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.

中文翻译：

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分子紊乱和 ACTH 依赖性库欣综合征的诊断。


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，并因感染、肺血栓栓塞和心血管疾病而缩短寿命。其临床表现变化很大，诊断和治疗常常被延误。因此，基础和临床研究有很多机会可以实现更好的测试、更快的诊断和优化的医疗。本综述重点关注促肾上腺皮质激素 (ACTH) 产生过多引起的 CS。它描述了正常促肾上腺皮质激素调节 ACTH 合成和分泌的当前概念，以及促肾上腺皮质激素（称为“库欣病”）和非促肾上腺皮质激素（所谓异位）产生 ACTH 的肿瘤中发生失调的机制。 ACTH 引起肾上腺合成和皮质醇的脉冲式释放；这些形式的 CS 中过量的 ACTH 会导致内源性 CS 的皮质醇增多症。健康个体与 CS 患者之间的差异再次凸显。描述了临床表现及其在解释 CS 筛查测试中的用途。介绍了用于筛查和鉴别诊断 CS 的测试，以及它们与两种形式的 ACTH 依赖性 CS 中皮质醇动力学、病理生理学和负糖皮质激素反馈调节的关系。最后，强调了当前理解中的一些差距，希望刺激对这种具有挑战性的疾病的更多研究。