Cortisol excess is associated with increased mortality from cardiovascular disease. In the general population this is now recognised as being common and is termed Sub-Clinical Cushing's Syndrome, is found frequently in patients with adrenal masses incidentally disclosed on CT scans, and is associated with higher cardiovascular risk including hypertension and impaired glucose tolerance and diabetes. Pre-clinical and clinical data in other areas suggest that antagonism of the glucocorticoid receptor will improve these parameters, and guide selection for adrenal surgery. We propose an open-label pilot study to investigate the effects of the glucocorticoid receptor antagonist mifepristone in this condition. Mifepristone is currently licensed for obstetric practice.

Outcome measures have been chosen that can predict clinical benefit, and that will allow an understanding of the nature and degree of the mechanism of effect. We propose to use oral mifepristone (200mg twice daily for 8 weeks), in one centre (Sheffield) to assess its effect in these patients. Primary endpoints will be resting and 24 hour ambulatory systolic blood pressure (BP) and 2-hour glucose on oral glucose tolerance testing at 8 weeks.

Secondary end points at 4 and 8 weeks will be BP and glucose tolerance, insulin resistance and sensitivity, 0900h plasma ACTH/cortisol and salivary 0900/2400h cortisol values, and health related quality of life; secondary end points at 8 weeks will be fasting lipids, markers of bone turnover at 8 weeks, and urinary steroid profile (as determined by gas chromatography/mass spectrometry). A positive result of this study would be easy to translate into a larger clinical trial using mifepristone and also one including selection for laparoscopic adrenalectomy as a permanent therapy.