Multiple endocrine neoplasia type 2: Management of patients and subjects at risk

Multiple endocrine neoplasia type 2 (MEN-2) is an inherited multiglandular disease with age-related penetrance and variable expression. The prognosis of MEN-2 is linked to the carcinological evolution of medullary thyroid cancer (MTC), which depends mainly on the stage of discovery, and to the incidents related to pheochromocytomas. This emphasizes the need for early diagnosis and management of MEN-2. Since 1993, mutations evidenced on the protooncogene RET have allowed subjects at risk to be identified, thus leading to a three-step management of these patients. (I) For all the potentially affected members of a MEN-2 family, screening by molecular genetics of the ret gene enables one to identify the subjects at risk who bear the mutation. When no mutation is observed, a linkage analysis study may be proposed. (2) In the subjects at risk, early screening for the various types of endocrine lesions may then start in childhood and be performed using specific biological markers of MTC, pheochromocytoma and primary hyperparathyroidism, and particularly, basal and pentagastrin-stimulated calcitonin measurement, which is known to be the most sensitive marker for the monitoring of MTC. (3) This step of biological investigations enables the earliest possible treatment of any endocrine lesion detected before it is expressed clinically, thus improving the prognosis of MEN-2. When genetic screening cannot be performed, only annual clinical and biological monitoring remain available in all members of a family affected with MEN-2.