However, there is a variable biological activity of the MTC depending on the clinical setting. The thyroid carcinoma is very aggressive in patients with MEN 2B, developing at an early age and rapidly metastasizing to regional and distant sites. By contrast, the MTC that occurs in FMTC develops late in life and grows slowly. In patients with MEN 2A, the MTC has a variable clinical behavior usually progressing in an indolent fashion, but it may grow rapidly in occasional cases. The MEN 2 syndromes are inherited in a dominant fashion, with near complete penetrance.
Genetic counseling is recommended for high-risk families considering genetic testing.
Counseling includes a review of the risks, benefits, and limitations of genetic testing as well as a personalized assessment of the probability of being a mutation carrier. The discovery that mutations in the RET protooncogene are responsible for the MEN 2 syndromes provides an opportunity for a unique therapeutic intervention. Since MTC is the most common cause of death in patients with these syndromes, prophylactic thyroidectomy is recommended based on direct DNA testing of patients at risk for inheriting the genetic mutation. In children with MEN 2A or FMTC, surgery should be performed at about 5 years of age. Because of the increased aggressiveness of MTC in MEN 2B patients, the thyroid gland should be removed at about one year.