Successful Long-Term Treatment of Cushing Disease with Mifepristone (RU486)

ObjectiveWe describe a girl with Cushing disease for whom surgery and radiation treatments failed and the sub- sequent clinical course with mifepristone therapy.MethodsWe present the patient’s clinical, biochemi- cal, and imaging findings.ResultsA 16-year-old girl presented with classic Cushing disease. After transsphenoidal surgery, Cyberknife radiosurgery, ketoconazole, and metyrapone did not control her disease, and she was prescribed mifepristone, which was titrated to a maximal dosage of 1200 mg daily with subsequent symptom improvement. Mifepristone (RU486) is a high-affinity, nonselective antagonist of the glucocor- ticoid receptor. There is limited literature on its use as an off-label medication to treat refractory Cushing disease. Over her 8-year treatment with mifepristone, her therapy was complicated by hypertension and hypokalemia requir- ing spironolactone and potassium chloride. She received a 2-month drug holiday every 4 to 6 months to allow for withdrawal menstrual bleeding with medroxyprogester- one acetate. Urinary cortisol, serum cortisol, and cortico- tropin levels remained elevated during mifepristone drug holidays. While on mifepristone, her signs and symptoms of Cushing disease resolved. Repeated magnetic resonance imaging demonstrated stable appearance of the residual pituitary mass. Bilateral adrenalectomy was performed, and mifepristone was discontinued after 95 months of medical therapy.ConclusionsWe describe the longest duration of mifepristone therapy thus reported for the treatment of refractory Cushing disease. Mifepristone effectively controlled all signs and symptoms of hypercortisolism. Menstruating women who take the drug on a long-term basis should receive periodic drug holidays to allow for menses. The lack of reliable serum biomarkers to monitor the success of mifepristone therapy requires careful clini- cal judgment and may make its use difficult in Cushing disease. (Endocr Pract. 2012;18:e114-e120)