title: MEN1, MEN4, and Carney Complex: Pathology and Molecular Genetics.
abstract: Pituitary adenomas are a common feature of a subset of endocrine neoplasia syndromes, which have otherwise highly variable disease manifestations. We provide here a review of the clinical features and human molecular genetics of multiple endocrine neoplasia (MEN) type 1 and 4 (MEN1 and MEN4, respectively) and Carney complex (CNC). MEN1, MEN4, and CNC are hereditary autosomal dominant syndromes that can present with pituitary adenomas. MEN1 is caused by inactivating mutations in the MEN1 gene, whose product menin is involved in multiple intracellular pathways contributing to transcriptional control and cell proliferation. MEN1 clinical features include primary hyperparathyroidism, pancreatic neuroendocrine tumours and prolactinomas as well as other pituitary adenomas. A subset of patients with pituitary adenomas and other MEN1 features have mutations in the CDKN1B gene; their disease has been called MEN4. Inactivating mutations in the type 1α regulatory subunit of protein kinase A (PKA; the PRKAR1A gene), that lead to dysregulation and activation of the PKA pathway, are the main genetic cause of CNC, which is clinically characterised by primary pigmented nodular adrenocortical disease, spotty skin pigmentation (lentigines), cardiac and other myxomas and acromegaly due to somatotropinomas or somatotrope hyperplasia.
authors.affiliation: Section on Endocrinology and Genetics, <italic>Eunice Kennedy Shriver</italic> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md., USA.
authors.forename: Marie Helene
authors.initials: MH
authors.lastname: Schernthaner-Reiter
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000172:Acromegaly / Q000235:genetics; D000818:Animals; D056733:Carney Complex / Q000235:genetics* / Q000473:pathology*; D004701:Endocrine Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D015175:Prolactinoma / Q000235:genetics / Q000473:pathology