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Hypercortisolism in patients with cholestasis is associated with disease severity
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), b...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650422/ https://www.ncbi.nlm.nih.gov/pubmed/34876016 http://dx.doi.org/10.1186/s12876-021-02045-4 |
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author | Theiler-Schwetz, Verena Schlager, Hansjörg Obermayer-Pietsch, Barbara Stojakovic, Tatjana Fauler, Günter Fickert, Peter Zollner, Gernot |
author_facet | Theiler-Schwetz, Verena Schlager, Hansjörg Obermayer-Pietsch, Barbara Stojakovic, Tatjana Fauler, Günter Fickert, Peter Zollner, Gernot |
author_sort | Theiler-Schwetz, Verena |
collection | PubMed |
description | 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 bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels. CONCLUSIONS: We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance. |
format | Online Article Text |
id | pubmed-8650422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86504222021-12-07 Hypercortisolism in patients with cholestasis is associated with disease severity Theiler-Schwetz, Verena Schlager, Hansjörg Obermayer-Pietsch, Barbara Stojakovic, Tatjana Fauler, Günter Fickert, Peter Zollner, Gernot BMC Gastroenterol Research 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 bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels. CONCLUSIONS: We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance. BioMed Central 2021-12-07 /pmc/articles/PMC8650422/ /pubmed/34876016 http://dx.doi.org/10.1186/s12876-021-02045-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Theiler-Schwetz, Verena Schlager, Hansjörg Obermayer-Pietsch, Barbara Stojakovic, Tatjana Fauler, Günter Fickert, Peter Zollner, Gernot Hypercortisolism in patients with cholestasis is associated with disease severity |
title | Hypercortisolism in patients with cholestasis is associated with disease severity |
title_full | Hypercortisolism in patients with cholestasis is associated with disease severity |
title_fullStr | Hypercortisolism in patients with cholestasis is associated with disease severity |
title_full_unstemmed | Hypercortisolism in patients with cholestasis is associated with disease severity |
title_short | Hypercortisolism in patients with cholestasis is associated with disease severity |
title_sort | hypercortisolism in patients with cholestasis is associated with disease severity |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650422/ https://www.ncbi.nlm.nih.gov/pubmed/34876016 http://dx.doi.org/10.1186/s12876-021-02045-4 |
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