Endocrine Abstracts

Background

PPAR-gamma agonists have been proposed as therapy to lower plasma ACTH in Cushing's disease. However, cyclical secretion may explain some of the 'responses' seen. In contrast, patients with Nelson's syndrome have continual high ACTH levels, and can present with pituitary mass effects and pigmentation. Since no established medical therapy exists, we assessed whether prolonged high-dose rosiglitazone therapy reduces circulating ACTH levels in Nelson's syndrome.

Patients and Methods

Six patients with active Nelson's syndrome from Sheffield Teaching Hospitals endocrine clinics entered an open-label, prospective, non-randomised pilot study over 14 weeks. Plasma ACTH levels were >200ng/L after the morning dose of hydrocortisone (HC) in all studied. The study had ethical approval and patients gave written informed consent. Patients were assessed at minus2, 0, 4, 8 and 12 weeks. Rosiglitazone 12mg/day (max licensed dose for type II diabetes is 8mg/day) was administered between 0 and 8 weeks. At each assessment, plasma ACTH was measured before (0830h) and 120 minutes after, morning dosing with HC.

Results

One female withdrew prior to commencing therapy for personal reasons. The remaining five completed the study and tolerated the medication without complications. Baseline pre-HC ACTH was 1175.4 (plus/minus 198.6) ng/L, post HC ACTH was 372.6 (plus/minus 135) ng/L. Following 8 weeks of Rosiglitazone, pre-HC ACTH levels were 1200.7 (plus/minus 180.3) ng/L. and post HC ACTH levels were 439 (plus/minus 129) ng/L, with no statistically significant change in ACTH levels (p>0.05). PPAR gamma immunoreactivity was positive in two ACTH-secreting tumours assessed.

Conclusions

This is the first report of PPAR agonist therapy in Nelson's syndrome, and provides important dosing and safety information for design of future studies. Rosiglitazone at this dose is not effective therapy, despite presence of PPAR gamma in the tumour. However, even higher doses of rosiglitazone, or more potent agonists, might prove useful treatment in the future.