Epidemiology, Clinical Presentation, and Diagnosis of Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from thyroid C cells that produces mainly calcitonin (Ctn) and is used as a tumor marker. MTC can occur either sporadically (75%) or in a hereditary variant (multiple endocrine neoplasia type 2, MEN2) due to germline mutations in the RET proto-oncogene. The discovery of MTC in a patient has several diagnostic implications involving a specific strategy, preoperative evaluation of the tumor marker Ctn and the extent of the disease, classification of MTC as sporadic or hereditary using germline RET testing, screening for associated endocrinopathies in hereditary MTC, and somatic RET testing in sporadic MTC. Elevated Ctn is a highly sensitive and specific tumor marker for the diagnosis and follow-up of MTC. Ctn is directly related to the tumor mass. In patients with nodular thyroid disease, MTC can be diagnosed by Ctn determination. Ctn is an indicator of tumor burden. Patients with confirmed sporadic or hereditary MTC should undergo total thyroidectomy. Depending on the preoperative Ctn value, additional dissection of the lymph nodes in the central and lateral neck compartments should be performed. In MEN 2 patients diagnosed by RET mutation analysis, the timing of prophylactic thyroidectomy depends on the specific RET mutation and Ctn level.