A new therapeutic approach in the medical treatment of Cushing's syndrome: glucocorticoid receptor blockade with mifepristone.

OBJECTIVE: Cushing's syndrome (CS) is a serious endocrine disorder caused by prolonged exposure to high cortisol levels. Initial treatment of this condition is dependent upon the cause, but is generally surgical. For patients whose hypercortisolism is not cured by surgery, medical therapy is often required. Drugs that have typically been used for CS medical therapy act by decreasing cortisol levels. Mifepristone is a glucocorticoid receptor antagonist now available for use in patients with CS. Unlike other agents, mifepristone does not decrease cortisol levels, but directly antagonizes its effects. Our objective is to review the pharmacology and clinical use of this novel agent and to discuss detailed guidance on the management of CS patients treated with mifepristone.
METHODS: We review the literature regarding mifepristone use in CS and recently published clinical trial data. Detailed information related to clinical assessment of mifepristone use, potential drug interactions, drug initiation and dose titration, and monitoring of drug tolerability are provided.
RESULTS: Clinical trial data have shown that mifepristone improves glycemic control and blood pressure, causes weight loss and a decrease in waist circumference, lessens depression, and improves overall wellbeing. However, adverse effects include adrenal insufficiency, hypokalemia, and endometrial thickening with vaginal bleeding. These findings are supported by the earlier literature case reports.
CONCLUSION: This article provides a review of the pharmacology and clinical use of mifepristone in Cushing's syndrome, as well as detailed guidance on the management of patients treated with this novel agent.