Multiple endocrine neoplasia type 2B - genetic basis and clinical expression

Multiple endocrine neoplasia (MEN) type 2B is a heritable endocrine disorde r characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, mul tiple mucosal neuromas, and a marfanoid habitus. Intestinal ganglioneuromat osis, corneal nerve thickening and skeletal abnormalities are also often pr esent, The disease is inherited in an autosomal dominant fashion and is cau sed by a single mutation in the RET proto-oncogene, with a methionine to th reonine substitution at codon 918. The MTC in MEN 2B presents at an earlier age and tends to be more aggressive than the MTC in MEN 2A. It is multicen tric and bilateral and occurs as young as age 3, with early lymph node meta stases. Pheochromocytoma is also often bilateral but is rarely malignant. I f pheochromocytoma is detected, adrenalectomy should precede thyroidectomy to avoid intraoperative catecholamine crisis. Patients at risk For MEN 2B s hould undergo genetic screening in infancy. Total thyroidectomy should be p erformed on all patients positive for RET mutations even prior to the onset of clinical symptoms. (C) 2001 Published by Elsevier Science Ltd.