OBJETIVO: Estabelecer a frequência de U Tg (tireoglobulina indetectável pré-ablação) em pacientes com TgAb negativo e avaliar o prognóstico no seguimento. SUJEITOS E MÉTODOS: Foram analisados retrospectivamente 335 registros de pacientes. Vinte e oito pacientes (9%) tiveram U Tg. O acompanhamento médio foi de 42 ± 38 meses. Todos os participantes receberam uma tireoidectomia total, e os linfonodos foram positivos em 13 (46%) pacientes. Tg e TgAb foram medidos quatro semanas após a cirurgia pelo método IMA em estado de hipotireoidismo. A não evidência de doença (NED) foi definida como níveis indetectáveis (<1 ng/mL) de Tg estimulada com anticorpos anti-Tg negativos e/ou PCI negativo, com estudos de imagem normais. RESULTADOS: Dezessete pacientes (61%) foram considerados com NED. Quatro pacientes (14%) tiveram doença persistente (mediastino, n = 1, pulmão n = 2, n = desconhecido 1), e 7 (25%) apresentavam anticorpos anti-Tg detectáveis por outro método durante acompanhamento. CONCLUSÕES: U Tg geralmente indica uma cirurgia completa. No entanto, em uma pequena porcentagem de pacientes, pode estar relacionada com uma medida de Tg ou de anticorpos anti-Tg falsamente negativos.

OBJECTIVE: To establish the frequency of U Tg (undetectable pre-ablation thyroglobulin) in TgAb- negative patients and to evaluate the outcome in the follow-up. SUBJECTS AND METHODS: We retrospectively reviewed 335 patients' records. Twenty eight patients (9%) had U Tg. Mean follow-up was 42 ± 38 months. All subjects had undergone total thyroidectomy, and lymph nodes were positive in 13 (46%) patients. Tg and TgAb levels were measured 4 weeks after surgery by IMA technology in hypothyroid state. No evidence of disease (NED) status was defined as undetectable (< 1 ng/mL) stimulated Tg and negative Tg-Ab and/or negative WBS, together with normal imaging studies. RESULTS: Seventeen patients (61%) were considered with NED. Four patients (14%) had persistent disease (mediastinum, n = 1, lung n = 2, unknown n = 1), and 7 (25%) had detectable TgAb by other method during their follow-up. CONCLUSIONS: U Tg levels usually is associated to a complete surgery. However, in a low percentage of patients, this may be related to false negative Tg or TgAb measurement.

OBJETIVO: O objetivo deste estudo foi determinar se o câncer de tiroide não medular (CNMF) é mais agressivo do que o câncer esporádico de tiroide. SUJEITOS E MÉTODOS: Comparamos o comportamento clínico e a evolução de 16 portadores de CNMF de sete famílias não relacionadas com 160 CP (câncer papilífero) esporádicos de nosso serviço. RESULTADOS: As únicas diferenças nas características basais dos grupos eram: malignidade bilateral 38% vs. 24%, respectivamente (p = 0,03), e metástases linfonodais, 57,1% vs. 39%, respectivamente (p = 0,01). Em relação à evolução, 9 (56,2%) pacientes com CNMF ficaram livres de doença, um paciente faleceu devido ao CP (6%) e 6/16 (37,5%) apresentavam persistência da doença. No grupo de CP esporádicos, 87 (54%) foram considerados livres de doença, 11 (7%) morreram em decorrência do CP e 62 (38%) apresentavam persistência da doença (p = ns). CONCLUSÃO: Apesar da elevada incidência de metástases linfonodais nos pacientes com CNMF, essa situação não parece alterar a evolução dos dois grupos em longo prazo.

OBJECTIVE:The purpose of this study was to determine whether familial non-medullary thyroid cancer (FNMTC) is more aggressive than sporadic thyroid cancer. SUBJECTS AND METHODS: We compared the clinical behavior and outcome of 16 subjects with FNMTC from 7 unrelated kindred with those observed in 160 subjects with sporadic PTC (SPTC) from our database. RESULTS: The only different baseline characteristics observed between both groups were: bilateral malignancy, 38% vs. 24%, respectively (p = 0.03), and lymph node metastasis, 56.2% vs. 39%, respectively (p = 0.01). Considering the outcome, in the FNMTC, 9 (56.2%) patients were rendered free of disease, one patient died from thyroid cancer (6%), and 6/16 (37.5%) had persistent disease. In the SPTC Group, 87 (54%) patients were considered free of disease, 11 (7%) died due to PTC, and 62 (38%) had persistent disease (p = ns). CONCLUSIONS: Despite the higher incidence of lymph node metastasis in FNMTC patients this situation seemed not to alter the compared outcome.

In the familial form of papillary thyroid cancer (PTC), two or more members of the same family have to be affected with PTC. Prevalence is around 5% of all PTC. We performed a clinical analysis in 79 relatives of 16 patients of 7 unrelated kindred with the diagnosis of familial papillary thyroid carcinoma (FPTC). The results were compared with a control group. Thyroid palpation and TSH and TPO-Ab assessment was carried out in the relatives without a diagnosed PTC. Additionally, molecular analysis was performed in the sixteen affected patients. Clinical screening of the 79 family members showed the presence of goiter in 22/79 (29 %). This frequency was much higher than that observed in the control group (8.7%), p < 0.001. Hypothyroidism was found in 4 of the relatives (5%) vs. 2.5% observed in the control group, p < 0.01, and anti-thyroid antibodies (TPO-Ab) were positive in 14% of the relative's group vs. 10 % in the control group, (p = NS). In the molecular analysis, only a protooncogene TRK rearrangement was observed in family # 6. In conclusion, we found a higher incidence of goiter and hypothyroidism in the relatives of patients with FPTC. Nevertheless, TPO-Ab frequency was not different. No molecular abnormalities were indicative of a specific pattern in this subset of patients with FPTC.

En la forma familiar del carcinoma papilar de tiroides (CPT), dos o más miembros de la misma familia deben presentar CPT. Esta entidad ocurre en aproximadamente el 5% de todos los CPT. En este estudio, realizamos una evaluación de 79 familiares de 16 pacientes con diagnóstico de carcinoma papilar familiar (CPF) provenientes de 7 familias diferentes. Los resultados se compararon con los hallados en un grupo control. Se realizó palpación tiroidea y medición de TSH y anticuerpos anti-tiroperoxidasa (TPO-Ab) en todos los familiares. Además, se llevó a cabo el análisis molecular en los 16 sujetos que presentaban el diagnóstico de CPF. La evaluación de los 79 familiares de estos pacientes demostró la presencia de bocio en 22/79 (29%). Esta frecuencia fue mucho mayor que la observada en el grupo control (8.7%), p < 0.001. Se diagnosticó hipotirodismo en 4 familiares (5%) vs. 2.5%, observado en el grupo control, p < 0.01, y los TPO-Ab fueron positivos en 14% de los familiares vs. 10% del grupo control, (p = ns). En el análisis molecular, solamente se halló un rearreglo del protoncogen TRK en una de las 7 familias con CPF. En conclusión, hallamos una elevada prevalencia de bocio e hipotiroidismo en los familiares de pacientes con CPT. Sin embargo, la frecuencia de autoinmunidad no fue diferente. No se hallaron alteraciones moleculares distintivas en estos pacientes con CPF.

Vários consensos têm sido publicados acerca do diagnóstico e do tratamento de nódulos e câncer da tireoide. Entretanto, as recentes recomendações nem sempre são apropriadas para diferentes regiões ou países. O objetivo deste trabalho foi oferecer uma série de recomendações para a avaliação e conduta de pacientes portadores de nódulos tireoideos aplicáveis a todos os países da América Latina. O trabalho foi realizado por um comitê composto por 13 membros da Sociedade Latino-Americana de Tireoide envolvidos com pesquisa e manejo de pacientes portadores de nódulos e carcinoma diferenciado da tireoide, de diferentes centros médicos da América Latina. As recomendações foram estabelecidas, após consenso, utilizando as opiniões especializadas de cada membro e os princípios da medicina baseada em evidência. Após a primeira reunião do grupo, um primeiro documento foi elaborado e encaminhado a todos os membros para revisão. Posteriormente, o documento foi enviado aos membros da Sociedade Latino-Americana de Tireoide para avaliação, sugestões e comentários. A versão final, elaborada após refinada revisão de todos os autores, representa o estado da arte no diagnóstico e na conduta de nódulos tireoideos, aplicáveis a todos os países da América Latina.

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.

Estas recomendações tiveram por objetivo o desenvolvimento de diretrizes para avaliação e manejo de pacientes com câncer diferenciado da tiroide em países latino-americanos. Um painel composto por 13 membros da Sociedade Latino-Americana de Tireoide (SLAT) - que estavam envolvidos em pesquisas, e eram peritos no cuidado do paciente com câncer da tiroide e provenientes de diferentes centros médicos latino-americanos - utilizou os princípios da Medicina Baseada em Evidências para produzir esse consenso. Após uma primeira reunião, um texto inicial foi elaborado, baseado em evidências e opiniões dos especialistas do painel e, posteriormente, circulado entre os membros do painel, para revisão. Após a revisão, o documento foi enviado aos membros da SLAT para comentários e considerações e, finalmente, revisado e refinado pelos autores. As recomendações finais aqui apresentadas demonstram o estado da arte no manejo do câncer diferenciado da tireoide aplicadas aos países latino-americanos.

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries.

Due to the observation of a great number of patients having achrocordons, when they underwent fine needle biopsies for thyroid nodules, we decided to perform a prospective study to investigate the relationship between this finding and the presence of insulin resistance (IR), since achrocordons are commonly seen in hyperinsulinemic subjects. A total of 120 consecutive women, aged 18-35 yrs were studied. All subjects were also evaluated by thyroid ultrasound (US) for measuring thyroid volume and the presence of nonpalpable nodules. Basal and post-prandial serum insulin was measured in all of them, as well as the Homeostasis Model Assessment (HOMA). Subjects were divided in two groups: Group A, with achrocordons (n = 44) and Group B, without achrocordons (n = 76). Group A showed 24 patients (54.5%) with thyroid nodules, whereas Group B only 13 subjects (17.1%); p = 0.0087. When we considered, as having high normal thyroid volume, the glands weighting more than 16 grams by US, without nodules, it was found that 8/44 cases from Group A (18.6%) and 3/76 from Group B (3.9%) fitted in such category, p = 0.0076. In patients with nodules and/or bigger thyroids, IR was observed in 36/44 (81.8%) of Group A and 14/76 (18.4%) of Group B, p = 0.0069, while the overall prevalence of IR was 0.47 in Group A and 0.05 in Group B, p = 0.00094. It is concluded that patients with achrocordons have a higher prevalence of US-detected thyroid nodules and larger thyroid glands. Then, it may be beneficial to search for thyroid abnormalities in those subjects with skin tags.

Debido a la alta frecuencia de acrocordones en pacientes que concurrían a nuestro servicio para realizar punciones aspirativas de nódulos tiroideos, realizamos un estudio prospectivo para investigar la relación entre este hallazgo y la presencia de insulino resistencia (IR), dado que los acrocordones son frecuentemente observados en pacientes hiperinsulinémicos. Se incluyeron 120 pacientes consecutivas, con edades entre 18 y 35 años. Todas fueron evaluadas con una ecografía tiroidea para determinar su volumen y la presencia de nódulos no palpables. Se midió insulinemia basal y post prandial, así como el índice Homeostasis Model Assessment (HOMA). Las pacientes se dividieron en 2 grupos: Grupo A, con acrocordones (n = 44) y Grupo B, sin acrocordones (n = 76). En el Grupo A se encontraron 24 (54.5%) con nódulos tiroideos, mientras que el Grupo B, sólo 13 (17.1%); p = 0.0087. Cuando consideramos la presencia de una glándula tiroides de tamaño elevado pero dentro de los límites normales, medida por ecografía (peso mayor a 16 gramos sin nódulos), encontramos que 8/44 casos del Grupo A (18.6%) y 3/76 del Grupo B (3.9%) entraron en esta categoría, p = 0.0076. En aquellas pacientes con nódulos tiroideos o glándula tiroides de mayor tamaño, observamos IR en 36/44 (81.8%) del Grupo A y en 14/76 (18.4%) del Grupo B, p = 0.0069, mientras que la prevalencia total de IR fue del 0.47 en el Grupo A y del 0.05 en el Grupo B, p = 0.00094. En conclusión, las pacientes con acrocordones tuvieron mayor prevalencia de nódulos tiroideos detectados por ecografía, glándula tiroides de mayor tamaño y mayor proporción de insulino resistencia.

In some countries, in order to perform rhTSH-aided thyroid remnant ablation (TRA) after surgery, it is generally necessary to confirm that thyroidectomy has been almost complete. Otherwise, the nuclear medicine specialist will not administer a high radioiodine dose because it might be hazardous due to the possibility of thyroid remnant actinic thyroiditis. Considering this, it would be necessary to use two rhTSH kits (one for diagnostic purposes and the other one to administer the 131I dose). In this study, we used an alternative protocol for TRA with the use of one kit of rhTSH in twenty patients diagnosed with low risk papillary thyroid carcinoma. All patients had negative titers of anti-thyroglobulin antibodies. Successful thyroid remnant ablation was confirmed with an undetectable rhTSH stimulated thyroglobulin level (< 1 ng/ml) in all 20 patients between 8 to 12 months after radioiodine administration. The use of this protocol combining scintigraphy with the subsequent administration of a therapeutic dose following the administration of one kit of rhTSH would avoid the need of using 2 kits to perform the ablation and would decrease the costs associated with its use while significantly enhancing the quality of life of patients with thyroid cancer.

En algunos países, para realizar la ablación de los remanentes tiroideos con radioyodo después de la cirugía, generalmente se requiere confirmar que la tiroidectomía fue casi completa, ya que de otra manera el especialista en medicina nuclear no administrará una dosis elevada de radioyodo, considerando que esto puede ser dañino para el paciente debido a la posibilidad de generar una tiroiditis actínica. De acuerdo con esto, sería necesario administrar 2 kits de rhTSH (uno para diagnóstico y otro para la dosis de radioyodo). En este estudio, empleamos un protocolo alternativo para la ablación luego de la administración de un único kit (2 ampollas) de rhTSH en 20 pacientes con antecedentes de un carcinoma papilar de bajo riesgo. Todos los pacientes presentaban títulos negativos de anticuerpos anti-tiroglobulina. La ablación exitosa de remanente tiroideo se confirmó con un nivel no detectable de tiroglobulina (<1 ng/ml) al estímulo por rhTSH en los 20 pacientes, entre 8 a 12 meses luego de la ablación. El uso de este protocolo que combina la posibilidad de realizar un centellograma diagnóstico y la ablación luego del uso de un solo kit de rhTSH, facilita su empleo, disminuye los costos asociados, a la vez que permite una mejor calidad de vida de los pacientes con cáncer de tiroides.

Paciente de 29 anos foi encaminhada ao Hospital de Clínicas por causa de convulsões generalizadas. Apresentava hipertiroidismo tratado com metimazol (MMI). A ressonância magnética mostrava quatro lesões metastáticas cerebrais. Possuía bócio com nódulo frio e linfonodo palpável ipsilateral. Usando 5 mg de MMI, a paciente apresentava hipertiroidismo subclínico e TRAb = 47,8% (normal < 10%). A tomografia computadorizada também mostrava metástases pulmonares. A paciente foi submetida a tiroidectomia total com dissecção cervical modificada e recebeu dose acumulada de radioiodo de 700 mCi durante o período de dois anos. Foi analisado o DNA extraído de tecido emblocado em parafina do tumor, do linfonodo metastático e de tecido tiroidiano não-tumoral. Foram encontradas mutações pontuais em dois genes: uma substituição do genótipo selvagem CAA no códon 61 de /N-RAS/ por CAT, substituindo a glicina pela histidina (G61H) e uma substituição da seqüência normal GCC no códon 623 do gene TSHR por TCC, trocando a alanina pela serina (A623S). Não foram encontradas mutações no tecido não-tumoral. Estudos in vitro mostraram ativação constitutiva de TSHR. Já que esta mutação ativadora de TSHR foi incapaz de atingir o final da cascata PKA no tecido tumoral, sugere-se que um mecanismo de cross-signaling possa explicar o desvio da cascata do receptor de TSH para outra mais proliferativa, envolvendo MAPKinase e levando ao comportamento mais agressivo deste câncer papilífero.

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

A total of 305 ambulatory patients recruited at the Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, with autoimmune thyroid disease (AITD) were studied to search for associations between autoimmune thyroid disease and presence of serum markers of autoimmune diabetes mellitus. Screening for markers of pancreatic beta-cell autoimmunity was performed by radioligand binding assays (RBA) as follows: autoantibodies to glutamic acid decarboxylase (GADA) and proinsulin (PAA) were determined in all sera, whereas autoantibodies to protein tyrosine phosphatase (IA-2A) and insulin (IAA) were additionally measured in 200 sera randomly selected from the total collection. In addition, every GADA positive serum among the remaining 105 sera was systematically tested for the presence of IA-2A and IAA. In the cohort of 305 AITD patients 22 (7.2%) were previously diagnosed as type 1, type 2 or insulin-requiring type 2 diabetics. Ten of these patients presented serum marker positivity specific for β-cell autoantigens and 12 were marker negative. On the other hand, considering the majority of non-diabetic AITD patients (n=283), β-cell marker positivity was detected in 17 individuals (6.0%). The prevalence of autoimmune diabetes markers was much higher in the studied population than in the general population utilized as a control group, and GADA was the most frequent marker.

Se investigó la asociación entre enfermedad tiroidea autoinmune y la presencia de marcadores séricos de diabetes mellitus en 305 pacientes ambulatorios con enfermedad tiroidea autoinmune reclutados en la División Endocrinología. La búsqueda de marcadores de autoinmunidad contra las células beta pancreáticas se realizó por la técnica de unión de radioligandos (RBA) como se detalla a continuación: se determinaron autoanticuerpos contra la decarboxilasa del ácido glutámico (GADA) y proinsulina (PAA) en todos los sueros, mientras que los anticuerpos contra la proteína tirosina fosfatasa (IA-2A) e insulina (IAA) fueron medidos en 200 de estos sueros tomados al azar de la colección total. Además, en los restantes 105 pacientes, la presencia de IA-2A y IAA fue evaluada en todos los sueros positivos para GADA. Del grupo de 305 pacientes con enfermedad tiroidea autoinmune 22 (7.2%) fueron diagnosticados previamente como diabéticos tipo 1, tipo 2 o tipo 2 insulino-requirientes. Diez de ellos presentaron positividad para marcadores específicos de autoantígenos de célula β, en tanto 12 fueron negativos. Por otra parte, en 17 de los 283 pacientes (6.0%) con enfermedad tiroidea autoimmune y sin diagnóstico previo de diabetes, se detectó positividad para marcadores de célula β. La prevalencia de marcadores de autoinmunidad asociados a diabetes fue mayor en la población estudiada que en la población general usada como grupo control, siendo GADA el marcador más frecuente.