Nieman Lynnette K
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Endocr Rev. 2022 Sep 26;43(5):852-877. doi: 10.1210/endrev/bnab046.
Endogenous Cushing's syndrome (CS) is associated with morbidities (diabetes, hypertension, clotting disorders) and shortens life because of infections, pulmonary thromboembolism, and cardiovascular disease. Its clinical presentation is immensely variable, and diagnosis and treatment are often delayed. Thus, there are many opportunities for basic and clinical research leading to better tests, faster diagnosis, and optimized medical treatments. This review focuses on CS caused by excessive adrenocorticotropin (ACTH) production. It describes current concepts of the regulation of ACTH synthesis and secretion by normal corticotropes and mechanisms by which dysregulation occurs in corticotrope (termed "Cushing's disease") and noncorticotrope (so-called ectopic) ACTH-producing tumors. ACTH causes adrenal gland synthesis and pulsatile release of cortisol; the excess ACTH in these forms of CS leads to the hypercortisolism of endogenous CS. Again, the differences between healthy individuals and those with CS are highlighted. The clinical presentations and their use in the interpretation of CS screening tests are described. The tests used for screening and differential diagnosis of CS are presented, along with their relationship to cortisol dynamics, pathophysiology, and negative glucocorticoid feedback regulation in the two forms of ACTH-dependent CS. Finally, several gaps in current understanding are highlighted in the hope of stimulating additional research into this challenging disorder.
内源性库欣综合征（CS）与多种疾病（糖尿病、高血压、凝血障碍）相关，且由于感染、肺血栓栓塞和心血管疾病而缩短寿命。其临床表现变化极大，诊断和治疗常常延迟。因此，开展基础和临床研究以获得更好的检测方法、更快的诊断和优化的医学治疗有很多机会。本综述聚焦于由促肾上腺皮质激素（ACTH）分泌过多引起的CS。它描述了正常促肾上腺皮质激素细胞合成和分泌ACTH的调节的当前概念，以及在促肾上腺皮质激素细胞瘤（称为“库欣病”）和非促肾上腺皮质激素细胞瘤（所谓的异位）产生ACTH的肿瘤中发生调节异常的机制。ACTH导致肾上腺合成并脉冲式释放皮质醇；这些形式的CS中过量的ACTH导致内源性CS的皮质醇增多症。再次强调了健康个体与CS患者之间的差异。描述了临床表现及其在CS筛查试验解释中的应用。介绍了用于CS筛查和鉴别诊断的试验，以及它们与两种依赖ACTH的CS中皮质醇动态、病理生理学和负性糖皮质激素反馈调节的关系。最后，强调了当前认识中的几个空白，希望能激发对这一具有挑战性的疾病的更多研究。
