El cáncer diferenciado de tiroides: experiencia clínica frente a un panorama cambiante / Differentiated thyroid cancer: clinical experience in a changing scenario

Antecedentes: el cáncer de tiroides es el cáncer endocrino más frecuente, ha aumentado significativamente su incidencia y se han producido importantes cambios en su tratamiento. Objetivos: analizar una población de pacientes con cáncer diferenciado de tiroides tratados en el Hospital Universitario Austral, evaluar sus resultados y discutir las nuevas tendencias en su manejo. Material y métodos: revisión retrospectiva de una serie de 344 pacientes operados entre mayo de 2001 y mayo de 2015; se realizaron 331 tiroidectomías totales y 13 lobectomías, con linfadenectomía central en el 82% y lateral en el 9 %, según hallazgos clínicos o ultrasonográficos. El 80% correspondieron al sexo femenino y el 95% fueron carcinomas papilares. De acuerdo con TNM, el 65 % fueron T1, 41% T1a (microcarcinomas) y, según ATA, el 87 % tenían bajo riesgo de recurrencia. El 34 % de los vaciamientos centrales y todos los laterales presentaron metástasis ganglionares, y solo el 1,8% presentó metástasis a distancia. El 73% de los pacientes recibieron I131 en dosis de 30 a 150 mCi (milicurios). Resultados: la supervivencia global fue del 99,2% con seguimiento promedio de 40,2 meses, con 0,8% de hipoparatiroidismo definitivo y 0,8% de parálisis recurrencial definitiva. Conclusiones: 1) casi el 80% de la población operada correspondía a estadios tempranos con bajo riesgo de recurrencia, 2) más del 40% correspondió a microcarcinomas, 3) los resultados obtenidos son similares a los comunicados por centros de alto volumen, 4) las conductas terapéuticas coincidieron con las recomendaciones de las guías en vigencia y con las nuevas tendencias en el manejo del cáncer diferenciado de tiroides.

Background: Thyroid cancer is the most common type of endocrine cancer with an incidence that is significantly increasing and with important treatment changes. Objectives: The aim of this study was to analyze a population of patients with differentiated thyroid cancer treated at the Hospital Universitario Austral, evaluate the outcomes and discuss the new trends in thyroid cancer management. Material and methods: A series of 344 patients undergoing thyroid surgery between May 2001 and May 2015 were retrospectively reviewed: 331 total thyroidectomies and 13 lobectomies. Central lymph node dissection was performed in 82% of the cases and lateral lymph node dissection in 9%, based on clinical and ultrasound findings. Most patients were women (80%) and 95% were papillary thyroid cancers. According to the TNM classification, 65% were T1, 41% T1a (microcarcinomas) and 87% corresponded to the ATA low risk of recurrence category. Lymph node metastases were present in 34% of the central neck lymph nodes and in all the lateral lymph nodes dissected, and only 1.8% presented distant metastasis. Radioactive iodine was used in 73% of the patients in doses between 30 and 150 mCi. Results: Overall survival was 99.2% with a mean follow-up of 40.2 months; 0.8% presented permanent hypoparathyroidism and 0.8% of the patients presented permanent recurrent laryngeal nerve palsy. Conclusions: 1) almost 80% of the patients undergoing surgery corresponded to early stages of the disease with low risk of recurrence; 2) more than 40% were microcarcinomas; 3) the results obtained are similar to those reported by high-volume centers; and 4) the review of this experience is similar to that reported by current practice guidelines, and the therapeutic approaches are in line with the recommendations of the current practice guidelines and with the new trends in the management of differentiated thyroid cancer.

Diagnóstico clínico, ultrasonográfico y citohistológico del carcinoma diferenciado del tiroides / Clinical, ultrasonographic and cytohistological diagnosis of differentiated thyroid carcinoma

Introducción: el carcinoma diferenciado del tiroides representa la neoplasia maligna más frecuente en Endocrinología. Su presentación clínica y su diagnóstico se han modificado gracias a la disponibilidad de herramientas diagnósticas, tales como, el ultrasonido tiroideo y la biopsia aspirativa con aguja fina. Objetivos: describir las características clínicas, ultrasonográficas y citohistológicas de los pacientes intervenidos quirúrgicamente por enfermedad tiroidea maligna, y evaluar en ellos la prevalencia de hipocalcemia crónica y el valor de la hormona estimulante del tiroides. Métodos: se realizó un estudio descriptivo retrospectivo, en el cual se revisaron los informes consecutivos de Anatomía Patológica de todos los pacientes intervenidos quirúrgicamente por enfermedad tiroidea nodular en el Hospital General Provincial Camilo Cienfuegos en el periodo comprendido de enero de 2012 a diciembre 2014. La muestra estuvo conformada por 118 historias clínicas de pacientes operados por enfermedad tiroidea nodular que reunieron los criterios siguientes: datos clínicos, resultados según los criterios de Bethesda de la punción aspirativa con aguja fina, del ultrasonido del tiroides y la biopsia. A estos pacientes se les citó para una evaluación clínica y se les determinó en ayunas, la hormona estimulante del tiroides y en 2 días diferentes, la calcemia. Los pacientes fueron clasificados en portadores de: enfermedad tiroidea maligna (n= 39) y enfermedad tiroidea benigna (n= 79). Resultados: clínicamente solo el 15,4 por ciento de los pacientes con enfermedad tiroidea maligna presentaron dolor o molestia espontánea y/o a la palpación de la glándula del tiroides. La enfermedad tiroidea maligna se diagnosticó en todas las categorías del citodiagnóstico: I: 1/1 (100 por ciento), II: 8/83 (9,6 pòr ciento), III: 4/6 (66,7 por ciento), IV: 2/2 (100 por ciento), V: 18/20 (90 por ciento), VI: 6/6 (100 por ciento). El carcinoma papilar representó la neoplasia más frecuentemente diagnosticada (37/39 pacientes), el 33,3 por ciento de estos enfermos mostraron cifras de hormona estimulante del tiroides por encima de 2,0 mU/L, y hubo un 46,15 por ciento de hipocalcemia crónica. Conclusiones: el carcinoma papilar fue la neoplasia más frecuentemente diagnosticada en los pacientes operados por enfermedad tiroidea maligna. La mayoría de estos pacientes tuvieron un comportamiento subclínico, un tercio de valores no óptimos de la hormona estimulante del tiroides y una prevalencia alta de hipocalcemia crónica(AU)

ntroduction: differentiated thyroid carcinoma represents the most frequent malignant neoplasia in Endocrinology. Its clinical presentation and diagnosis have been modified thanks to the availability of diagnostic tools, such as thyroid ultrasound and fine needle aspiration biopsy. Objectives: to describe the clinical, ultrasonographic and cytohistological characteristics of patients undergoing surgery for malignant thyroid disease, and to evaluate in them the prevalence of chronic hypocalcemia and the value of the thyroid´s stimulating hormone. Methods: a retrospective descriptive study was carried out, in which consecutive reports of Pathological Anatomy of all patients surgically treated for nodular thyroid disease at Camilo Cienfuegos Provincial General Hospital in the period from January 2012 to December 2014 were reviewed. The sample consisted of 118 medical records of patients operated on for nodular-thyroid disease that met the following criteria: clinical data, results according to the Bethesda criteria of fine needle aspiration, thyroid ultrasound and biopsy. These patients were called for a clinical evaluation and they were indicated to be fasting. The patients were classified into carriers of: ETM (n=. 39) and benign thyroid disease (n= 79). Results: in clinical terms, only 15.4 percent of the patients with malignant thyroid disease presented spontaneous pain or discomfort, and / or during palpation of the thyroid glands. Malignant thyroid disease was diagnosed in all categories of cytodiagnosis: I: 1/1 (100 percent), II: 8/83 (9.6 percent), III: 4/6 (66.7 percent), IV: 2/2 (100 percent), V: 18/20 (90 percent), VI: 6/6 (100 percent). Papillary carcinoma represented the most frequently diagnosed neoplasm (37/39 patients); 33.3 percent of these patients showed thyroid stimulating hormone levels above 2.0 mU / L, and there was 46.15 percent of chronic hypocalcemia. Conclusions: papillary carcinoma was the most frequently diagnosed neoplasm in patients operated of malignant thyroid disease. The majority of these patients had a subclinical behavior, a third of non-optimal values of the thyroid stimulating hormone and a high prevalence of chronic hypocalcemia(AU)

Guía práctica para el manejo de efectos adversos por inhibidores multicinasas (sorafenib y vandetanib) en pacientes con cáncer de tiroides avanzado / Practice guidelines for the management of adverse effects due to multikinase inhibitors (sorafenib and vandetanib) in patients with advanced thyroid cancer

El advenimiento de la terapia con inhibidores multicinasas (IMK) representó un cambio radical en el tratamiento de pacientes con carcinoma avanzado de tiroides. Hasta la fecha, 2 fármacos se encuentran aprobados por la Asociación Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) en Argentina: sorafenib, para pacientes con carcinoma diferenciado de tiroides radiorresistente, y vandetanib, para aquellos con carcinoma medular de tiroides (enfermedad progresiva y/o sintomática). Los estudios de fase III han demostrado que estos fármacos aumentan significativamente la supervivencia libre de progresión en este grupo de pacientes. Si bien tienen una indicación precisa, su manejo requiere de un equipo multidisciplinario en contacto estrecho con un paciente involucrado en su tratamiento. Los efectos adversos de sorafenib y vandetanib son frecuentes, sin embargo, muchos de ellos disminuyen con el tiempo y la mayoría puede manejarse a menudo sin disminuir la dosis ni suspender el fármaco. El conocimiento del correcto manejo de los efectos adversos por parte del equipo tratante constituye una herramienta fundamental para poder educar al paciente y, consecuentemente, poder prevenirlos o minimizarlos, y de esta manera evitar complicaciones severas. El objetivo de esta publicación es brindar una guía para el diagnóstico y tratamiento de los efectos adversos de estos IMK y, por otro lado, presentar la iniciativa del Hospital de Clínicas de la Universidad de Buenos Aires en cuanto a la implementación de la misma.

The advent of multikinase inhibitors therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The ANMAT (the Argentinian regulatory health agency) has currently approved sorafenib for patients with radioiodine resistant differentiated thyroid carcinoma, and vandetanib for patients with medullary thyroid carcinoma (progressive and/or symptomatic disease). It has been demonstrated by phase III clinical trials that these drugs improve progression free survival in this group of patients. Although they have a precise indication, an interdisciplinary team in close contact with a committed patient, are required for their effective management. The adverse events of these drugs are common, but many of them may ameliorate over time, and most of them are manageable, even without the need for dose reduction or drug withdrawal. Knowledge of the correct management of the adverse events is a fundamental tool for the medical team and for the patient to prevent or minimise them, to avoid serious complications and to obtain better patient compliance. The primary objective of this article is to provide a guideline for the diagnosis and treatment of the adverse events produced by the multikinase inhibitors, and to present the initiative of the Hospital de Clinicas in order to implement these guidelines.

Factores Pronósticos Determinantes de la Sobrevida del Cáncer Diferenciado de Tiroides en el Servicio de Cirugía de Cabeza y Cuello del Hospital Carlos Andrade Marín (HCAM) durante los años 1980 al 2010 / Decisive prognosis factors of survival of differentiated thyroid cancer in the Head and Neck Surgery Department of the Carlos Andrade Marin Hospital (HCAM) during the years 1980 - 2010

Introducción: El cáncer diferenciado de tiroides (CDT) constituye el 80% de los casos de enfermedad maligna de la glándula tiroides. Tiene buen pronóstico y evolución benigna. Varios estudios señalan que factores del paciente y del tipo de tumor influyen en su curso clínico. El objetivo de esta investigación fue determinar la sobrevida de los pacientes con CDT e identificar factores pronóstico. Materiales y Métodos: Se realizó un estudio descriptivo, retrospectivo de pacientes con CDT que acudieron al servicio de Cirugía de Cabeza y Cuello del Hospital Carlos Andrade Marín (HCAM) durante los años 1980 al 2010 y fueron sometidos a cirugía. Se evaluaron variables demográficas, variables dependientes del tumor y tipo de tratamiento. Se utilizó el método de Kapplan Meier para calcular las curvas de sobrevida y la prueba de Log Rank test para establecer su significancia. El modelo de Cox se utilizó para evaluar factores pronóstico. Resultados: De 353 pacientes estudiados, la sobrevida global a 5 años en el tipo folicular fue 65.4% y en el papilar 90.1%; a 10 años, el tipo folicular fue 41.5% y el papilar 76.9%; a 15 años, el tipo follicular fue 33.2% y el papilar 66.5%. El análisis univariado demostró diferencias significativas para factores como edad (p 0,002), extension extratiroidea (EET) (p 0,001) y ganglios cervicales invadidos (p 0,002). Discusión: La edad, la EET y la presencia de ganglios cervicales invadidos fueron factores pronósticos de la sobrevida de pacientes con CDT.

Abstract Introduction: Differenciated thyroid carcinoma (DTC) stand for 80% of malignant disease of the thyroid gland. DTC generally has a good prognosis and benign course. Several studies concluded that specific patient risk factors and tumor type determine their clinical course. The aim of the study was to define global survival and identify risk factors. Methods: We performed a descriptive and retrospective analysis of DTC patients who were surgically treated at the Head and Neck Surgery Service at Carlos Andrade Marin Hospital from 1980 to 2010. Demographic variables, tumor related variables and type of tumor were recorded. Kaplan Meier survival curves and long Rank test were obtained. Cox model was used to assess prognostic factors. Results: Of 353 DTC treated patients, the 5-year overall survival rate for follicular type was 65.4% and for papillary type 90.1%. A 10-year overall survival rate for follicular type was 41.5% and for papillary tipe 76.9 %. Finally, a 15-year overall survival rate for follicular type was 33.2 % and for papillary type 66.5%. Univariate analysis showed that factors like age (p 0,002), ETE ( p 0,001) and histological lymph node invasion (p 0,002) were significant. Discusion: Variables like age, ETE and histological lymph node invasion were found to be significant prognostic survival factors in DTC patients.

Cáncer diferenciado de tiroides de tipo folicular en la infancia y adolescencia: A propósito de un caso / Diferentiated thyroid cancer type folicular in childhood and adolescence: A case report

Objetivo: Presentación de un caso clínico de carcinoma folicular de tiroides en un adolescente, patología infrecuente en la población pediátrica y revisión de su manejo. Caso clínico: Paciente masculino de 14 años de edad que consultó por presentar aumento de volumen en región anterior del cuello de rápido crecimiento, 3 meses de evolución, asociado a dolor persistente, disfonía y disfagia. Examen físico: Peso: 65 kg, Talla: 1,68 m, IMC: 23 kg/m². Macrocefálico. Glándula tiroides aumentada de tamaño: 3x4 cm (3N), a expensas de lóbulo derecho, de consistencia aumentada y superficie lisa. No se palparon adenopatías. El ultrasonido (US) tiroideo reportó nódulo que midió 33 x 33 x 32 mm en el lóbulo derecho. Funcionalmente eutiroideo. El estudio citológico del nódulo mediante PAAF reportó neoplasia folicular. En abril del 2014 se le practicó tiroidectomía total, cuya biopsia reportó carcinoma folicular de tiroides mínimamente invasivo, de 4,7 x 4,6 x 3,8 cm. Esta neoplasia se clasificó como T3N0M0 (St I AJCC 2010 <45años), bajo riesgo de recurrencia (ATA 2009), se administró terapia metabólica con yodo radiactivo (150mCi). Conclusión: El riesgo de recurrencia estimado concuerda con las características del bajo riesgo, sin embargo se decidió el manejo terapéutico tomando en cuenta el tamaño de la lesión (mayor de 4 cm) y la agresividad que muestra el cáncer diferenciado de tiroides en éste grupo etario, donde se observa con mayor frecuencia multifocalidad, invasión a la cápsula y metástasis a ganglios linfáticos regionales o a distancia, al momento del diagnóstico.

Objective: To present a case of follicular thyroid carcinoma in an adolescent, uncommon condition in the pediatric population and management review. Clinical case: Male patient 14 years old who consulted for filing increased volume in anterior neck of rapid growth, 3 months of evolution associated with persistent pain, dysphonia and dysphagia. Physical exam: Weight: 65 kg, Height: 1.68 m, BMI 23 kg/m². Macrocephalic. Enlarged thyroid gland size: 3x4 cm (3N) at the expense of right lobe, increased consistency and smooth surface. No lymph nodes were palpated. Ultrasound (US) reported thyroid nodule that measured 33 x 33 x 32 mm in the right lobe. Functionally euthyroid. The cytological study of the nodule FNA reported follicular neoplasm. In April 2014 he underwent total thyroidectomy whose biopsy reported minimally invasive follicular thyroid carcinoma, 4.7x 4.6x 3.8 cm. This neoplasm was classified as T3N0M0 (St I AJCC 2010 <45 years), low risk of recurrence (ATA 2009). Metabolic radioiodine therapy (150 mCi) was administered. Conclusion: The estimated risk of recurrence is consistent with the characteristics of low risk, however the therapeutic management was decided taking into account the size of the lesion (greater than 4 cm) and aggressivity that shows the differentiated thyroid cancer in this group of age where more frequently is observed multifocality, invasion of the capsule and metastasis to regional lymph nodes or distant, at diagnosis.

Development, characterization and clinical validation of new sensitive immunofluorometric assay for the measurement of serum thyroglobulin / Desenvolvimento, caracterização e validação clínica de um novo ensaio sensível para a dosagem da tiroglobulina sérica

OBJECTIVE: In the last decade, data published stressed the role of highly-sensitive thyroglobulin (Tg) assays in the follow-up of differentiated thyroid carcinoma (DTC) patients. The present study describes a new, highly-sensitive Tg assay, compares it with an available commercial assay, and validates it in the follow-up of DTC patients. SUBJECTS AND METHODS: The immunofluorometric high-sensitivity Tg assay is based on monoclonal and polyclonal antibodies produced at our laboratories. It was validated in 100 samples of 87 patients with DTC submitted to total thyroidectomy, 87% of whom also received radioiodine. For correlation, all samples were also tested using a commercial Tg assay (Beckman Access) with functional sensitivity (FS) of 0.1 ng/mL. RESULTS: The new method showed FS of 0.3 ng/mL. The correlation between the two methods was good (r = 0.74; p < 0.0001). The diagnostic sensitivity was 88.9%, and it was increased to 100% when combined with neck US. CONCLUSION: This new, high-sensitivity Tg assay presented a good correlation with Beckman Access assay and with the clinical outcome of the patients. The continuous availability of a validated assay is an additional advantage for long term follow-up of DTC patients. Arq Bras Endocrinol Metab. 2012;56(9):658-65.

OBJETIVO: Na última década, estudos mostraram a importância dos ensaios de tiroglobulina (Tg) com melhor sensibilidade funcional no seguimento dos pacientes com carcinoma diferenciado de tiroide (CDT). Neste estudo, descrevemos o desenvolvimento de um novo ensaio de Tg de alta sensibilidade, que foi validado no seguimento de pacientes com CDT e correlacionado com um ensaio comercialmente disponível. SUJEITOS E MÉTODOS: O ensaio imunofluorométrico de Tg baseia-se em anticorpos, um monoclonal e um policlonal desenvolvidos em nosso laboratório. Avaliamos 100 amostras de soro de 87 pacientes com CDT submetidos à tiroidectomia total, sendo que 87% deles também receberam 131I. A Tg foi dosada também em ensaio comercial (Beckman Access). RESULTADOS: A correlação entre os dois métodos foi de 0,74 (p < 0,0001). O novo ensaio mostrou uma sensibilidade funcional de 0,3 ng/mL. A sensibilidade diagnóstica foi de 88,9%, que aumentou para 100% quando associada ao ultrassom cervical (US). CONCLUSÃO: O novo método de dosagem de Tg mostra boa correlação com o ensaio comercial Beckman Access e com a evolução clínica dos pacientes. O novo ensaio será fundamental no seguimento dos nossos pacientes com CDT. Arq Bras Endocrinol Metab. 2012;56(9):658-65.

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop / Doses cumulativas de iodo radioativo no tratamento do carcinoma diferenciado de tireoide: sabendo a hora de parar

OBJECTIVE: Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: The probability of progressive disease according to CDs was evaluated in patients < 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. RESULTS: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs > 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. CONCLUSION: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.

OBJETIVO: Avaliar a eficácia de doses cumulativas (DCs) da terapia com iodeto-131I (RIT) no câncer diferenciado de tiroide (CDT). SUJEITOS E MÉTODOS: A probabilidade de doença em progressão conforme a DC foi calculada em pacientes com idade < 45 e > 45 anos e correlacionada com o TNM, valores de tiroglobulina sérica, tipos histológicos e variantes, idade e tempo de doença. RESULTADOS: Ao final de um seguimento de 69 ± 56 meses, 85 dos 150 pacientes CDT submetidos a doses fixas de RIT não tinham evidência de doença, 47 tinham doença estável e 18, doença progressiva. DCs mais elevadas foram usadas nas variantes agressivas (p < 0,0001), maior estágio TNM (p < 0,0001) e nos carcinomas foliculares (p = 0,0034). A probabilidade de doença em progressão foi maior com DCs > 600 mCi em pacientes > 45 anos e com DCs > 800 mCi em pacientes < 45 anos. CONCLUSÃO: Apesar de alguns pacientes ainda responderem a altas DCs, o impacto de RITs deve ser cuidadosamente avaliado e outras estratégias terapêuticas devem ser consideradas.

Carcinoma diferenciado de tiroides (CDT) en niños y adolescentes: Evolución clínica y factores pronósticos / Differentiated thyroid carcinoma in children and adolescents: Clinial outcome and prognostic factors

Si bien la forma de presentación del CDT es más agresiva en la edad pediátrica que en los adultos, la tasa de sobrevida es superior al 90%.Objetivo: analizar retrospectivamente las características clínico-patológicas,la evolución y los factores pronósticos en pacientes prepuberales (PP) y puberales (P) con diagnostico de CDT controlados en nuestro servicio. Resultados se incluyeron 43 pacientes seguidos por un tiempo X (±DS) de 5.99 años(a) (3.57) a, rango 1 -14 a. El tratamiento consistió en tiroidectomía con vaciamiento ganglionar, Iodo131 y levotiroxina en dosis inhibitoria de TSH. Al diagnóstico: edad cronológica (EC) X (±DS)10.9 (3.84) a, rango: 4.7 -17a, relación femenino /masculino 2.9. Diecinueve PP y 24 P. El 53.5% (n:23) presentó nódulos confinados a la glándula con o sin extensión ganglionar y el 46.5% (n:20) tenia un estadío tumoral más avanzado con invasión local y metástasis (MTS) pulmonar. Treinta y ocho pacientes (88.4%) tenían MTS ganglionar cervical y 16(37.2%) MTS pulmonar. El grupo PP comparado con el P tenía EC significativamente menor X (±DS) 7.25 (2.03) a vs 13.83a (p <0.001), estadío tumoral más avanzado 84.2 vs16.8% (p<0.001) y mayor ocurrencia de MTS pulmonar 68.4 vs 12.5% (p<0.003). La sobrevida global fue de 92% y libre de enfermedad 78%.Las variables predictoras de persistencia de enfermedad más significativas fueron presencia de MTS pulmonar al diagnóstico y niveles séricos de tiroglobulina superiores a 8.5 ng/ml posterior al tratamiento inicial. Conclusión: el CDT pediátrico tiene una presentación agresiva especialmente en los pacientes prepuberales. El pediatra debería incorporar el examen clínico del cuello para realizar un diagnóstico y tratamiento precoz (AU)

Children-DTC has been found to behave differently than in adults. At diagnosis, children present in a more aggressive way. However the overall survival rates is greater than 90%. The aim of this study was to perform a retrospective analysis of clinicopathologycal features at diagnosis, evolution and prognostic factors for DTC in pre-pubertal (PP)and pubertal (P)children treated at our centre. Results: 43 CDT patients were included. Mean follow up was X (±DS) 5.99 (3.57) years (y) range: 1 -14 y. Treatment consisted on total thyroidectomy with lymph node dissection, radioiodine therapy, and TSH suppressive therapy with L-thyroxine. At diagnosis: chronological age (CA) was (±DS) :10.9 (3.84) y, range: 4.7 - 17y,sex: female/male ratio: 32/11,nineteen were PP and 24 P. Twentythree ( 53.5%) presented intrathyroidal nodes with or without lymph node MTS, Twenty patients (46.5%) had advanced disease, with adjacent tissue invasion and lung MTS. Thirty-eight patients (88.4%) had cervical lymph node MTS, 16 (37.2%) lung MTS.PP group had significant less CA X (±DS) 7.25 (2.03) y vs 13.83 (1.95)y (p <0.001),advanced tumor stage 84.2 vs16.8% (p<0.001) and more lung MTS occurrence 68.4 vs 12.5% (p<0.003). Global survival rate was 92% and disease free survival rate was 78%.Lung metastases (MTS) and serum thyroglobuline levels greater than 8.5 ng\ml post initial treatment were the most significant prognostic factor related to persistent disease. Conclusion: CDT had a more aggressive presentation in children; especially in PP children. Pediatricians should be aware of this in order to realize a precocious diagnosis and treatment (AU)

Carcinoma diferenciado da tiroide / Differentiated thyroid carcinoma

O carcinoma diferenciado da tiroide (CDT) é a neoplasia endocrinológica mais comum. Nos Estados Unidos da América do Norte se estimam que 33.000 pessoas sejam acometidas pela doença. Nos últimos anos se tem observado um aumento progressivo no número de casos por ano em todo o mundo. O CDT tem usualmente uma sobrevida acima de 90% em dez anos, todavia, aproximadamente 20% dos pacientes podem cursar com recorrências locais e a distância, aumentando a mortalidade pelo tumor e reduzindo o tempo livre de doença. Por esses motivos a correta classificação dos indivíduos com CDT, torna-se imprescindível para oferecer o melhor e mais adequado tratamento.

Utilidade da tomografia de emissão de pósitrons com fluoro-deoxiglicose (FDG-PET) na avaliação do câncer de tireóide: uma revisão sistemática / Utility of positron emission tomography with fluorodeoxyglucose (FDG-PET) in the evaluation of thyroid cancer: a systematic review

Após o tratamento inicial do câncer tireoidiano, a detecção de prováveis recorrências e/ou metástases se faz através da dosagem de marcadores séricos e estudos de imagem. Essas técnicas podem ser negativas apesar de evidências bioquímicas de doença metastática. A tomografia de emissão de pósitrons com fluorodeoxiglicose (FDG-PET) tem sido proposta como um teste acurado para detectá-la. O objetivo deste estudo é apresentar uma síntese das evidências obtidas através de revisão sistemática sobre a acurácia do FDG-PET na localização de metástases de câncer tireoidiano previamente tratado, nos quais as modalidades convencionais falharam na sua detecção. Foi realizada uma pesquisa bibliográfica no MEDLINE de todos os trabalhos relativos a FDG-PET e carcinoma tireoidiano diferenciado, indexados até setembro de 2005. Foram obtidas 216 citações e 17 trabalhos foram incluídos, 71 por cento publicados a partir de 2000. A sensibilidade da FDG-PET foi elevada, com apenas um trabalho apresentando sensibilidade inferior a 75 por cento. A especificidade, examinada em 12 estudos, foi menor que 75 por cento em 3 estudos. Em 41 por cento dos trabalhos existia pelo menos um teste comparativo com o FDG-PET. Os resultados apontam o FDG-PET como um teste diagnóstico útil para a detecção e localização de metástases do câncer tireoidiano, com implicações diretas no tratamento dos pacientes.

After the initial thyroid cancer treatment, the detection of likely recurrences and/or metastases is made through the measurement of serum markers determinations and diagnostic image procedures. These techniques may be negative in spite of biochemical evidence of metastatic disease. The positron emission tomography with fluorodeoxyglucose (FDG-PET) has been proposed as an accurate method to detect it. The aim of this study is to present a synthesis of the evidences obtained from a systematic review regarding FDG-PET accuracy in locating suspected metastases of previously treated thyroid cancer, when the conventional methods failed to do it. A bibliographic review of all studies related to FDG-PET and differentiated thyroid cancer was made on MEDLINE, indexed until September 2005. Two hundred and sixteen citations were collected and 17 studies included, 71 percent were published after 2000. FDG-PET sensibility was high, with only one study presenting a sensibility lower than 75 percent. The specificity, examined in 12 studies was lower than 75 percent in 3 studies. There was at least one test compared to FDG-PET in 41 percent of the studies. The results point to FDG-PET as a useful diagnostic test to detect and localize thyroid cancer metastases, with direct implications in the treatment of these patients.

O ensaio de tiroglobulina com melhor sensibilidade funcional enquanto os pacientes tomam L-T4 substituirá a tiroglobulina estimulada pelo TSH no seguimento dos pacientes com câncer diferenciado da tiróide? / Will the thyroglobulin assay with lower functional sensitivity whilst the patients are on L-T4 treatment replace the TSH-stimulated thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer?

O autor apresenta evidências recentes da literatura que mostram que ensaios de tiroglobulina sérica (sTg) com maior sensibilidade funcional apresentam a mesma qualidade que a obtenção da sTg estimulada por rhTSH ou hipotiroidismo, no seguimento de pacientes com câncer diferenciado de tiróide (CDT). Desta forma, propõe modificar a prática recomendada pelas diretrizes de sociedades internacionais para o seguimento desses pacientes (desenvolvidas enquanto os ensaios disponíveis apresentavam sensibilidade de 1 ng/mL), substituindo-se a obtenção da sTg estimulada por rhTSH ou hipotiroidismo pelo acompanhamento dos pacientes na vigência da terapia com L-T4 com a medida da sTg desde que se empreguem técnicas com sensibilidade funcional da ordem de 0,1-0,2 ng/mL.

The author reviews the literature on the new assays for serum thyroglobulin (sTg) presenting lower functional sensitivity and demonstrates that its use, whilst the patients are taking L-T4, presents better results than sTg following TSH stimulation in the follow-up of patients with differentiated thyroid carcinoma. Therefore, he suggests a revision on the guidelines for the follow-up of these patients (developed when the available assays present a sensitivity of 1 ng/mL), proposing the use of sTg assays with functional sensitivity of 0.1-0.2 ng/mL with the patients on L-T4 treatment instead of sTg stimulated by TSH.

Nódulos de tireóide e câncer diferenciado de tireóide: consenso brasileiro / Thyroid nodules and differentiated thyroid cancer: brazilian consensus

Os nódulos tireoidianos constituem a principal manifestação clínica de uma série de doenças da tireóide com uma prevalência de aproximadamente 10 por cento na população adulta. O maior desafio é excluir o câncer da tireóide, que ocorre em 5 a 10 por cento dos casos. Os carcinomas diferenciados respondem por 90 por cento dos casos de todas as neoplasias malignas da tireóide. A maioria dos pacientes com carcinoma diferenciado apresenta, geralmente, um bom prognóstico quando tratada adequadamente, com índices de mortalidade similares à população geral. No entanto, alguns indivíduos apresentam doença agressiva, desafiando o conhecimento atual e ilustrando a complexidade do manejo dessa neoplasia. No presente trabalho, reunimos 8 membros do Departamento de Tireóide da Sociedade Brasileira de Endocrinologia & Metabologia, para elaborarmos, por consenso, as diretrizes brasileiras no manejo dos nódulos tireoidianos e do câncer diferenciado da tireóide. Os membros participantes representam diferentes Centros Universitários do Brasil, refletindo diferentes abordagens diagnósticas e terapêuticas. Inicialmente, cada participante ficou responsável pela redação de determinado tema a ser enviado ao Coordenador, que, após revisão editorial e elaboração da primeira versão do manuscrito, enviou ao grupo para sugestões e aperfeiçoamentos. Quando concluído, o manuscrito foi novamente enviado e revisado por todos. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão pertinente da literatura.

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10 percent of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10 percent). Differentiated thyroid carcinoma accounts for 90 percent of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

Estimulación iterativa (EI) de TSH endógena (TSH-En) mediante el uso de la hormona liberadora de tirotrofina (TRH) en pacientes portadores de carcinoma diferenciado de tiroides / Rapid iterative stimulation (IS) of endogenous tsh (En-TSH) utilizing thyrotropin releasing hormone (TRH) in patients with differentiated thyroid carcinoma (DTC)

En el CDT es indispensable elevar los valores de TSH para efectuar Tg y barrido (RCT) con 131I, debiéndose suspender la opoterapia (HT) durante 4/5 sem. con el consecuente hipotiroidismo (H) y los trastornos que conlleva. Nuestro objetivo fue incrementar en forma rápida TSH-E acortando el tiempo de abstinencia. Se efectuaron 43 estudios en 37 pacientes con CDT (G-1); de entre 19 y 78 años, 34 con forma papilar y 3 folicular de CDT, 12 de sexo masculino y 25 femenino Se consideraron 2 subgrupos, G-1A, 7 p. para ablación (A); G-1B, 36 p. para seguimiento (S) y/o tratamiento (T) entre 6 meses y 5 años poscirugía; 6 p. efectuaron dos estudios, 4 para A y S y 2 para 2 veces S. Como comparación se revisaron 41 estudios en 35 p (G-2) que efectuaron suspensión de opoterapia por 4/5 semanas, entre 18 y 81 años; 28 de sexo femenino y 7 masculino; 32 papilares y 3 foliculares; 18 para A (G-2 A) y 21 para S, primer control (G-2B); 4 p. efectuaron 2 estudios, A y S. G-1A: entre 8/10 días poscirugía se les administra TRH 200 mcg i.v los días 1, 3, 5 y 6. A los 30 min de la 3ra aplicación, determinación de TSH y RCT con 370 MBq de 99mT; a igual lapso en la 4ta aplicación determinación de TSH, Tg y antiTg y 5,55 o 7,4 GBq de 131I, para A; a los 8 días RCT con 131I. G-1B: se suspende T4 y reemplaza por T3 por 3 semanas. Se suspende T3; a las 24 horas se inicia el esquema indicado para G-1A . A la 4ta aplicación de TRH, se administra el 131I, 14,8 MBq y RCT a las 48 horas en S o la actividad terapéutica indicada para T. En ambos grupos se indicó dieta hipoyódica. Resultados: En G-1, los valores de TSH ascendieron a 26-360 UI/L; promedio 83 UI/L ± 54; G-1A : 137 ±109; G-1B 7, 62 ± 52 . Los RCT no mostraron diferencias con ambos trazadores. En G-1A todos los p presentaron remanentes tiroideos y Tg positivas. En G-1B, 21 p. mostraron RCT y Tg negativas; 7 áreas activas y Tg positivas y 8 p RCT negativos con valores elevados de Tg . En G-2, TSH, 23-170 UI/L ( 63 ± 3 UI/L) ; G-2 A: 71 ± 41 ; G-2B, 63 ± 42. Conclusiones: Estos hallazgos indican que a) la metodología propuesta es adecuada para acortar sensible-mente el tiempo de abstinencia de opoterapia y reducir la sintomatología del H que pasa desapercibida en la mayoría de los casos; b) los valores de TSH-En obtenidos son similares y aun superiores a los alcanzados por suspensión de opoterapia por lapsos prolongados; c) el empleo del RCT con 99mTc como indicador de tejido captante disminuye el uso terapéutico a ciegas de 131I al señalar casos de ausencia de concentración y permite, cuando sea necesario, obtener anticipadamente 131I para su empleo terapéutico.

In the follow up (F) of p with DTC it is necessary to obtain high figures of serum TSH for determination of serum Tg and 131I scan (WBS). For this object, he method, for a long time, was to withdrawal thyroid hormone therapy (generally l-T4) that produce hypothyroidism with the inconvenient for the p, dramatics in certain cases. Our objective was to increase TSH by IS to shortening time of L-T4 withdrawal for F, ablation (A) or treatment (T) with 131I. In 37 p. with DTC (G-1), aged 19-78 y., 34 with pap. DTC and 3 with foll. form, 25 females, 12 males, 43 studies were carried out; 6 p carried 2 studies. The group was divided in 2 sub-groups: G-1A,7 p derived for A; G-1 B 36 p. for F or T with 131I. Six p carried out 2 studies; 4 of them for A and for F and 2 realizes 2 times F. All p treated with l-T4 replaced this hormone for T3 during 3 weeks ,that was withdrawal the day before IS. In G-1A, between 8/10 days after surgery they begin IS. IS: At days 1, 3, 5 and 6, the p were injected i.v. with 200 mcg of TRH; at 30 minutes of the 3rd injec. blood TSH determination ; immediately 370 MBq of 99mT was administered and at 30 minutes a WBS was carried out. At 30 minutes of the 4th injec. blood figures of TSH, Tg and Tg-ab were determined; immediately the activity of 131I indicated for each group was given to the p; in G-1A, at 8 days and in G1-B, at 48 hours WBS were carried out. As a control group (G-2) 41 studies in 35 DTC p. that withdrawal l-T4 for 4/5 weeks, were studied, aged 18-81 years, 31 females and 4 males; 32 with pap. and 3 folli.c form; 18 for A (G-2A) and 23 for F (G-2B); 6 p carried out 2 studies. One for A and the second as the first control. In G-1, TSH values obtained were 26-360 UI/L ( 83 ± 54. In G-1A : 137 ± 109 and in G-1B 62 ± 52). The 2 tracers 131I and 99mTc-Tc, produce show similar figures. In G-1A all p present thyroid remnants and elevated Tg. In G-1B, 7 p showed positive WBS and Tg; 8 p present Tg positive and WBS negative and 21 WBS and Tg negative. In G-2, the TSH values obtained were 23-179 UI/L (63 ± 39 ); G-2A 71 ± 41 and G-2B 63 ± 42. These findings indicate that the methods is adequate to shortened the time of withdrawal of l-T4 and reduce the signs/symptoms of hypothyroidism to an acceptable status. Also allow us to considered the use of 99mTc as an indicator of existence of remnants, relapses or metastases and avoid blind use of therapeutic activities of 131I.

Valor da dosagem da tireoglobulina no seguimento de pacientes com carcinoma diferenciado da tireóide submetidos à tireoidectomia parcial / Value of serum thyroglobulin measuremat in the follow-up of patients with differentiated carcinoma treated by partial thyroidectomy

OBJETIVO: Estudar o valor da dosagem da tireoglobulina (Tg) plasmática na detecção de recidivas, nos pacientes com carcinoma diferenciado da tireóide, submetidos à tireoidectomia parcial. MÉTODOS: São analisados, retrospectivamente, 48 pacientes portadores de carcinoma diferenciado e submetidos à tireoidectomia parcial que foram acompanhados no pós-operatório com dosagens de Tg plasmática. O exame foi realizado no paciente com TSH suprimido (< 0,6mU/cc) e o valor da Tg de 10ng/cc considerado como limite entre os casos com e sem suspeita de recidiva. O tempo médio de seguimento foi de 8,1 anos. RESULTADOS: Onze pacientes apresentaram Tg elevada (> 10ng/cc) e quatro eram portadores de doença benigna capaz de elevar a Tg como hipertireoidismo (dois casos) e doença de Hashimoto (dois casos). Estes quatro pacientes não foram considerados na análise estatística. Os sete restantes foram considerados suspeitos de recidiva tumoral que foi confirmada em seis (verdadeiro positivo) e não confirmada em um (falso positivo). Nos 37 pacientes com Tg baixa (< 10ng/cc) apenas um apresentou recidiva (verdadeiro negativo: 36 e falso negativo: 1). A análise estatística da capacidade da Tg em detectar recidivas mostrou: sensibilidade 85 por cento; especificidade 94 por cento; valor preditivo positivo 85 por cento; valor preditivo negativo 84 por cento e acurácia 95 por cento. CONCLUSÕES: Os resultados obtidos neste trabalho mostraram que a dosagem da Tg é de valor na detecção de possibilidade de recidivas no seguimento de pacientes operados por carcinoma diferenciado mesmo quando submetidos à cirurgia parcial.

BACKGROUND: Serum thyroglobulin determination has been reported to be a sensitive indicator of recurrent differentiated thyroid carcinoma. The purpose of this study is to determine the accuracy of serum thyroglobulin levels in predicting tumor recurrency after parcial thyroidectomy. METHODS: Forty eight patients with differentiated thyroid carcinoma were followed with serum thyroglobulin measurement after parcial thyroidectomy. Patiens recived hormonal suppressive therapy to maintain plasma TSH level below 0,6 mU/cc. Mean follow-up was 8,1 years. Serum thyroglobulin level above 10ng/cc was considered suspect of tumor recurrency. RESULTS: Eleven patients showed serum thyroglobulin level above 10 ng/cc. In four of them, elevations were considered spurious (hiparthyroidisme - 2 cases, and Hashimoto disease - 2 cases) and were excluded from statistical analysis. In the other 7, tumor recurrence was demonstrated in 6 (true positive: 6; false positive: 1). In 37 patients with low thyroglobulin level, only 1 had recurrence (true negative: 36; false negative: 1). Statistical analysis show sensibility 85 percent, specificity 94 percent, positive predictive value 85 percent, negative predictive value 84 percent and accuracy 95 percent. CONCLUSIONS: Serum thyroglobulin determination is an useful test to identify patients with persistent or recurrent differenctiated cancer, inicially submited to parcial thyroidectomy.

Carcinoma diferenciado da tireóide na infância / Childhood differentiated thyroid carcinoma

Os autores apresentam uma revisão de 12 casos de carcinoma da glândula tireóide em crianças, tratados na Seção de Cirurgia de Cabeça e Pescoço do Hospital do Câncer (INCa), no período entre 1986 e 1994. Trata-se de doença pouco freqüente, pois, neste levantamento, representou apenas 1,6% das 729 afecções cirúrgicas da tireóide e 10% dos 126 casos de carcinoma papilífero da glândula tireóide atendidos no período referido. A avaliação do sexo, forma de apresentação da doença, extensão do tumor inicial e resposta ao tratamento e evolução demonstraram que estas neoplasias acometem mais freqüentemente as meninas do que os meninos e, embora apresentem-se como forma de doença avançada desde a matrícula, geralmente respondem muito bem ao tratamento cirúrgico agressivo, o que proporciona, na maioria dos casos, um prognóstico bastante favorável.

The authors present a retrospective study of 12 childhood thyroid cancer seen at Hospital do Câncer (Rio de Janeiro - Brazil) from 1986 to 1994. The patient's age varied from seven to 13 years (median = 11 years), and all but one were female. Eleven children had papillary carcinoma and one follicular carcinoma. Seventy-five percent (nine patients) had cervical metastasis in presentation, and three presented pulmonary metastasis in any time of treatment. The tumor size ranged from 0,7 to six centimeters (median = 3 cm), 50%5 had capsular invasion all of them with cervical metastasis, tracheal invasion was detected in one patient, and the laryngeal recurrent nerve was partially compromised in two cases and had been functionally preserved in both. Only four patients were treated with less than total thyroidectomy but three of them had a second surgical procedure to complete thyroid resection since they developed cervical and/or distant metastasis. Radioactive iodine was used in eight patients with pulmonary metastasis or incomplete tumor resection. After a median follow-up period of four years all children are alive and with no evidence of disease. This is an infrequent children disease, and had represented only 1,6% of all surgical thyroid pathologies and 10% of thyroid papillary carcinoma treated in that period, and although tumor may be very aggressive in presentation, therapeutic result run with a long term prognostic when faced as a high risk disease.