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

BACKGROUND: 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.