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- Title:
Steroid synthesis inhibition with ketoconazole and its effect upon the regulation of the hypothalamus-pituitary-adrenal system in healthy humans.
- Document type:
- Journal Article; Article
- Author(s):
- Deuschle, M; Lecei, O; Stalla, GK; Landgraf, R; Hamann, B; Lederbogen, F; Uhr, M; Luppa, P; Maras, A; Colla, M; Heuser, I
- 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: 45.1+/-43.5; pre: 14.2+/-5.2 pmol/l; F(1,8)=9.78, p<0.02) and CBG concentrations (post: 38.8+/-4.3; pre: 31.9+/-4.2 microg/l), but DHEA-S plasma concentrations declined (post: 1.75+/-1.83; pre: 2.75+/-2.80 mg/l; F(1,8)=7.9, p<0.03). CRH concentrations in CSF were unchanged after treatment (post: 62.5+/-15.9; pre: 63.7+/-13.9 pg/ml), while there was a trend for AVP concentrations to rise during treatment (post: 2.52+/-1.18; pre: 1.92+/-0.96 pg/ml; paired t=-1.9, p<0.1). Cortisol CSF concentrations declined in the elderly (pre: 52.5+/-23.2; post: 26.7+/-4.6 nmol/l), but not in the young subgroup (pre: 15.6+/-11.3; post: 27.7+/-9.4 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.
- Journal title abbreviation:
- Neuropsychopharmacology
- Year:
- 2003
- Journal volume:
- 28
- Journal issue:
- 2
- Pages contribution:
- 379-83
- Language:
- eng
- Fulltext / DOI:
- doi:10.1038/sj.npp.1300044
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/12589391
- Print-ISSN:
- 0893-133X
- TUM Institution:
- Institut für Klinische Chemie und Pathobiochemie
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