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

Clin Endocrinol (Oxf). 2006 May;64(5):519-22. doi: 10.1111/j.1365-2265.2006.02501.x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Adrenocorticotropic Hormone / blood*
  • Adult
  • Drug Administration Schedule
  • Humans
  • Middle Aged
  • Nelson Syndrome / blood*
  • Nelson Syndrome / metabolism
  • PPAR gamma / metabolism*
  • Pituitary ACTH Hypersecretion / metabolism
  • Pituitary ACTH Hypersecretion / surgery
  • Rosiglitazone
  • Statistics, Nonparametric
  • Thiazolidinediones / therapeutic use*
  • Time Factors
  • Treatment Failure

Substances

  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Adrenocorticotropic Hormone