Management of patients with hereditary medullary thyroid carcinoma.

The heredity of medullary thyroid carcinoma within MEN2 syndrome is caused by heterozygous germline mutations in the RET proto-oncogene. Since MEN2-associated mutations involve only hot spots, the molecular genetic analysis of the RET proto-oncogene constitutes the perfect tool for the diagnosis of MEN2, being thus considered the standard method. The molecular genetic screening for MEN2-associated RET germline mutations should be carried out in all patients with an apparently sporadic medullary thyroid carcinoma or pheochromocytoma. This testing needs to include exons 10, 11, and 13 to 16 of the RET proto-oncogene. Such investigations are aimed at identifying an index person of a new MEN2 family. The detection of such a RET germline mutation is the basis for predictive molecular genetic testing within an affected family, and allows the exclusion or identification of gene carriers. For these family members at risk, prophylactic total thyroidectomy is recommended as a curative procedure, according to a risk-adapted, genetically based treatment algorithm. The management of such affected families should be always complemented by oncological and genetic counselling.