title: A genetic and molecular update on adrenocortical causes of Cushing syndrome.
abstract: Primary adrenal Cushing syndrome is the result of cortisol hypersecretion mainly by adenomas and, rarely, by bilateral micronodular or macronodular adrenocortical hyperplasia. cAMP-dependent protein kinase A (PKA) signalling is the major activator of cortisol secretion in the adrenal cortex. Many adenomas and hyperplasias associated with primary hypercortisolism carry somatic or germline mutations in genes that encode constituents of the cAMP-PKA pathway. In this Review, we discuss Cushing syndrome and its linkage to dysregulated cAMP-PKA signalling, with a focus on genetic findings in the past few years. In addition, we discuss the presence of germline inactivating mutations in ARMC5 in patients with primary bilateral macronodular adrenocortical hyperplasia. This finding has implications for genetic counselling of affected patients; hitherto, most patients with this form of adrenal hyperplasia and Cushing syndrome were thought to have a sporadic and not a familial disorder.
authors.affiliation: Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Lodish
authors.affiliation: Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health Clinical Research Center, 31 Center Drive, Building 31, Room 2A46, MSC2425, Bethesda, Maryland 20892 USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000302:Adrenal Cortex / Q000503:physiopathology*; D000312:Adrenal Hyperplasia, Congenital; D000818:Animals; D003480:Cushing Syndrome / Q000235:genetics* / Q000503:physiopathology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases