Aix Marseille University, Marseille Medical Genetics, INSERM U1251 and Assistance Publique Hopitaux de Marseille, La Conception Hospital, Department of Endocrinology, Marseille 13005, France.
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Clin Endocrinol Metab. 2021 Jun 16;106(7):2114-2123. doi: 10.1210/clinem/dgab122.
Steroidogenesis inhibitors can be given to control the hypercortisolism of Cushing's syndrome in various situations: when surgery has been unsuccessful or not possible; in metastatic adrenocorticotropin hormone (ACTH) or cortisol-secreting tumors; when waiting for the maximal efficacy of radiation techniques; for rapid treatment of severe hypercortisolism in patients with occult ACTH-producing tumors; or as a presurgical treatment in patients with severe comorbidities. Whilst biochemical "control" can be achieved in more than 50% of cases, daily management of such drugs can be challenging. Indeed, with a "dose-titration" or a "block and replace" approach, defining eucortisolism is usually difficult, requiring the measurement of several biological markers. Moreover, each drug has its own side effects, which must be monitored closely. The aim of this "approach to the patient" is to shed light on the management of hypercortisolism with 4 steroidogenesis inhibitors (ketoconazole, levoketoconazole, metyrapone, osilodrostat) to help endocrinologists dealing with patients with Cushing's syndrome. Various points will be discussed, such as initial dose of treatment, dose schedule, monitoring of efficacy, and side effects of monotherapy. The combination of steroidogenesis inhibitors will also be discussed.
手术不成功或无法进行时；在转移性促肾上腺皮质激素（ACTH）或皮质醇分泌肿瘤中；等待放射技术最大疗效时；治疗隐匿性 ACTH 产生肿瘤患者的严重皮质醇增多症时；或作为严重合并症患者的术前治疗。虽然超过 50%的病例可以实现生化“控制”，但此类药物的日常管理可能具有挑战性。事实上，采用“剂量滴定”或“阻断和替代”方法，定义正常皮质醇水平通常很困难，需要测量几种生物标志物。此外，每种药物都有其自身的副作用，必须密切监测。这种“患者处理方法”旨在阐明 4 种甾体激素合成抑制剂（酮康唑、左酮康唑、美替拉酮、奥西罗地司他）治疗皮质醇增多症的方法，以帮助内分泌科医生治疗库欣综合征患者。将讨论各种要点，如治疗的初始剂量、剂量方案、疗效监测和单药治疗的副作用。还将讨论甾体激素合成抑制剂的联合应用。
