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.
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.
Nat Rev Endocrinol. 2016 May;12(5):255-62. doi: 10.1038/nrendo.2016.24. Epub 2016 Mar 11.
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.
原发性肾上腺库欣综合征是由皮质醇过度分泌引起的，主要由腺瘤引起，很少由双侧微结节或大结节性肾上腺皮质增生引起。cAMP 依赖性蛋白激酶 A（PKA）信号通路是肾上腺皮质中皮质醇分泌的主要激活剂。许多与原发性皮质醇增多症相关的腺瘤和增生携带编码 cAMP-PKA 通路成分的基因的体细胞或种系突变。在这篇综述中，我们讨论了库欣综合征及其与失调的 cAMP-PKA 信号通路的联系，重点讨论了过去几年的遗传发现。此外，我们还讨论了原发性双侧大结节性肾上腺皮质增生患者中 ARMC5 种系失活突变的存在。这一发现对受影响患者的遗传咨询具有重要意义；迄今为止，大多数患有这种形式的肾上腺增生和库欣综合征的患者被认为是散发性疾病，而不是家族性疾病。
