Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane

Trilostane is thought to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase (3β-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependan...

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Bibliographic Details
Published in:Domestic animal endocrinology 2006-07, Vol.31 (1), p.63-75
Main Authors: Sieber-Ruckstuhl, N.S., Boretti, F.S., Wenger, M., Maser-Gluth, C., Reusch, C.E.
Format: Article
Language:English
Subjects:
17-alpha-Hydroxypregnenolone - blood
3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors
Adrenocortical Hyperfunction - blood
Adrenocortical Hyperfunction - drug therapy
Adrenocortical Hyperfunction - veterinary
Adrenocorticotropic Hormone - blood
Aldosterone - blood
Androstenedione - blood
Animals
Cortodoxone - blood
Dehydroepiandrosterone - blood
Dihydrotestosterone - analogs & derivatives
Dihydrotestosterone - therapeutic use
Dog Diseases - blood
Dog Diseases - drug therapy
Dogs
Endogenous ACTH
Enzyme Inhibitors - therapeutic use
Female
Hydrocortisone - blood
Hyperadrenocorticism
Male
Prospective Studies
Statistics, Nonparametric
Steroid hormone concentrations
Trilostane
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Summary:Trilostane is thought to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase (3β-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependant hyperadrenocorticism (PDH). The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17α-OH-pregnenolone, dehydroepiandrostenedione) and after (17α-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1 h after injection of synthetic ACTH prior to ( t 0), in weeks 1–2 ( t 1) and in weeks 3–7 ( t 2) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test. During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17α-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase. The significant increase in 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3β-HSD. Since 17α-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11β-hydroxylase and possibly the 11β-hydroxysteroid dehydrogenase.
ISSN:0739-7240
1879-0054
DOI:10.1016/j.domaniend.2005.09.004