Effects of chronic administration of PPAR-γ ligand rosiglitazone in Cushing's disease

Bruno Ambrosi, Chiara Dall'Asta, Salvatore Cannavò, Rosella Libè, Teresa Vigo, Paolo Epaminonda, Iacopo Chiodini, Stefano Ferrero, Francesco Trimarchi, Maura Arosio, Paolo Beck-Peccoz

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Rosiglitazone, a thiazolidinedione compound with peroxisome proliferator-activated receptor-γ (PPAR-γ -binding affinity, is able to suppress adrenocorticotropic hormone (ACTH) secretion in treated mice and in AtT20 pituitary tumor cells. These observations suggested that thiazolidinediones may be effective as therapy for Cushing's disease (CD). Patients and methods: Rosiglitazone (8 mg/day) was administered to 14 patients with active CD (13 women, one man, 18-68 years). Plasma ACTH, serum cortisol (F) and urinary free cortisol (UFC) levels were measured before and then monthly during rosiglitazone administration. Results: In six patients a reduction of ACTH and F levels and a normalization of UFC were observed 30-60 days after the beginning of rosiglitazone administration: there was a significant difference between basal and post-treatment values for UFC (1238±211 vs 154± 40 nmol/24 h, P <0.03), but not for ACTH (15.9±3.7 vs 7.9±0.9 pmol/l) and F levels (531±73 vs 344±58 nmol/l). Two of six cases, followed up for 7 months, showed a mild clinical improvement. Eight patients were nonresponders after 30-60 days of rosiglitazone treatment: their ACTH, F and UFC levels did not differ before and during drug administration. Immunohistochemical analysis of pituitary tumors removed from two responder and two nonresponder patients showed a similar intense immunoreactivity for PPAR-γ in about 50% of cells. Conclusions: The administration of rosiglitazone seems able to normalize cortisol secretion in some patients with CD, at least for short periods. Whether the activation of PPAR-γ by rosiglitazone might be effective as chronic pharmacologic treatment of CD needs a more extensive investigation through a randomized and controlled study.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalEuropean Journal of Endocrinology
Volume151
Issue number2
DOIs
Publication statusPublished - Aug 2004

ASJC Scopus subject areas

  • Endocrinology

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