Multiple endocrine neoplasia type 2

Curr Treat Options Oncol. 2004 Aug;5(4):315-25. doi: 10.1007/s11864-004-0022-6.


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.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adrenal Gland Neoplasms / mortality
  • Adrenal Gland Neoplasms / pathology
  • Adrenal Gland Neoplasms / therapy*
  • Adrenalectomy / methods
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Carcinoma, Medullary / mortality
  • Carcinoma, Medullary / pathology
  • Carcinoma, Medullary / therapy*
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Multiple Endocrine Neoplasia Type 2a / mortality
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Multiple Endocrine Neoplasia Type 2a / therapy*
  • Neoplasm Staging
  • Pheochromocytoma / mortality
  • Pheochromocytoma / pathology
  • Pheochromocytoma / therapy*
  • Proto-Oncogene Mas
  • Risk Assessment
  • Survival Analysis
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / therapy*
  • Thyroidectomy / methods
  • Treatment Outcome