Fleseriu Maria, Auchus Richard J, Bancos Irina, Biller Beverly M K
Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
J Endocr Soc. 2025 Feb 14;9(4):bvaf027. doi: 10.1210/jendso/bvaf027. eCollection 2025 Mar 3.
Although most cases of endogenous Cushing syndrome are caused by a pituitary adenoma (Cushing disease), approximately one-third of patients present with ectopic or adrenal causes. Surgery is the first-line treatment for most patients with Cushing syndrome; however, medical therapy is an important management option for those who are not eligible for, refuse, or do not respond to surgery. Clinical experience demonstrating that osilodrostat, an oral 11β-hydroxylase inhibitor, is effective and well tolerated comes predominantly from phase III trials in patients with Cushing disease. Nonetheless, reports of its use in patients with ectopic or adrenal Cushing syndrome are increasing. These data highlight the importance of selecting the most appropriate starting dose and titration frequency while monitoring for adverse events, including those related to hypocortisolism and prolongation of the QT interval, to optimize treatment outcomes. Here we use illustrative case studies to discuss practical considerations for the management of patients with ectopic or adrenal Cushing syndrome and review published data on the use of osilodrostat in these patients. The case studies show that to achieve the goal of reducing cortisol levels in all etiologies of Cushing syndrome, management should be individualized according to each patient's disease severity, comorbidities, performance status, and response to treatment. This approach to osilodrostat treatment maximizes the benefits of effective cortisol control, leads to improvements in comorbid conditions, and may ameliorate quality of life for patients across all types and severities of Cushing syndrome.
虽然大多数内源性库欣综合征病例是由垂体腺瘤（库欣病）引起的，但约三分之一的患者表现为异位或肾上腺病因。手术是大多数库欣综合征患者的一线治疗方法；然而，对于那些不适合手术、拒绝手术或对手术无反应的患者，药物治疗是一种重要的管理选择。表明口服11β-羟化酶抑制剂奥西卓司他有效且耐受性良好的临床经验主要来自于库欣病患者的III期试验。尽管如此，其在异位或肾上腺库欣综合征患者中使用的报道正在增加。这些数据凸显了在监测不良事件（包括与皮质醇减退和QT间期延长相关的不良事件）时选择最合适的起始剂量和滴定频率以优化治疗效果的重要性。在此，我们通过实例病例研究来讨论异位或肾上腺库欣综合征患者管理的实际注意事项，并回顾已发表的关于奥西卓司他在这些患者中使用的数据。病例研究表明，为实现降低所有病因的库欣综合征患者皮质醇水平的目标，管理应根据每位患者的疾病严重程度、合并症、体能状态和对治疗的反应进行个体化。这种奥西卓司他治疗方法可最大限度地发挥有效控制皮质醇的益处，改善合并症，并可能改善所有类型和严重程度的库欣综合征患者的生活质量。
