Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università "Federico II" di Napoli, Naples, Italy.
Unesco Chair for Health Education and Sustainable Development, University "Federico II", Naples, Italy.
Pituitary. 2022 Oct;25(5):726-732. doi: 10.1007/s11102-022-01262-8. Epub 2022 Aug 29.
Cushing's disease (CD), caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor, is the most common form of Cushing's syndrome (CS), accounting for approximately 70% of cases. CD requires a prompt diagnosis, an adequate treatment selection, and long-term management to limit hypercortisolism duration and long-term complications and improve patient outcomes. Pituitary surgery is the first-line option, which is non-curative in one third of patients, therefore requiring additional treatments. Medical therapy has recently acquired an emerging role, with the availability of several drugs with different therapeutic targets, efficacy and safety profiles. The current review focuses on efficacy and safety of steroidogenesis inhibitors, and particularly the historical drugs, ketoconazole and metyrapone, and the novel drugs levoketoconazole and osilodrostat, which seem to offer a rapid, sustained, and effective disease control. Ketoconazole should be preferred in females and in patients without severe liver disease; levoketoconazole may offer an alternative to classical ketoconazole, appearing characterized by a higher potency and potential lower hepatotoxicity compared to ketoconazole. Metyrapone should be preferred in males and in patients without severe or uncontrolled hypokalemia. Both ketoconazole and metyrapone may be preferred for short-term more than for long-term treatment. Osilodrostat may represent the best choice for long-term treatment, in patients with poor compliance to the multiple daily administration schedule, and in patients without severe or uncontrolled hypokalemia. Steroidogenesis inhibitors may be used alone or in combination, and associated with pituitary directed drugs, to improve the efficacy of the single drugs, allowing a potential use of lower doses for each drug, and hypothetically reducing the rate of adverse events associated with the single drugs. Clinicians may tailor medical therapy on the specific clinical scenario, considering disease history together with patients' characteristics and hypercortisolism's degree, addressing the needs of each patient in order to improve the therapeutic outcome and to reduce the burden of illness, particularly in patients with persistent or recurrent CD.
库欣病（Cushing's disease，CD）是由促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）分泌的垂体瘤引起的，是库欣综合征（Cushing's syndrome，CS）最常见的形式，约占病例的 70%。CD 需要及时诊断、适当的治疗选择和长期管理，以限制皮质醇过度分泌的持续时间和长期并发症，并改善患者的预后。垂体手术是首选治疗方法，但三分之一的患者无法治愈，因此需要额外的治疗。近年来，随着具有不同治疗靶点、疗效和安全性特征的多种药物的出现，药物治疗已逐渐发挥重要作用。目前的综述重点介绍了类固醇生成抑制剂的疗效和安全性，特别是历史药物酮康唑和米托坦，以及新型药物左酮康唑和奥昔罗司他，这些药物似乎能够快速、持续和有效地控制疾病。酮康唑应优先用于女性和无严重肝病史的患者；与酮康唑相比，左酮康唑可能提供一种替代方案，具有更高的效力和潜在的更低肝毒性。米托坦应优先用于男性和无严重或未经控制的低钾血症的患者。酮康唑和米托坦都可能更适合短期治疗而非长期治疗。奥昔罗司他可能是长期治疗的最佳选择，适用于对每日多次给药方案依从性差的患者，以及无严重或未经控制的低钾血症的患者。类固醇生成抑制剂可单独或联合使用，并与针对垂体的药物联合使用，以提高单药的疗效，使每种药物的剂量可能降低，并推测降低与单药相关的不良事件的发生率。临床医生可根据具体的临床情况制定药物治疗方案，综合考虑疾病史、患者特征和皮质醇过度分泌的程度，满足每位患者的需求，以改善治疗效果并减轻疾病负担，特别是在持续性或复发性 CD 患者中。
