Medullary carcinoma of the thyroid gland

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that has att racted a great deal of interest because of its frequent presentation as a f amilial tumor and its primary involvement in the type II multiple endocrine neoplasia (MEN) syndromes MEN-IIA and MEN-IIB and familial medullary thyro id carcinoma (FMTC). The MTC tumor cells secrete the polypeptide hormone ca lcitonin, which serves as an excellent tumor marker, useful for defining th e presence of disease, preoperatively or following thyroidectomy. The disco very that mutations in the RET proto-oncogene are associated with MEN-II sy ndromes was highly significant in that it demonstrated a clear correlation between genotype and phenotype; and most importantly it provided a mechanis m whereby family members at risk could be identified by direct DNA analysis . Virtually all patients with MEN-IIA, MEN-IIB, and FMTC develop MTC; there fore there is a clear rationale for performing thyroidectomy as soon as a R ET mutation has been identified. Because MTC appears to be much more aggres sive in patients with MEN-IIB, thyroidectomy is performed during the first year of life in this setting, whereas in patients with MEN-IIA, where the t umor appears to be more indolent, the procedure can be safety delayed until age 5 years. Reoperative neck exploration in patients with evidence of per sistent or recurrent MTC has been effective in a significant number of pati ents, although the success of the operation requires careful patient select ion and preoperative assessment. MTC, as expressed in the MEN-II syndromes, is an excellent model to evaluate the usefulness of interventional therapy in patients demonstrated to have a genetic predisposition for cancer.