Early shifts of adrenal steroid synthesis before and after relief of short-term cholestasis

Background/Aims: Chronic inflammatory diseases are characterised by a relat ive reduction of cortisol and adrenal androgens. The time point of appearan ce of these alterations is not known. Cholestasis may be a model of short-t erm inflammation to study early alterations of steroidogenesis. Methods: We investigated 18 patients with cholestasis before and after ther apeutic abolition of cholestasis (compared to nine control subjects, Co). Results: Serum tumour necrosis factor (TNF) was increased in cholestatic pa tients as compared to Co (P at least <0.01). Co as compared to cholestatic patients without tumours had elevated levels of plasma adrenocorticotropic hormone (ACTH) and serum dehydroepiandrosterone sulfate (DHEAS) but serum c ortisol levels were similar. Levels of ACTH and DHEAS in relation to serum IL-6 or TNF were higher in Co as compared to the cholestatic subgroup witho ut tumours, whereas serum cortisol in relation to these cytokines was simil ar. In both subgroups of cholestatic patients, we observed the typical infl ammation-dependent shift of adrenal hormones into the direction of cortisol in relation to DHEAS. Cholestatic patients with malignant tumours demonstr ated an intermediate response pattern. Conclusions: Short-term cholestasis for 5-12 days induced marked alteration s of adrenal steroidogenesis which partly resemble the changes observed in chronic inflammatory diseases. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.