A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion...

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Autores principales: Pařízek, Antonín, Hill, Martin, Dušková, Michaela, Vítek, Libor, Velíková, Marta, Kancheva, Radmila, Šimják, Patrik, Koucký, Michal, Kokrdová, Zuzana, Adamcová, Karolína, Černý, Andrej, Hájek, Zdeněk, Stárka, Luboslav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975406/
https://www.ncbi.nlm.nih.gov/pubmed/27494119
http://dx.doi.org/10.1371/journal.pone.0159203
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author Pařízek, Antonín
Hill, Martin
Dušková, Michaela
Vítek, Libor
Velíková, Marta
Kancheva, Radmila
Šimják, Patrik
Koucký, Michal
Kokrdová, Zuzana
Adamcová, Karolína
Černý, Andrej
Hájek, Zdeněk
Stárka, Luboslav
author_facet Pařízek, Antonín
Hill, Martin
Dušková, Michaela
Vítek, Libor
Velíková, Marta
Kancheva, Radmila
Šimják, Patrik
Koucký, Michal
Kokrdová, Zuzana
Adamcová, Karolína
Černý, Andrej
Hájek, Zdeněk
Stárka, Luboslav
author_sort Pařízek, Antonín
collection PubMed
description Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.
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spelling pubmed-49754062016-08-25 A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy Pařízek, Antonín Hill, Martin Dušková, Michaela Vítek, Libor Velíková, Marta Kancheva, Radmila Šimják, Patrik Koucký, Michal Kokrdová, Zuzana Adamcová, Karolína Černý, Andrej Hájek, Zdeněk Stárka, Luboslav PLoS One Research Article Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP. Public Library of Science 2016-08-05 /pmc/articles/PMC4975406/ /pubmed/27494119 http://dx.doi.org/10.1371/journal.pone.0159203 Text en © 2016 Pařízek et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pařízek, Antonín
Hill, Martin
Dušková, Michaela
Vítek, Libor
Velíková, Marta
Kancheva, Radmila
Šimják, Patrik
Koucký, Michal
Kokrdová, Zuzana
Adamcová, Karolína
Černý, Andrej
Hájek, Zdeněk
Stárka, Luboslav
A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy
title A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy
title_full A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy
title_fullStr A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy
title_full_unstemmed A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy
title_short A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy
title_sort comprehensive evaluation of steroid metabolism in women with intrahepatic cholestasis of pregnancy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975406/
https://www.ncbi.nlm.nih.gov/pubmed/27494119
http://dx.doi.org/10.1371/journal.pone.0159203
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