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Ineffectiveness of Rosiglitazone Therapy in Nelson’s Syndrome

Academic Unit of Diabetes, Endocrinology, and Metabolism (A.M., F.S., R.R., J.N.-P.) and Neuropathology (P.I.), School of Medicine and Biomedical Sciences, Medical Statistics Group (S.J.W.), The University of Sheffield, Sheffield S10 2JF, United Kingdom

Address all correspondence and requests for reprints to: Dr. J. Newell-Price, Senior Lecturer and Consultant Endocrinologist, Academic Unit of Diabetes, Endocrinology, and Metabolism, The University of Sheffield, Room OU142, O Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, United Kingdom. E-mail: j.newellprice{at}sheffield.ac.uk.

Background: Peroxisome proliferator-activated receptor (PPAR)- agonists have been proposed as therapy to lower plasma ACTH in Cushing’s disease. Cyclical secretion of ACTH may, however, explain some of the responses seen. Patients with Nelson’s syndrome have persistently high levels of ACTH and may be a better model for examining new therapies to elevated ACTH levels.

Objective: The objective of the study was to assess whether high-dose rosiglitazone therapy reduces circulating ACTH levels in Nelson’s syndrome, a model of ACTH hypersecretion for which no established medical therapy exists.

Design: The design was an open-label, prospective, nonrandomized study over 14 wk.

Setting: The study was conducted at a university teaching hospital.

Patients: Six patients with Nelson’s syndrome participated in the study.

Methods: Patients were assessed at –2, 0, 4, 8, and 12 wk. Rosiglitazone 12 mg/d was administered between 0 and 8 wk. PPAR- immunoreactivity was assessed in pathological tissue.

Outcome Measure: Plasma ACTH was measured before (0830 h) and 120 min after morning dosing with hydrocortisone (HC).

Results: One female withdrew prior to commencing therapy for personal reasons. There was no evidence that ACTH levels changed over time (P = 0.864). The average ACTH level was 1187 ng/liter (95% confidence interval 928–1446) for patients before the HC dose and 432 ng/liter (95% confidence interval 172–692) after the HC dose. PPAR- immunoreactivity was positive in three ACTH-secreting tumors available.

Conclusions: Rosiglitazone 12 mg/d did not change circulating ACTH over time, despite PPAR- receptor expression in the tumor tissue. However, this does not preclude the possibility that other patients may respond or that higher doses of rosiglitazone or more potent agonists might prove useful treatment.

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