAL CONDITIONS
Wajner SM1; Rohenkohl HC1; Maia AL1 1
do Sul (HCPA/UFRGS) The role of deoidinases on normal thyroid hormone metabolism and pathological processes in humans has evolved in the
last decades. Nevertheless, little is known about the catalytic
efficiency of D3-catalyzed T3 inactivation. D3 is located at
the plasma membrane, but it remains uncertain whether the
T3 inactivation reaction occurs in the extra- or intracellular
space. Objective: To access the catalytic efficienciency of D3
in the T3-inactivation process, under the physiological conditions of FT3 and endogenous cofactor that obtain in vivo,
as well as to determine where the D3-catalyzed T3 inactivation reaction occurs. Methods: D3 and D1 activities were
measured by descending paper chromatography in intact
cells or sonicates in both transfected and cells endogenous
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Abstracts: Oral
expressing D1 (Hep-G2) or D3 (MCF-7). Results: The D3
catalytic efficiency in euthyroidism was ~135x higher than
D1, even considering that D1 has a 1000-fold higher Km for
T3. In the hypothyroid scene it was ~300x higher and 1,500x
higher under the hyperthyroid condition. To determine if the
D3-catalyzed reaction occurs in the extra- or intracellular
space we used the extracellular probe sulfo-NHS-LC-biotin
and intracellular probe biocytin. The addition of sulfo-biotin
to culture medium blocked D3 activity at 6h (19.1±2.2 vs.
5.8±0.7fmol/mg.prot) whereas D1 was unaffected (21.2±1.12
vs. 17.55±1.07pmol/mg.prot). The opposite occurred when
the intracellular probe, biocytin, was used. These results indicate that D3 is located at the extracellular space. Conclusion:
Our results suggest that D3 is the main T3 inactivating
enzyme under pathophysiological conditions and that D3
inactivating-T3 reaction takes place at the extracellular space.
Tables: LATS 2013 SMW.pdf
Keywords: thyroid hormone; deiodinases; thyroid hormone
metabolism
NTI Syndrome
OR22 SELENIUM PARTIALLY REDUCES THE EFFECT OF
OXIDATIVE STRESS MEDIATED BY INTERLEUKIN-6 ON THE
TYPE 3 DEIODINASE
Rohenkohl HC1; Maia AL1; Wajner SM1 1
Thyroid Section/Endocrine Division/Hospital de Clínicas de Porto Alegre,
Universidade Federal do Rio Grande do Sul (HCPA/UFRGS) Introduction: Nonthyroidal illness syndrome refers to
thyroid dysfunction in patients with systemic disease and
no changes in endocrine axis. Oxidative stress, generated
by IL-6, inhibits the function of deiodinases type 1 (D1)
and type 2 (D2) while induces the expression of deiodinase type 3 (D3). Sepsis is associated with increased IL-6,
oxidative stress and low plasma selenium levels, an endogenous antioxidant. Thus, supplementation with selenium
could reverse oxidative stress and deiodinase deregulation. Objective: To evaluate the effect of selenium on D2
and D3 activity under oxidative stress condition induced
by IL6. Methods: Cells expressing endogenous D2 or D3
(MSTO and MCF-7, respectively) were incubated in a model
that mimics the physiological conditions of substrate and
cofactor. Deiodinase activity was measured by I125 generated in the medium (D2) or descending paper chromatography (D3). Results: IL-6 significantly inhibits the T3 production by D2 even in the presence of selenium (100 nM)
(1063±26.66 versus 586.7±14.96 versus 454.6±7.035 versus
341.6±14.49 fmol/mg.prot/24h at 500 ng/L, 1000 ng/L and
2000 of IL-6, respectively; p <0.0001), whereas induces
D3 activity (5.7±0.08 versus 9.53±0.7 fmol/mg.prot/24h,
p<0.001). Interestingly, selenium (100 nM) was able to
attenuate the D3 induction (9.53±0.7 versus 6.9±0.34 fmol/
mg.prot/24h, p<0.05). Conclusion: Selenium seems to have
a distinct effect on deiodinases probably due to the augmented D2 susceptibility to decreased intracellular levels of
cysteine and the putative D3 location in the plasma membrane that could give ready access to the antioxidant effect
of selenium. Tables: Selenium partially reduces the effect of
oxidative stress mediated by interleukin-6 on the type 3 deiodinase.pdf
Keywords: selenium; deiodinase; oxidative stress.
100
OR23 IODINE BLOCKS SMAD4 INHIBITION BY MIR-19
AND RESTORES TGFB RESPONSIVENESS DURING BRAF
ONCOGENE ACTIVATION IN THYROID CELLS
Fuziwara CS1; Kimura ET1
1
Institute of Biomedical Sciences/University of São Paulo
Background: BRAFT1799A mutation is the most prevalent
alteration in thyroid cancer, associated with poor prognosis. However, iodine impact in BRAF-mediated oncogenesis remains unclear. Iodine exerts anti-proliferative effects
in thyroid cells associated to TGFB-pathway enhancement
and we showed that iodine excess protects thyroid cells from
BRAF-induced genomic instability. MicroRNAs are small
non-coding RNAs that target several mRNAs controlling protein expression. MiR-19 belongs to cluster miR-17-92 which
attenuates several tumor-suppressor genes and is predicted
to target TGFB-pathway components. Therefore, we aim at
analyzing the influence of iodine on microRNA-mediated
TGFB signaling control during BRAFT1799A activation.
Methods: BRAF9-6 cells, which express BRAFT1799A under
doxacyclin (Dox-group), were treated with iodine-containing
medium at 10-5M (Dox+NaI-group). Control was performed
without Dox/NaI. MiR-19 expression was performed by realtime qPCR and Smad4 target validation was performed by
Western-blotting and luciferase-assay. TGFB responsiveness
was analyzed through cell cycle of TGFB-treated cells by
flow-cytometry. Results: BRAFT1799A induction in thyroid
cells increased miR-19a/miR-19b in 634.3-fold/141.6-fold,
respectively (Dox x Control), while adding iodine prior to
induction resulted in 2.36-fold/0.66-fold levels (Dox+NaI
x Control). BRAFT1799A reduced Smad4 protein which
was restored by iodine treatment. Low Smad4 levels during
BRAFT1799A-activation resulted in impairment of responsiveness to TGFB in thyroid cells, while iodine-containing
medium restored inhibitory signal and rendered cells arrested in G1-phase. Bioinformatic search revealed Smad4 as
potential miR-19 target which was validated by luciferaseassay. Conclusion: Iodine abrogates BRAFT1799A-induced
loss of TGFB responsiveness through modulation of miR-19,
a new Smad4 regulator, indicating a role for microRNAs in
the escape of TGFB anti-proliferative effect. Tables: Resumo
expandido lats 2013.doc
Keywords: miR-19; BRAF mutation; thyroid cancer.
OR24 POTENTIAL ANTI-TUMORIGENIC EFFECTS OF AMPKINASE (AMPK) ON PAPILLARY THYROID TUMOR CELL
LINEAGES
Background: Although poorly understood, the role of AMPK
in carcinogenesis seems to be related to 2 opposing functions:
(1) promote the survival of tumor cells in unfavorable metabolic situations; (2) decrease cell proliferation. We recently
demonstrated that AMPK activation decreases iodine and stimulates glucose uptakes in PCCL3 cells, which also occurs in
thyroid tumor progression. Objective: To evaluate the effect
of AMPK activaton on papillary thyroid cancer cell lineages. Methods: Normal human thyrocyte lineage (NTHY-ORI)
and 2 papillary carcinoma lineages (BCPAP and TPC-1) were
treated with the pharmacological activator of AMPK, AICAR
Abstracts: Oral
(1 mM) for 24, 48 and 72 hours and then cell viability was
measured by MTT, cell proliferation was measured by crystal
violet, and to evaluate the adhesion, cells were pretreated with
AICAR for 24 h, trypsinized and plated in a 24 well plate at
the same density. AMPK protein expression was evaluated by
Western blotting and cell migration was assessed by “wound
healing assay”. Results: Total and phosphorylated AMPK are
expressed in the 3 different cell lineages, although with different intensities, however, the effects of AMPK activation were
similar in all the 3 lineages used. AICAR induced a significant
reduction of cell viability and proliferation. Interestingly, treatment with AICAR for 24 h provided an increase in cell adhesion in all lineages evaluated. Conclusion: AMPK activation
causes anti-proliferative effects in all the cell lineages tested. We
also demonstrated an increase in cell adhesion, which may be
related to lower cellular invasion ability, and consequently an
anti-tumorigenic action of AMPK. Tables: LATS 2013 - linhagens tumorais ingles premio.pdf
Keywords: AMPK; papillary thyroid carcinoma; AICAR.
OR25 ADIPONECTIN, LEPTIN, RESISTIN AND GHRELIN:
IN SEARCH OF THE LINKS BETWEEN OBESITY AND
DIFFERENTIATED THYROID CANCER
Batista FA1; Marcello MA1; Almeida JFM1; Cavalari C1; Rocha AG1;
Cunha LL1; Assumpção LVM1; Carvalho AL2; Ward LS1
1
Laboratory of Cancer Molecular Genetics/University of Campinas
(GEMOCA/UNICAMP); 2Head and Neck Surgery/Barretos Cancer Hospital We previously suggested that an alteration in adipokines
and ghrelin serum concentrations could link obesity to
Differentiated Thyroid Cancer (DTC) risk. In order to investigate if polymorphisms in ADIPOQ, LEP, LEPR, RETN,
GHRL, GHSR and their receptors (R) could influence their
serum levels and correlate with DTC risk, we investigated 21
polymorphisms in 153 DTC patients and 234 controls matched
for age, gender and Body Mass Index using TaqMan SNP
Genotyping® assays. Individuals with the genotype GG of the
rs3774262 presented higher serum levels (3.21+1.25 mg/mL) of
adiponectin than individuals with GA (2.74+1.43 mg/mL) and
AA (2.15+0.00 mg/mL; p=0.03557). Individuals with an AG of
the rs3774262 presented higher serum levels (10.02+1.35 ng/
mL) of leptin than individuals with AA (9.74+1.01 ng/mL)
and GG (9.29+1.30 ng/mL; p=0.00746). The inheritance of a
rs1501299GG variant of the ADIPOQ gene was associated to
menarche at earlier age (p=0.0018). Patients with Leptin GG
genotype (rs 7799039) had larger tumors (2.7+1.0 cm) than AG
(2.2+0.7 cm) and AA patients (1.1+0.4 cm; p=0.03117). The
inheritance of the AA genotype for the LEPR gene (rs 1137101)
diminished the risk of DTC when compared to altered (AG
or GG) individuals (OR=0.3915; 95% CI: 0.2084–0.7354;
p=0.0038). The RETN GG genotype (rs1862513) and the CC
genotype (rs3745369) were more frequent among overweight
(BMI>25.0 kg/m2) individuals. The inheritance of wild-type
GHSR genes (rs2232165 and rs572169), protected individuals of developing DTC (OR=0.2172; 95% CI: 0.0596–0.7906;
p=0.0151 and OR=0.4973; 95% CI: 0.2839–0.8714; p=0.0191,
respectively). Our results suggest that polymorphisms in adipokines and adipokines receptor genes might be related to the
susceptibility to DTC. Tables: Adiponectin, leptin, resistin
and ghrelin in search of the links between obesity and differentiated thyroid cancer.docx
Keywords: thyroid cancer; obesity; adipokines.
OR26 GENOME-WIDE COPY NUMBER ANALYSIS IN A
FAMILY WITH P.G533C RET MUTATION AND MEDULLARY
THYROID CARCINOMA IDENTIFIED REGIONS ASSOCIATED
WITH HIGHER PREDISPOSITION TO LYMPH NODE
METASTASIS
Araujo AN1; Moraes LS1; França MIC1; Maciel RMB1; Cerutti JM1
Universidade Federal de São Paulo (UNIFESP) 1
Background: The medullary thyroid carcinoma (MTC)
occurs in a sporadic (SMTC) or hereditary (HMTC) form.
Our group identified a new RET mutation (p.G533C) in a
family with MEN 2A. Clinical heterogeneity was observed
among the p.G533C-carries, mainly associated with tumor
aggressiveness. Objective: To investigate whether copy number variant (CNV), present in the constitutional DNA, is associated with higher predisposition to lymph node metastasis in
this kindred. Methods: Fifteen p.G533C-carriers with MTC
were divided into 2 groups according to presence of lymph
node metastasis (n=8) and absence of lymph node metastasis (n=7). DNA from peripheral blood was extracted by phenol/chloroform method, and its integrity evaluated on agarose gel. The DNA samples were independently analyzed by
Genome-Wide Human SNP Array 6.0 platform and the result
was evaluated using Genotyping Console software. The cases
(metastatic MTC) were compared to control (non-metastatic
group and normal – Hapmap) as a way to eliminate nonpathogenic CNVs. Results: We identified 7 CNVs that were
associated with presence of lymph node metastases; some of
them encompass non-annotated and annotated genes. The
validation steps by qPCR not only confirmed these findings
but also identified a CNV associated with a more aggressive
phenotype, observed as presence of lymph node metastasis
in this family (Fisher‘s Exact Test; ≤0.05), elevated calcitonin
levels and larger tumor (Mann Whitney ≤0.05). Discussion:
The CNV found through genome-wide copy number analysis
may be associated with higher predisposition to lymph node
metastasis in this family. Tables: XV LATS ALINE PAPER FINAL.pdf
Keywords: MTC; CNV; RET.
OR27 - PROGNOSTIC VALUE OF GROWTH FACTOR
SIMILAR TO INSULIN 1 (IGF-1) AND IGF-1 RECEPTOR
(IGF-1R) IN DIFFERENTIATED THYROID CARCINOMA (DTC)
WITH ENPHASIS ON LOW-RISK PAPILLARY THYROID
CARCINOMA
Dias EO; Basso M; Kanamura C; Galrao AL; Marui S; Camargo RY1 1
Thyroi Unit/Clinical Hospital of the University of São Paulo Background: Evidence suggests an important role of the
IGF system and insulin growth factor in clinical behavior of
various types of tumors. It is believed that activation of the
IGF system is a key factor in the progresssion of tumors,
resistance to apoptosis and therapies. Objective: To study the
expression and prognostic value of IGF-1 and IGF1receptor
in DTC, with emphasis on low-risk papillary carcinoma,
including the microcarcinoma. Patients and Methods: We
selected 41 patients who underwent surgery for DTC and subdivided into the following groups: 36 patients with papillary
carcinoma containing a subgroup of 18 papillary microcarcinoma and 5 Follicular carcinoma. We studied the expression
of IGF1 and IGF1-R by immunohistochemistry in tumoral
and non-tumoral tissues, and correlated the intensity/quan-
101
Abstracts: Oral
tity of expression with TNM and risk stratification. Results:
Both IGF1 and IGF1-R were overexpressed in all Follicular
carcinomas, and in 91.7% of Papillary carcinomas with a
range in intensity and quantity of cells stained for all 3 groups
of cancer and absent or weak expression in non-tumoral tissues. However, we highlight a variation within the heterogeneous group of Papillary Carcinoma, which expressed a
high staining intensity for IGF1 in a large numbers of cells.
No significant correlation was observed between TNM stages and risk stratification according the intensity or quantity
of cells expressed for IGF1 and IGF1-R. Conclusions: Our
data suggests that IGF and its receptor are overexpressed in
differentiated thyroid carcinoma when compared to the control non-tumor tissue, with no significant correlation to TNM
stage and risk stratification. Tables: Abstrat premio LATS-1
Elaine Dias.doc
Keywords: thyroid cancer; IGF; prognosis.
OR28 MIR-106B IS DOWN-REGULATED IN FOLLICULAR
CARCINOMAS AND MAY MODULATE C1ORF24
EXPRESSION BY INHIBITING C1ORF24 MRNA AND PROTEIN
EXPRESSION
Nozima BHN1; Carvalheira GMG1; Cerutti JM1 1
Universidade Federal de São Paulo (UNIFESP) Background: Our group have previously showed that
C1orf24 (alias NIBAN) is highly expressed in thyroid carcinomas when compared to benign lesions. However,
the molecular mechanism underlying its overexpression
remains unclear. Recently, the action of microRNAs (miRs),
a mechanism of gene regulation, has been widely investigated. miR expression varies according to the tissue, developmental stage and cancer cell type. Objectives: Identification
of miRs potentially regulating C1orf24 expression in thyroid
cell line and its validation. Methods: Candidate miRs that
could potentially regulate C1orf24 expression were identified using miRBase Sequence database. Endogenous levels
of C1orf 24 and miRs were evaluated by quantitative PCR
(qPCR) in 64 thyroid nodules. In order to over-express the
select miR into thyroid cells that shows high expression of
C1orf24, 6 thyroid cells were tested for both C1orf24 and
miRs expression by qPCR and Western blot. Results: The
expression analysis demonstrated that miR-106b was downregulated in malignant lesions when compared to benign
lesions (p=0.0060). When miR-106b was transiently transfected into the follicular thyroid carcinoma cell line (WRO),
both C1orf24 mRNA and protein levels decreased when
compared to negative control (p<0.05). Our initial findings
suggested that C1orf24 might interact with C1of24. Further
analysis will best determine this interaction. Conclusion:
These findings suggest that miR106b may modulate C1orf24
gene expression. Luciferase assay and functional analysis
has been performed to demonstrate if miR-106b interacts
with C1orf24 mRNA. Additionally, it may help the elucidation of the molecular mechanism underlying its activation in diverse tumor subtypes where it is highly expressed.
Tables: Resumo 3pag LATS microRNA 2013_FINAL.docx
Keywords: C1orf24; miR-106b; follicular carcinoma.
102
Thyroid Nodule
OR29 PRESURGICAL DETECTION OF BRAF V600E
MUTATION IN FNAB SPECIMENS AND CORRELATION WITH
AGGRESSIVENESS OF PAPILLARY THYROID CARCINOMA
Lima EU1; Tomimori EK2; Camargo RYA2; Domingues RB3; Marui S1 1
Laboratório de Endocrinologia Celular e Molecular/Unidade de Tireoide/
LIM 25/Faculdade de Medicina da Universidade de São Paulo (FM/USP);
2
Divisão de Endocrinologia/Unidade de Tireoide/Departamento de Clínica
Médica/Hospital das Clínicas da Faculdade de Medicina da Universidade de
São Paulo (FM/USP);3Departamento de Patologia do Hospital das Clínicas da
Faculdade de Medicina da Universidade de São Paulo (HC/FM/USP) Background: About 15%-20% of FNAB diagnoses are
Bethesda III-V and surgery is required for diagnosis.
BRAFV600E mutation was identified in 28%-83% of FNAB
diagnosed with Bethesda V and VI and showing a high concordance with the results obtained in tumor tissue, helps to
improve preoperative diagnosis as also surgical approach.
Objectives: To establish the prevalence of BRAFV600E in
FNAB material and correlate to clinical data and histopathologic agressiveness in patients submitted to thyroidectomy.
Methods: Mutation analysis was performed in cytological
slides of nodules diagnosed with Bethesda III-VI (n:224)
using Genotyping PCR and automatic-sequence for validation.Clinical, hormonal, autoimmunity, ultrasonography and
histological characteristics were evaluated. Results: Patients
were divided into benign (n:122) and malignant group
(n:102), according to histological diagnosis.Malignant group
had mean age lower (48.9 versus 54.2, p=0.008). There were
no differences between groups regarding TSH (p=0.467) and
autoimmunity. Size and volume of nodules at ultrasound
were higher in benign group (3.0 versus 2.6 cm and 12.4 versus 14.5cm3, p= 0.008 and p<0.001). Nodules with hypoechogenicity, solid, microcalcifications, absence of halo and central vascularization showed higher frequency of malignancy.
Older age,solid nodule without halo and microcalcifications
influenced jointly the presence of malignancy.78.6% (176/224)
of nodules were evaluated as Bethesda III-V, and 35.8%
(63/176) had final diagnosis of malignancy.BRAFV600E was
identified in FNAB 67.7% (69/102) of malignant group and
all findings were confirmed in excised tumor. Patients with
PTC (n:98) were compared according to presence of mutation
and only older age was significantly associated with the mutation (p=0.041). Vascular, capsular and linfonodal invasions
and histological type were not different between positive and
negative mutation. Conclusions: We identified BRAFV600E
in FNAB material at a high frequency.However it was not
associated with aggressiveness parameters, but older age.
Tables: Premio jovem investigador.pdf
Keywords: papillary thyroid carcinoma; FNAB; V600E mutation.
OR30 ALTA FRECUENCIA DE BRAF V600E EN CÁNCER
PAPILAR DE TIROIDES, ASOCIACIÓN CON MARCADORES
DE DIFERENCIACIÓN CELULAR Y PARÁMETROS CLÍNICOS
E HISTOLÓGICOS
Pineda P1; Osorio F1; Lanas A1; Cabané P2; Morales C3; Espinoza J4;
Tapia V4 1
Sección de Endocrinología del Hospital Clínico, Universidad de Chile;
2
Departamento de Cirugía, Hospital Clínico, Universidad de Chile;
3
Departamento de Anatomía Patológica, Hospital Clínico, Universidad de
Chile; 4Laboratorio de Endocrinología, Hospital Clínico, Universidad de Chile
Abstracts: Oral
Introducción: El Carcinoma Papilar (CP) es la neoplasia tiroidea más frecuente. La mutación BRAF V600E tiene frecuencia
variable y se asocia a evolución desfavorable, especialmente en
tumores con más alelos mutados. Objetivos: Determinar en
pacientes chilenos con CP la frecuencia de BRAF V600E y
su asociación con expresión de marcadores de diferenciación
celular y con parámetros clásicos de etapificación y pronóstico. Material y método: Se obtuvieron muestras de biopsia
rápida quirúrgica. Se extrajo DNA genómico y se detectó la
mutación por PCR Alelo Específico. En muestras seleccionadas, se confirmó la presencia o ausencia de BRAF V600E
por secuenciación. Se extrajo mRNA del tejido y cDNA por
transcripción reversa, y se analizó la expresión de 3 marcadores: NIS, Tiroglobulina (Tg) y GLUT-1, normalizados con
b-actina por PCR convencional. Resultados: Se montó un
protocolo de PCR con alta reproducibilidad. En 65 muestras
de CP analizadas, un 67,7% presentaba la mutación BRAF
V600E. En 14 muestras, controles de tiroides normal (TN) y
en 7 nódulos benignos no se detectó la mutación. En los CP
V600E (+) observamos bandas de amplificación de distinta
intensidad, que se explicarían por distintas proporciones de
alelos mutados. Los CP V600E (+) fueron agrupados según
intensidad arbitraria de amplificación en alta (A) y baja (B). En
análisis global CP V600E (+) v/s (-) solo encontramos diferencia en edad (43,7 v/s 34.9 años, p=0,0035). En subanálisis de
CP V600E (+) A v/s V600E (-) + V600E (+) B, hubo diferencias en edad (44,6 v/s 36,9 años, p=0,008) y en tamaño tumoral (19,8 v/s 13,6 mm, p=0,018). No hubo diferencias en otros
criterios clínicos ni histológicos. Para marcadores de diferenciación se analizó CP V600E (+), CP V600E (-) y TN, encontrando entre CP V600E (+) y TN, menor expresión de NIS
(0,9 v/s 1,46 Unidades Arbitrarias (UA), p=0,038) y Tg (0,52
v/s 1.16 UA, p=<0,005), y aumentada de GLUT-1 (1,45 v/s
0,99 UA, p=0,016). Conclusiones: Pesquisamos una elevada
frecuencia de CP V600E (+) en la población chilena. Los CP
V600E (+) son de mayor edad y tamaño tumoral, con evidencias de mayor desdiferenciación. Los CP V600E (+) son heterogéneos, lo que explicaría la falta de asociación con factores
pronósticos en el análisis global y lo que hace recomendables
los estudios de cuantificación de carga alélica. A partir de este
primer estudio nacional, proponemos estudios prospectivos y
multicéntricos que permitan precisar la relevancia pronóstica
de esta mutación en la población latinoamericana.
Palabras clave: thyroid cancer; BRAF; allele-specific PCR.
103

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