Ineffectiveness of rosiglitazone therapy in Nelson's syndrome.
BACKGROUND
Peroxisome proliferator-activated receptor (PPAR)-gamma 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.


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


METHODS
The study was conducted at a university teaching hospital.


METHODS
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-gamma immunoreactivity was assessed in pathological tissue.


METHODS
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-gamma immunoreactivity was positive in three ACTH-secreting tumors available.


CONCLUSIONS
Rosiglitazone 12 mg/d did not change circulating ACTH over time, despite PPAR-gamma 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.
Munir
A
A
Academic Unit of Diabetes, Endocrinology, and Metabolism, The University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield, United Kingdom.
Song
F
F
Ince
P
P
Walters
S J
SJ
Ross
R
R
Newell-Price
J
J
D049913:ACTH-Secreting Pituitary Adenoma / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D009347:Nelson Syndrome / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D047495:PPAR gamma / Q000096:biosynthesis / Q000187:drug effects; D010195:Pancreatitis / Q000150:complications; D047748:Pituitary ACTH Hypersecretion / Q000150:complications; D010902:Pituitary Gland / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D010911:Pituitary Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000324:Adrenocorticotropic Hormone; D005438:Fludrocortisone; D006854:Hydrocortisone