Friday, March 20, 2009

Merits and pitfalls of mifepristone in Cushing's syndrome

From http://www.eje.org/cgi/content/abstract/EJE-09-0098v1

European Journal of Endocrinology (2009) In press
DOI: 10.1530/EJE-09-0098
Copyright © 2009 by European Society of Endocrinology

Frederic Castinetti, Martin Fassnacht, Sarah Johanssen, Massimo Terzolo, Philippe Bouchard, Philippe Chanson, Christine DoCao, Isabelle Morange, Antonio Pico, Sophie Ouzounian, Jacques Young, Stephanie Hahner, Thierry Brue, Bruno Allolio and Bernard Conte-Devolx

F Castinetti, Department of Endocrinology, La Timone Hospital, Marseille, France
M Fassnacht, Dept. of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Josef-Schneider-Str. 2, Wuerzburg, Germany
S Johanssen, Dept. of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Josef-Schneider-Str. 2, Wuerzburg, Germany
M Terzolo, Dipartimento di Scienze Cliniche e Biologiche, Medicina Interna I, Orbassano, Italy, Orbassano, Italy
P Bouchard, Service d'Endocrinologie, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, FR-75571 Paris Cedex 12 France, Paris, France
P Chanson, Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Paris, France
C DoCao, Clinique Endocrinologique Marc Linquette, CHU, 59037 Lille-Cedex, Lille, France
I Morange, Department of Endocrinology, La Timone Hospital, Marseille, France
A Pico, Servicio de Endocrinología y Nutrición. Hospital General Universitario de Alicante, Alicante, Spain, Alicante, Spain
S Ouzounian, Service d'Endocrinologie, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, FR-75571 Paris Cedex 12 France, Paris, France
J Young, Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Paris, France
S Hahner, Dept. of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Josef-Schneider-Str. 2, Wuerzburg, Germany
T Brue, Department of Endocrinology, La Timone Hospital, Marseille, France
B Allolio, Dept. of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Josef-Schneider-Str. 2, Wuerzburg, Germany
B Conte-Devolx, Department of Endocrinology, La Timone Hospital, Marseille, France

Correspondence: Frederic Castinetti, Email: CastiFred1@free.fr

Objective: Mifepristone 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.

Design: Retrospective study of patients treated in seven European centers.

Methods: Twenty patients with malignant (n=15, 12 with adrenocortical carcinoma, 3 with ectopic ACTH secretion) or benign (n=5, 4 with Cushing's disease, 1 with bilateral adrenal hyperplasia) Cushing's syndrome (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.

Results: Treatment was stopped in 1 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.

Conclusion: Mifepristone 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.