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.