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

Background/Aims: Chronic inflammatory diseases are characterised by a relative reduction of cortisol and adrenal androgens. The time point of appearance of these alterations is not known. Cholestasis may be a model of short-term inflammation to study early alterations of steroidogenesis. Methods: We investigated 18 patients with cholestasis before and after therapeutic abolition of cholestasis (compared to nine control subjects, Co). Results: Serum tumour necrosis factor (TNF) was increased in cholestatic patients 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 cortisol 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 without tumours, whereas serum cortisol in relation to these cytokines was similar. In both subgroups of cholestatic patients, we observed the typical inflammation-dependent shift of adrenal hormones into the direction of cortisol in relation to DHEAS. Cholestatic patients with malignant tumours demonstrated an intermediate response pattern. Conclusions: Short-term cholestasis for 5–12 days induced marked alterations of adrenal steroidogenesis which partly resemble the changes observed in chronic inflammatory diseases.