Exp Clin Endocrinol Diabetes 2004; 112 - P69
DOI: 10.1055/s-2004-819187

Effect of rosiglitazone treatment on central cushing syndrome

M Morcos 1, B Fohr 1, J Tafel 1, H Hammes 2, F Pfisterer 1, A Hamann 1, C Kasperk 1, P Humpert 1, G Rudofsky 1, A Sayed 1, A Bierhaus 1, PP Nawroth 1
  • 1Abt. Endokrinologie und Stoffwechsel, Universitätsklinik Heidelberg
  • 2Städtisches Klinikum Mannheim

Rosiglitazone (RG) belongs to he group of thiazolidindiones which are widely used in the treatment of type-2 diabetes. Beside blood-sugar lowering effects, RG has further biological properties, including antitumor effects. As recently shown in an animal model of ACTH-producing adenoma, RG suppressed ACTH secretion in human and murine corticotroph tumor cells and prevented development of corticotroph tumors. Aim of our study was to investigate possible effects of RG-treatment in humans with central cushing-syndrome.

So far, 10 patients with pituitary ACTH-excess were included. All of the patients underwent primary pituitary surgery and radiation, demonstrated persistent ACTH-oversecretion and would have been assigned to bilateral adrenalectomy in absence of other therapeutic options. All patients gave informed consent to the study. Heart insufficiency, anaemia and liver dysfunction were exclusion criteria and monitored regularly. ACTH and cortisol levels were monitored every 2–4 weeks. The initial dose of 4mg RG was increased to a maximal dose of 24mg RG, depending on the respond to treatment. MR-imaging was performed before and after 6 months of RG-treatment.

RG was generally well tolerated with the exception of the development of peripheral oedema in 3 patients, which could be well controlled by diuretics. After 5 months, cortisol levels (mean 350, normal range 50–250 ng/ml) dropped to normal range in all patients (mean 117 ng/ml). ACTH levels (mean 380, normal range 9–52 pg/ml) dropped markedly in all patients and reached normal range in 5 patients (mean 78 pg/ml). After 9 months, ACTH and cortisol levels started to increase again in 4 patients despite treatment with the maximum dose of RG. Until now, there was no effect of RG treatment on residual pituitary adenoma in MR-imaging.

Despite interesting animal data and surprising good initial response with respect to normalisation of biochemical abnormalities, we do not see a long lasting effect, at least in 4 out of 10 patients. Further studies of the effects of RG-treatment in cushing syndrome are required.