Multiple endocrine neoplasia type 2.
Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome that is transmitted in an autosomal dominant pattern. MEN-2A, MEN-2B, and familial medullary thyroid cancer (MTC) comprise the MEN-2 syndrome. A germline mutation in the RET proto-oncogene is responsible for the MEN-2 syndrome. Recent data indicate that in 99% of MEN-2 cases, a germline RET mutation can be identified by genetic testing. The phenotypic variation of MEN-2 is diverse and partly related to the codon and specific point mutation in the RET proto-oncogene. There are increasing data on the genotype-phenotype correlations in patients with MEN-2 and this information should be used for screening at-risk patients and treatment of RET mutation carriers. All patients (especially if young) with MTC or bilateral pheochromocytoma should have a careful family history taken and genetic screening for RET germline mutations. Patients who are RET germline mutation carriers but without clinical or biochemical evidence of MTC should have a prophylactic total thyroidectomy. The optimal age of thyroidectomy should be based on the RET genotype (eg, high-risk mutations within the first year of life, intermediate-risk mutations by 5 years of age, and low-risk mutations by 10 years of age). Patients who are diagnosed with clinical or biochemical evidence of MTC should have a total or a near total thyroidectomy and at least a central neck lymph node dissection. Patients who have pheochromocytoma and a unilateral adrenal tumor on a localizing study should have a unilateral laparoscopic adrenalectomy after preoperative alpha-blockade. However, patients with bilateral adrenal tumors on localizing studies should have bilateral laparoscopic adrenalectomy. A cortical-sparing (subtotal) adrenalectomy may be considered, if technically feasible, to avoid long-term steroid dependence and to reduce the risk of Addisonian crisis. Patients with biochemical evidence of primary hyperparathyroidism should have a bilateral neck exploration and total parathyroidectomy and autotransplantation (30-60 mg of the most normal parathyroid tissue) to the nondominant forearm if asymmetric parathyroid hyperplasia is present. Rarely, patients may have only single-gland disease and excision may be performed if the other parathyroid glands are not found with biopsy to be hyperplastic. All unresected parathyroid glands should be marked with a clip because patients with MEN-2A have a high risk of persistent and recurrent primary hyperparathyroidism. Patients with familial MTC may have not manifested the other features of MEN-2A, thus these patients should have continued follow-up for pheochromocytoma and primary hyperparathyroidism.
Gertner
Michael E
ME
Department of Surgery, University of California San Francisco, 1600 Divisadero Street, C3-47, San Francisco, CA 94115, USA.
Kebebew
Electron
E
D000310:Adrenal Gland Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000315:Adrenalectomy / Q000379:methods; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018276:Carcinoma, Medullary / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010673:Pheochromocytoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000090063:Proto-Oncogene Mas; D018570:Risk Assessment; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013965:Thyroidectomy / Q000379:methods; D016896:Treatment Outcome