[Multiple endocrine neoplasia type 2]

Multiple endocrine neoplasia type 2 syndrome (MEN-2) is a rare hereditary cancer syndrome with autosomal dominant trait of inheritance. The most characteristic feature of this syndrome is a complete penetrance of medullary thyroid cancer. On the basis of differences in variable expression of pheochromocytomas, hyperparathyroidism, and other clinical features, MEN-2 is divided into three clinical variants, referred to as MEN-2A, MEN-2B and familial medullary thyroid cancer. In the most frequent variant, MEN-2A syndrome, apart from thyroid carcinoma, this syndrome includes also unilateral or bilateral pheochromocytoma and hyperparathyroidism. In less common MEN-2B, medullary thyroid cancer and pheochromocytoma occur together with complex nervous and skeletal abnormalities. Familial medullary thyroid cancer is a variant of MEN-2 in which individuals affected develop only this neoplasm without other manifestations of MEN-2. It is well known that MEN-2 is caused by mutations of different codons of the RET proto-oncogene. The identification of mutations associated with this syndrome has led to genetic testing to identify patients at risk for MEN-2. There is a significant genotype-phenotype correlation, which allows a more individualised approach to the timing of prophylactic thyroidectomy. In this paper, we review the current views on the etiopathogenesis, clinical presentation, diagnosis and treatment of MEN-2.