1. ¹Central Institute of Mental Health, Mannheim, Germany
2. ²Max Planck Institute of Psychiatry, Munich, Germany
3. ³Institute of Clinical Chemistry & Pathobiochemistry, Technical University, Munich, Germany
4. ⁴Department of Psychiatry, Free University of Berlin, Germany

Correspondence: Dr M Deuschle, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. Tel: +49 621 1703 626; Fax: +49 621 1703 891; E-mail: deuschle@as200.zi-mannheim.de

^*This study was supported by a grant of the Deutsche Forschungsgemeinschaft to MD and IH (DFG De 660/4-1).

Received 24 February 2002; Revised 22 July 2002; Accepted 24 July 2002.

Abstract

Steroid synthesis inhibitors are commonly used in the treatment of patients with Cushing's disease, but may also improve psychopathology in hypercortisolemic depressed patients. Since glucocorticoids exert a negative feedback at pituitary and supra-pituitary levels, the inhibition of steroid synthesis may lead to increased expression of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). We studied the effect of treatment with 800 mg ketoconazole (3 weeks) upon the concentrations of basal plasma cortisol in the evening, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S), and ACTH as well as the concentrations of cortisol, CRH, and AVP in cerebrospinal fluid (CSF) at 8.30 h in 10 healthy, male volunteers. While we found cortisol plasma concentrations to be unchanged, we noted a significant increase in ACTH (post: 45.143.5; pre: 14.25.2 pmol/l; F_1,8=9.78, p<0.02) and CBG concentrations (post: 38.84.3; pre: 31.94.2 g/l), but DHEA-S plasma concentrations declined (post: 1.751.83; pre: 2.752.80 mg/l; F_1,8=7.9, p<0.03). CRH concentrations in CSF were unchanged after treatment (post: 62.515.9; pre: 63.713.9 pg/ml), while there was a trend for AVP concentrations to rise during treatment (post: 2.521.18; pre: 1.920.96 pg/ml; paired t=-1.9, p<0.1). Cortisol CSF concentrations declined in the elderly (pre: 52.523.2; post: 26.74.6 nmol/l), but not in the young subgroup (pre: 15.611.3; post: 27.79.4 nmol/l). We thus conclude that the treatment of healthy controls with steroid-synthesis inhibitors does not lead to a major increase in CRH secretion.