Cirugía profiláctica en cáncer medular de tiroides hereditario / Prophylactic surgery in hereditary medullary thyroid cancer

Introducción: Se estima que del total de los cánceres, el 5-10% tendría una base genética. Actualmente es posible identificar a los individuos con predisposición genética en algunos cánceres como manera de intervenir precozmente en el desarrollo de esta enfermedad. Objetivos: Evaluar la utilidad de la cirugía profiláctica en el cáncer medular de tiroides hereditario. Material y métodos: Este trabajo es una revisión de literatura de diferentes estudios extraídos de bibliotecas electrónicas como Scientific Electronic Library Online (SciELO), MedLine-PubMed y UpToDate, mediante la construcción de preguntas clínicas y términos MeSH enfocados principalmente en la búsqueda específica de información sobre el cáncer medular de tiroides hereditario. Resultados: Los estudios revisados demuestran que la tiroidectomía profiláctica con resección linfática cervical representa el único tratamiento eficaz en el caso del cáncer medular de tiroides hereditario. Conclusiones: La cirugía profiláctica ha demostrado una importante disminución del riesgo de cáncer de tiroides y se considera una conducta de rigor en portadores del gen RET en el cáncer medular de tiroides.

Introduction: Approximately 5-10% of global cancer has a genetic base. Nowadays it is possible to identify those who have a genetic predisposition for some cancers, so they can be treated in short term. Objectives: Evaluate how useful is prophylactic surgery on hereditary Medullary Thyroid Cancer. Materials and methods: This investigation is a literature review of different research papers from electronic databases such as Scientific Electronic Library Online (SciELO), MedLine-PubMed and UpToDate. The research was made with clinical queries and MeSH terms, specially focused on hereditary Medullary Thyroid Cancer. Results: This research shows that prophylactic Thyroidectomy with cervical lymph node resection is the only effective and curative treatment for hereditary Medullary Thyroid Cancer. Conclusions: Prophylactic surgery has proof an important role decreasing the risk on Hereditary Thyroid cancer Syndrome and in RET carriers surgery is considered a must.

Multiple endocrine neoplasia: the Chilean experience

Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called "3 P's": parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia.

Valor diagnóstico da tomografia por emissão de pósitrons / tomografia computadorizada (PET-CT) com flúor-18 fluordeoxiglicose (FDG-18F) em pacientes com carcinoma diferenciado da tireóide, níveis séricos de tireoglobulina elevados e pesquisa de corpo inteiro com iodo negativa / Diagnostic value of positron emission tomography / computed tomography with fluorine-18 fluordeoxyglucose in patients with differentiated thyroid gland carcinoma, high thyroglobulin serum levels and negative iodine whole body scan

OBJETIVO: Avaliar o papel da PET-CT com FDG-18F na detecção de recidiva e/ou metástase de carcinoma diferenciado da tireóide (CDT) em pacientes com níveis elevados de tireoglobulina (TG) e PCI negativa. PACIENTES E MÉTODO: Os achados da PET-CT de 25 pacientes foram comparados com a avaliação histopatológica e os métodos convencionais de imagem (MC). RESULTADOS: A PET-CT foi positiva em 16 pacientes com resultado verdadeiro-positivo em 14 e falso-positivo em 2 casos (valor preditivo positivo 87,5 por cento). Nove pacientes tiveram PET-CT negativa; dois evoluíram com níveis indetectáveis de TG. Doença residual foi observada na PCI pós-dose terapêutica de uma paciente. Seis pacientes não apresentaram evidências de tumor durante o seguimento (média 16 meses). PET-CT foi concordante com MC em 52 por cento, parcialmente concordante em 12 por cento e discordante (6 falso-negativos e 3 falso-positivos dos MC) em 36 por cento. Foi observada uma tendência de aumento da proporção de PET-CT positiva com o aumento de TG. CONCLUSÃO: A PET-CT com FDG-18F é útil na detecção de recidiva e/ou metástases de CDT com níveis de TG elevados mas PCI negativa. Apresenta alto valor preditivo positivo e é superior aos MC, sendo mais efetiva quanto maior o nível de TG.

PURPOSE: To evaluate the role of PET-CT with FDG-18F in the detection of recurrence and/or metastasis of differentiated thyroid carcinoma (DTC) in patients with elevated levels of thyroglobulin (TG) and negative whole body scan (WBS). PATIENTS AND METHOD: PET-CT findings of 25 patients were compared to histopathology evaluation and conventional imaging (CI). RESULTS: PET-CT scan was positive in 16 patients finding 14 true-positive and 2 false-positive cases (positive predictive value 87.5 percent). Nine patients had negative PET-CT; two had decrease of TG to undetectable levels. One patient had residual disease detected by post-therapeutic WBS. Six patients had no evidence of tumor during follow-up (mean time 16 months). PET-CT was concordant with CI in 52 percent, partially concordant in 12 percent and discordant in 36 percent (6 false-negatives and 3 false-positive of CI). We observed a tendency of increasing proportion of positive PET-CT with increasing TG. CONCLUSION: PET-CT scan with FDG-18F is useful in the detection of recurrence and/or metastases of DTC with high TG levels but negative WBS. It presents elevated positive predictive value and is superior to CI being more effective as higher the serum TG levels.

Impacto do rastreamento do gene RET na abordagem de uma família com neoplasia endócrina múltipla tipo IIA / The impact of RET gene mutations screening in the management of a family with multiple endocrine neoplasia type IIA

Introdução: a neoplasia endócrina múltipla tipo IIA (NEM IIA) é uma doença familial com padrão de herança autossômico dominante, expressão clínica variável e se caracteriza pela presença do carcinoma medular da tireóide, feocromocitoma e hiperparatireoidismo. Há 12 anos, mutações no gene RET foram identificadas como responsáveis pela NEM IIA. Esse gene codifica um receptor de membrana da família das tirosina-quinases, associado à proliferação e diferenciação celulares, sendo expresso nas células derivadas do neuroectoderma (células C parafoliculares e da medula adrenal), bem como nas paratireóides. Objetivo: estudar uma família com NEM IIA (quatro gerações), através do caso índice que apresenta carcinoma medular da tireóide e hiperparatireoidismo. Método: foram analisados o heredograma e a expressão fenotípica de 20 membros da família, bem como o sequenciamento do gene RET (exon 11). Resultados: cinco indivíduos apresentavam carcinoma medular da tireóide, tendo um deles também hiperparatireoidismo (caso- índice). O feocromocitoma não identificado. O estudo molecular do gene RET em 17 indivíduos revelou a presença da mutação Cys634Tyr no códon 634 nos cinco indivíduos com carcinoma medular da tireóide e em cinco indivíduos sem este diagnóstico (portadores). Conclusões: o estudo clínico e molecular desta família permitiu a identificação dos indivíduos em risco de desenvolver carcinoma medular da tireóide, uma doença potencialmente letal, bem como a adequada orientação e aconselhamento genético desses pacientes.

Tiroidectomía profiláctica en niños y jóvenes con cáncer medular tiroideo hereditario: Experiencia chilena / Prophylactic thyroidectomy in children and young people with hereditary medullary thyroid carcinoma: A Chilean experience

Background: With the availability of the RET proto-oncogene genetic testing, it is possible to perform prophylactic total thyroidectomy among carriers of RET mutation. Aim: To evaluate the histological findings and the effects of the prophylactic total thyroidectomy in first-degree relatives of Chilean patients with multiple endocrine neoplasia type 2 (MEN 2) based on the Ret proto-oncogen analysis. Subjects and Methods: Nineteen patients belonging to 11 MEN 2 families underwent total thyroidectomy. Of these, 16 either with C cell hyperplasia (CCH) or microscopic medullary thyroid carcinoma (MTC) were selected for the final analysis. Results: The age at the moment of thyroidectomy ranged from 3 to 24 years (median 9.5). The most common mutation was located in codon 634 (69%) followed by codon 620 (25%). Histopathology revealed MTC in 13 patients (81%, youngest 3 years, oldest ones 19 and 24 years) and CCH in 3. A significant correlation was observed between basal preoperative serum calcitonin/tumor size (r= 0.53, P <0.05) and age/tumor size (r= 0.56, P <0.03), but not between basal preoperative serum calcitonin and age. Stimulated preoperative calcitonin levels were confounding and not useful for differentiating CCH from MTC. None of patients in whom cervical dissection was done (9/16) presented lymph node metastases, including the oldest ones. All patients but the older ones were biochemically cured after a mean of 5 years of follow-up. Conclusion: Prophylactic total thyroidectomy should be done early in life because there is an age-dependent progression from HCC to MTC. MTC often precedes biochemical detection of the disease.