Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486)

An extremely ill patient, with Cushing's syndrome caused by an ACTH-secreti ng pituitary macroadenoma, experienced complications of end-stage cardiomyo pathy, profound psychosis, and multiple metabolic disturbances. Initially t reated unsuccessfully by a combination of conventional surgical, medical, a nd radiotherapeutic approaches, he responded dramatically to high-dose long -term mifepristone therapy (up to 25 mg/kg.d). Treatment efficacy was confi rmed by the normalization of all biochemical glucocorticoid-sensitive measu rements, as well as by the significant reversal of the patient's heart fail ure, the resolution of his psychotic depression, and the eventual unusual r eturn of his adrenal axis to normal His 18-month-long mifepristone treatmen t course was notable for development of severe hypokalemia that was attribu ted to excessive cortisol activation of the mineralocorticoid receptor, whi ch responded to spironolactone administration. This case illustrates the ef ficacy of high-dose long-term treatment with mifepristone in refractory Cus hing's syndrome. The case also demonstrates the potential need for concomit ant mineralocorticoid receptor blockade in mifepristone-treated Cushing's d isease, because cortisol levels may rise markedly, reflecting corticotroph disinhibition, to cause manifestations of mineralocorticoid excess.