title: Multiple endocrine neoplasia, the old and the new: a mini review.
abstract: Multiple endocrine neoplasia syndromes have since been classified as types 1 and 2, each with specific phenotypic patterns. MEN1 is usually associated with pituitary, parathyroid and paraneoplastic neuroendocrine tumours. The hallmark of MEN2 is a very high lifetime risk of developing medullary thyroid carcinoma (MTC) more than 95% in untreated patients. Three clinical subtypesdMEN2A, MEN2B, and familial MTC (FMTC) have been defined based on the risk of pheochromocytoma, hyperparathyroidism, and the presence or absence of characteristic physical features). MEN2 occurs as a result of germline activating missense mutations of the RET (REarranged during Transfection) proto-oncogene. MEN2-associated mutations are almost always located in exons 10, 11, or 13 through 16. Strong genotype-phenotype correlations exist with respect to clinical subtype, age at onset, and aggressiveness of MTC in MEN2. These are used to determine the age at which prophylactic thyroidectomy should occur and whether screening for pheochromocytoma or hyperparathyroidism is necessary. Specific RET mutations can also impact management in patients presenting with apparently sporadic MTC. Therefore, genetic testing should be performed before surgical intervention in all patients diagnosed with MTC. Recently, Pellegata et al. have reported that germline mutations in CDKN1B can predispose to the development of multiple endocrine tumours in both rats and humans and this new MEN syndrome is named MENX and MEN4, respectively. CDKN1B. A recent report showed that in sporadic MTC, CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker. New insights on MEN syndrome pathogenesis and related inherited endocrine disorders are of particular interest for an adequate surgical and therapeutic approach.
authors.affiliation: Second University of Napoli, Napoli, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pasquali
authors.forename: F M
authors.initials: FM
authors.lastname: Di Matteo
authors.forename: A
authors.initials: A
authors.lastname: Renzullo
authors.forename: G
authors.initials: G
authors.lastname: Accardo
authors.forename: D
authors.initials: D
authors.lastname: Esposito
authors.forename: F
authors.initials: F
authors.lastname: Barbato
authors.forename: V
authors.initials: V
authors.lastname: Colantuoni
authors.forename: L
authors.initials: L
authors.lastname: Circelli
authors.forename: G
authors.initials: G
authors.lastname: Conzo
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000483:Alleles; D000818:Animals; D015415:Biomarkers / Q000097:blood; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D018450:Disease Progression; D005091:Exons; D005838:Genotype; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics; D009377:Multiple Endocrine Neoplasia / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics; D020125:Mutation, Missense; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D018570:Risk Assessment; D012307:Risk Factors; D013577:Syndrome; D013964:Thyroid Neoplasms / Q000235:genetics; D013965:Thyroidectomy; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D050760:Cyclin-Dependent Kinase Inhibitor p27