Tritos Nicholas A, Biller Beverly M K
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Discov Med. 2012 Feb;13(69):171-9.
Cushing's syndrome (CS) is a heterogeneous disorder of diverse etiologies, leading to cortisol excess. Endogenous CS is caused by tumors secreting adrenocorticotropin (ACTH) (either eutopically or ectopically), cortisol, or very rarely corticotropin-releasing hormone (CRH). Definitive therapy of endogenous CS optimally involves tumor resection. Indications for medical therapy include acutely ill patients in preparation for surgery, those for whom surgery is not indicated (such as patients with unknown tumor location or unresectable lesions, and patients unfit for surgery for medical reasons), or patients who remain hypercortisolemic postoperatively. In the current article, the published literature has been reviewed to summarize data on medical therapies used in CS. Several agents are either used "off label" or being studied as potential therapies for CS. Medications suppressing adrenal steroidogenesis currently in use include ketoconazole, metyrapone, mitotane, or etomidate. In addition, the investigational agent LCI699 is under study. Centrally acting agents, which suppress ACTH secretion, include cabergoline, octreotide, as well as the investigational agents pasireotide, bexarotene, and lapatinib, which are being studied in patients with pituitary tumors. Mifepristone, a type 2 glucocorticoid receptor antagonist, was recently approved by the FDA as a new therapy for CS. Although not definitive at present, medical therapies have an important role in the management of CS patients. It is anticipated that understanding the pathogenesis of these tumors at a molecular level may spawn the development of rationally designed, highly efficacious medical therapies for CS in the future.
库欣综合征（CS）是一种病因多样的异质性疾病，可导致皮质醇分泌过多。内源性CS由分泌促肾上腺皮质激素（ACTH）（无论是原位还是异位）、皮质醇或极罕见的促肾上腺皮质激素释放激素（CRH）的肿瘤引起。内源性CS的确定性治疗最佳方案是肿瘤切除。药物治疗的适应证包括为手术做准备的急性病患者、不适合手术的患者（如肿瘤位置不明或病变无法切除的患者，以及因医学原因不适合手术的患者），或术后仍存在高皮质醇血症的患者。在本文中，对已发表的文献进行了综述，以总结关于CS药物治疗的数据。几种药物要么是“超适应证”使用，要么正在作为CS的潜在治疗方法进行研究。目前使用的抑制肾上腺类固醇生成的药物包括酮康唑、美替拉酮、米托坦或依托咪酯。此外，研究药物LCI699正在进行研究。抑制ACTH分泌的中枢作用药物包括卡麦角林、奥曲肽，以及正在垂体肿瘤患者中进行研究的研究药物帕瑞肽、贝沙罗汀和拉帕替尼。米非司酮是一种2型糖皮质激素受体拮抗剂，最近被美国食品药品监督管理局（FDA）批准为CS的一种新治疗方法。虽然目前还不是确定性的，但药物治疗在CS患者的管理中具有重要作用。预计在分子水平上了解这些肿瘤的发病机制可能会在未来催生出合理设计的、高效的CS药物治疗方法。
