Molecular Derangements and the Diagnosis of ACTH-Dependent Cushing's Syndrome.

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Lynnette K Nieman
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Abstract

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.

促肾上腺皮质激素依赖性库欣综合征的分子病变与诊断。
内源性库欣综合征(CS)与多种疾病(糖尿病、高血压、凝血功能障碍)相关,并因感染、肺血栓栓塞和心血管疾病而缩短生命。其临床表现千变万化,诊断和治疗往往被延误。因此,基础和临床研究仍有很多机会,以获得更好的测试、更快的诊断和更优化的治疗。本综述重点讨论促肾上腺皮质激素(ACTH)分泌过多引起的 CS。它描述了正常促肾上腺皮质激素合成和分泌调节的现有概念,以及促肾上腺皮质激素分泌失调(称为 "库欣病")和非促肾上腺皮质激素分泌失调(所谓异位)的机制。促肾上腺皮质激素(ACTH)会导致肾上腺合成并脉冲式释放皮质醇;这些形式的 CS 中过量的促肾上腺皮质激素(ACTH)会导致内源性 CS 的皮质醇过多症。再次强调健康人与 CS 患者之间的差异。介绍了临床表现及其在 CS 筛查测试中的应用。介绍了用于 CS 筛查和鉴别诊断的测试,以及它们与皮质醇动态、病理生理学和两种形式的 ACTH 依赖性 CS 中糖皮质激素负反馈调节的关系。最后,强调了目前认识上的一些不足,希望能促进对这一具有挑战性的疾病的更多研究。
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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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