GENETIC TESTING AND EARLY THYROIDECTOMY FOR INHERITED MEDULLARY-THYROID CARCINOMA

The recent identification of mutations in the RET proto-oncogene that are associated with the multiple endocrine neoplasia type 2 (MEN 2) sy ndromes has allowed therapeutic intervention in affected individuals o n the basis of direct genetic testing. The principal endocrine neoplas m that occurs in patients with the MEN 2 syndromes is medullary thyroi d carcinoma. This thyroid neoplasm is the only consistently malignant feature of the MEN 2 syndromes and it is the most common cause of deat h in affected patients. Kindred members at risk for one of the MEN 2 s yndromes can be studied by direct DNA analysis to determine whether th ey have inherited a RET mutation. Those with a positive test can be tr eated by early thyroidectomy and cured when the disease is microscopic and localized to the thyroid gland. Total thyroidectomy is performed as early as at 5 years of age and is associated with minimal morbidity and virtually no mortality. Residual or persistent medullary thyroid carcinoma following thyroidectomy can best be determined by detecting increased levels of calcitonin following the administration of intrave nous calcium gluconate and pentagastrin.