Existing treatments for pituitary-dependent Cushing's Syndrome include pituitary or adrenal surgery, pituitary irradiation and medical therapy. Pituitary microsurgery is the usual therapy of first choice but is not always successful in achieving early apparent remission and is associated with significant late relapses. An effective drug therapy for humans would be a major advance as there is significant morbidity and mortality in Cushing's Syndrome. Recent elegant in vitro and animal studies suggest that the PPAR-gamma receptor agonist rosiglitazone may be of use in pituitary-dependent Cushing's syndrome (1). We treated two patients with pituitary-dependent Cushing's syndrome with rosiglitazone 8mg daily for 33 and 20 days while they awaited pituitary microsurgery. The second patient was also treated with a steady dose of metyrapone (250mg qid) from five days before the rosiglitazone because of disease severity. The major assessment was made using sequential early morning cortisol to creatinine ratios, which closely correlate with 24h urinary cortisol measurements. No marked clinical change, side effects or hypoadrenalism was seen in either patient. In the first patient there were no significant changes in early morning urinary cortisol to creatinine ratios or circulating ACTH and cortisol day profiles, but there was a suggestion of a fall in urinary free cortisol (1581 and 2144 nanomols per 24 hours prior to and 1141 and 1099 nanomols per 24 hours by the final week of treatment). In the second patient early morning urinary cortisol to creatinine ratios decreased significantly from 474.1(115.2) during nine days from after the rapid initial fall with metyrapone had taken place to 348.1(115.4) in the final nine days of treatment, p=0.03. In conclusion our study shows a possible modest effect of rosiglitazone in Cushing's disease. Further carefully designed studies of dose and duration are required to confirm and define its possible role.
1.Heaney AP et al. Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nature Medicine 2002; 8(11): 1281-1287.
22 - 24 Mar 2004
British Endocrine Societies