Service d'endocrinologie, diabète et maladies métaboliques, et Centre de référence des maladies rares d'origine hypophysaire DEFHY, Hôpital de la Timone, Marseille, France.
Neuroendocrinology. 2010;92 Suppl 1:125-30. doi: 10.1159/000314224. Epub 2010 Sep 10.
Mifepristone is the first and only available glucocorticoid receptor antagonist. It was initially mainly considered as a so-called 'contragestive' pill due to its antiprogestin activity. In this review, we summarize the results of mifepristone reported in the literature as a treatment of Cushing's syndrome. Most of the patients were treated due to unsuccessful surgery and/or partially effective anticortisolic drugs. The majority of them presented a rapid decrease of clinical signs of hypercortisolism during the first month of treatment; about half experienced a reduction in their elevated blood pressure, and half of the diabetic patients presented improved blood glucose levels. Mifepristone treatment has 2 main drawbacks: (1) the blockade of glucocorticoid receptors leads to increased ACTH and cortisol levels, making it difficult to adapt the treatment and diagnose adrenal deficiency, and (2) increased cortisol levels can also lead to severe hypokalemia. Follow-up of efficacy should only be clinical (weight, blood pressure, skin lesions) and biological (regular blood potassium sampling). Dose adjustment will be performed based on these parameters. The lack of a large available prospective cohort of patients on mifepristone, and the scarcity of data on its long-term effects, does not allow recommending it as a first-line drug in the treatment of hypercortisolism. However, as mifepristone is a rapidly effective drug, it can play a role in the management of hypercortisolism. The main indication is the partial efficacy or bad tolerance of other well-known anticortisolic drugs, either by replacement (bad tolerance, lack of effectiveness) or addition (multimodal approach) of mifepristone.
米非司酮是第一种也是唯一可用的糖皮质激素受体拮抗剂。最初，由于其抗孕激素活性，它主要被认为是一种所谓的“抗妊娠”药物。在这篇综述中，我们总结了文献中报道的米非司酮治疗库欣综合征的结果。大多数患者因手术失败和/或部分有效的皮质类固醇药物治疗而接受治疗。他们中的大多数人在治疗的第一个月内迅速减少了皮质醇过多的临床症状；约一半的患者血压降低，一半的糖尿病患者血糖水平改善。米非司酮治疗有两个主要缺点：（1）糖皮质激素受体的阻断导致 ACTH 和皮质醇水平升高，使得难以适应治疗和诊断肾上腺功能减退；（2）皮质醇水平的升高也可能导致严重的低钾血症。疗效的随访只能是临床的（体重、血压、皮肤病变）和生物学的（定期血钾采样）。根据这些参数进行剂量调整。缺乏大量可用于米非司酮的前瞻性队列患者，以及关于其长期效果的数据稀缺，不允许将其推荐为治疗皮质醇过多症的一线药物。然而，由于米非司酮是一种快速有效的药物，它可以在皮质醇过多症的管理中发挥作用。主要适应证是其他已知的皮质类固醇药物的部分疗效或不良耐受性，无论是通过替代（不良耐受性、缺乏疗效）还是添加（多模式方法）米非司酮。
