Medullary thyroid cancers (MTC) are rare tumors of neuroendocrine origin that arise from parafollicular C cells which secrete calcitonin and other peptides and hormones.  Sporadic MTC accounts for 75% of cases, and inherited MTC constitutes the rest.  Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occur.  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant syndrome, characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, in one variant, primary hyperparathyroidism (PHPT).

MEN2 can be classified into three forms: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC).  Familial medullary thyroid carcinoma (FMTC) accounts for 10-20% of all MEN2 cases.  The diagnosis of MTC is based on history, physical exam, calcitonin and CEA levels, imaging, and fine needle aspiration biopsy.  Every patient with MTC should undergo DNA analysis for the presence of the RET mutation.  FMTC is diagnosed in families with four cases of medullary thyroid carcinoma (MTC) in the absence of pheochromocytoma or parathyroid adenoma.  MTC typically occurs in middle age in FMTC and may be subclinical.

The best treatment for FMTC is surgery.  A prophylactic thyroidectomy is recommended for all patients with an identified RET mutation between the ages of 2-5.  Also, lifelong thyroid hormone supplementation is needed.  The prognosis of MTC depends on the stage at which it is diagnosed and quality of initial surgical treatment.

Mutations in the RET (Ret proto-oncogene), at the chromosomal region 10q11.2, account for the clinical subtypes of MEN2. About 95% of individuals with FMTC are identifiable through RET testing. FMTC cases has also been reported with mutations in NTRK1 (Neurotrophic Receptor Tyrosine Kinase 1) gene.