Merits and pitfalls of mifepristone in Cushing's syndrome

Author:

Castinetti F,Fassnacht M,Johanssen S,Terzolo M,Bouchard P,Chanson P,Do Cao C,Morange I,Picó A,Ouzounian S,Young J,Hahner S,Brue T,Allolio B,Conte-Devolx B

Abstract

ObjectiveMifepristone is the only available glucocorticoid receptor antagonist. Only few adult patients with hypercortisolism were treated to date by this drug. Our objective was to determine effectiveness and tolerability of mifepristone in Cushing's syndrome (CS).DesignRetrospective study of patients treated in seven European centers.MethodsTwenty patients with malignant (n=15, 12 with adrenocortical carcinoma, three with ectopic ACTH secretion) or benign (n=5, four with Cushing's disease, one with bilateral adrenal hyperplasia) CS were treated with mifepristone. Mifepristone was initiated with a median starting dose of 400 mg/day (200–1000). Median treatment duration was 2 months (0.25–21) for malignant CS, and 6 months (0.5–24) for benign CS. Clinical (signs of hypercortisolism, blood pressure, signs of adrenal insufficiency), and biochemical parameters (serum potassium and glucose) were evaluated.ResultsTreatment was stopped in one patient after 1 week due to severe uncontrolled hypokalemia. Improvement of clinical signs was observed in 11/15 patients with malignant CS (73%), and 4/5 patients with benign CS (80%). Psychiatric symptoms improved in 4/5 patients within the first week. Blood glucose levels improved in 4/7 patients. Signs of adrenal insufficiency were observed in 3/20 patients. Moderate to severe hypokalemia was observed in 11/20 patients and increased blood pressure levels in 3/20 patients.ConclusionMifepristone is a rapidly effective treatment of hypercortisolism, but requires close monitoring of potentially severe hypokalemia, hypertension, and clinical signs of adrenal insufficiency. Mifepristone provides a valuable treatment option in patients with severe CS when surgery is unsuccessful or impossible.

Publisher

Bioscientifica

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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