Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Abstract

Introduction: Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. Objective: The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. Materials and methods: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Results: Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. Conclusions: MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies. Arq Bras Endocrinol Metab. 2014;58(7):667-700

Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives

“…The routine use of serum calcitonin in the evaluation of thyroid nodules is not a consensus. The European Thyroid Society recommends it, but not the Brazilian Society of Endocrinology (Schlumberger et al 2012, Maia et al 2014, while the current guidelines of the American Thyroid Association state that there is no evidence to recommend for or against calcitonin measurements in nodule evaluations (Haugen et al 2016). There was an agreement that, in certain situations, such as patients considered for less than total thyroidectomy or with suspicious cytology not consistent with papillary thyroid cancer, serum calcitonin measurement should be considered.…”

“…Surgery is the only curative treatment for MTC. Total thyroidectomy with central lymph node dissection is the procedure of choice and, depending on the serum calcitonin levels, and preoperative cervical US imaging, a more extensive surgery with lateral neck dissection should be considered (Maia et al 2014, Wells et al 2015, Wells 2018. Patients with intrathyroidal tumor have a 10-year survival rate of 95.6%, whereas patients with regional stage disease or distant metastasis at diagnosis present overall survival rates of 75.5 and 40%, respectively (Roman et al 2006).…”

“…Distant metastases should be investigated if serum calcitonin levels are above 500 pg/mL preoperative or 150 pg/mL post-total thyroidectomy. Neck and/or chest CT, liver MRI, bone scintigraphy, and, eventually, [ 18 F]-fluorodeoxyglucose positron emission computed tomography ( 18 F-FDG PET/CT) or 18 F-dihydroxyphenylalanine ( 18 F-DOPA PET/CT) might be used (Maia et al 2014, Wells et al 2015. The 18 F-DOPA PET/CT appears to be particularly useful in detecting lesions in patients with recurrent MTC and negative imaging studies (Romero-Lluch et al 2017).…”

Biochemical Testing in Thyroid Disorders

“…CEA is a nonspecific tumor marker for medullary thyroid cancer, but it does help to predict outcome. 124–126 Owing to its prolonged half-life, serum levels of CEA may take even longer to reach a nadir. In addition, CEA level can be falsely elevated owing to heterophilic antibodies, smoking, gastrointestinal tract inflammatory disease, benign lung tumors, or several nonthyroid malignancies.…”

Effect of 3′UTR RET Variants on RET mRNA Secondary Structure and Disease Presentation in Medullary Thyroid Carcinoma

“…The RET (REarranged during Transfection) proto-oncogene is the susceptibility gene for hereditary MTC and RET molecular analysis is now considered critical in MTC management [ 4 , 5 ]. Genotype–phenotype correlation has been reported and mutations in exons 5, 8, 10, 11, 14, 15 or 16 occur in more than 98% of MEN2 families [ 4 , 5 ]. The RET gene, a member of the cadherin superfamily, encodes a receptor tyrosine kinases, which are cell-surface molecules that transduce signals for cell growth and differentiation.…”