Multiple Endocrine Neoplasia Type 2A (including Familial Medullary Carcinoma) and Type 2B

Multiple Endocrine Neoplasia (MEN) type 2 A and B autosomal dominant syndromes are rare endocrinopathies characterized by tumors of the C cells of the thyroid, adrenal medulla and parathyroid glands.. MEN2A have either C-cell hyperplasia (CCH) or medullary thyroid cancer (MTC), 50% pheochromocytoma (Pheo), and 20-30% hyperparathyroidism (HPT). Patients with MEN2B have a 100% incidence of CCH or MTC, Pheo (30-50%), a Marfanoid habitus and mucosal neuromas, rarely HPT. About 25% of patients with MTC have one of these familial syndromes. FMTC is a variant of MEN2A. Up to 23% of Pheo patients also have either MEN2 or von-Hippel-Lindau disease. Familial forms of these tumors are multifocal, have hyperplasia as a precursor to frank tumors and different clinical behaviors. Ultrasound, FNA cytology of the thyroid combined with immunostains is recommended to make the diagnosis. The MEN2 RET proto-oncogene, on chromosome 10 (10q11-2), is a transmembrane tyrosine kinase with a long extracellular domain, a single transmembrane region, and two cytosplasmic tyrosine kinase domains. Patients with MEN-2B typically have a point mutation in the intracellular kinase catalytic domain. The most important biomarker is calcitonin and provocative testing for elevation of TCT in response to pentagastrin or calcium helpful but the diagnosis is made by genetic testing. Fractionated metanephrines are used for pheochromocytoma and PTH for hyperparathyroidism. Screening should be done early and cure can be achieved with total thyroidectomy for MTC and adrenalectomy for pheochromocytoma. Recurrent MTC requires history, physical examination, neck ultrasound, and measurement of serum calcitonin and carcinoembryonic antigen (CEA) levels every 6 months. F-DOPA PET/CT or conventional FDG PET/CT, are able to detect MTC metastases or disease progression. Treatment can be successful with a TKI such as Sunitinib, Vanetanib and Sorafenib. For complete coverage of this and related areas of Endocrinology, please visit our free online textbook, WWW.ENDOTEXT.ORG.