Hypercortisolism in patients with cholestasis is associated with disease severity

作者：Verena Theiler‐Schwetz, Hansjörg Schlager, Barbara Obermayer‐Pietsch, Tatjana Stojaković, Günter Fauler, Peter Fickert, Gernot Zollner · 发表于：BMC Gastroenterology · 年份：2021 · DOI：10.1186/s12876-021-02045-4 · 被引用次数：4 · 研究领域：Drug Transport and Resistance Mechanisms、Liver Diseases and Immunity、Pediatric Hepatobiliary Diseases and Treatments

BACKGROUND: Cholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis. METHODS: Adrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry. RESULTS: Patients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated...