The PPAR-gamma activator rosiglitazone fails to lower plasma ACTH levels in patients with Nelson's syndrome

Backround Peroxisomal proliferator-activated receptors (PPAR)-gamma are expressed abundantly in ACTH-secreting pituitary tumours. The PPAR-gamma activator rosiglitazone has been shown to suppress ACTH secretion in human adrenocorticotroph tumour cells in vitro, and prevent and reduce adrenocorticotroph tumour development in mouse models in vivo. Objective To evaluate the effect of rosiglitazone in patients with persistently elevated plasma ACTH levels postbilateral adrenalectomy for Cushing's disease. Patients Seven patients were treated with rosiglitazone 8 mg orally per day for 12 weeks. Measurements Plasma ACTH was measured at two hourly intervals from 09:00 h to 17:00 h before and after 6 and 12 weeks of treatment. Results Plasma ACTH at 09:00 hours immediately before the usual morning hydrocortisone dose was 2599(.)0 +/- 899(.)7 ng/l (mean +/- SEM) basally and 1547(.)6 +/- 515(.)7 ng/l after 12 weeks of rosiglitazone, whereas levels at 17:00 h were 1433(.)4 +/- 506(.)2 ng/l (mean +/- SEM) basally and 1122(.)3 +/- 460(.)9 ng/l at 12 weeks (all nonsignificant). Conclusion This study showed no effect of rosiglitazone treatment at maximum approved doses in lowering plasma ACTH levels in patients post bilateral adrenalectomy for Cushing's disease.