Prophylactic thyroidectomy in multiple endocrine neoplasia type 2

Medullary thyroid carcinoma (MTC) is the main component of the autosomal dominant cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). MEN 2 is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. In RET-mutation carriers, an age-related progression has been documented from normal C-cells to premalignant C-cell hyperplasia and finally to MTC with or without cervical lymph node metastases. The time required for this neoplastic development as well as penetrance and aggressiveness of disease mainly depends on the specific RET mutation with a strong genotype-phenotype correlation. Recommendations for the timing of prophylactic thyroidectomy are based upon a model that utilizes these genotype-phenotype correlations to stratify mutations into four risk levels. The excellent prognosis for MTC diagnosed at its earliest stage underscores the importance of early diagnosis by RET-mutation analysis for hereditary MTC.