Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study

Abstract BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers are at risk of presenting acute life-threatening neurovisceral attacks. The disease induces overpr...

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Autores: Pozo, Oscar J., Marcos, Josep, Fabregat, Andreu, Ventura, Rosa, Casals Mercadal, Gregori, Aguilera, Paula, Segura, Jordi, To i Figueras, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/118685
Acceso en línea:https://hdl.handle.net/2445/118685
Access Level:acceso abierto
Palabra clave:Porfíria
Hormones esteroides
Endocrinologia
Malalties rares
Porphyria
Steroid hormones
Endocrinology
Rare diseases
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spelling Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control studyPozo, Oscar J.Marcos, JosepFabregat, AndreuVentura, RosaCasals Mercadal, GregoriAguilera, PaulaSegura, JordiTo i Figueras, JordiPorfíriaHormones esteroidesEndocrinologiaMalalties raresPorphyriaSteroid hormonesEndocrinologyRare diseasesAbstract BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers are at risk of presenting acute life-threatening neurovisceral attacks. The disease induces overproduction of heme precursors in the liver and long-lasting deregulation of metabolic networks. The clinical history of AIP suggests a strong endocrine influence, being neurovisceral attacks more common in women than in men and very rare before puberty. To asses the hypothesis that steroidogenesis may be modified in AIP patients with biochemically active disease, we undertook a comprehensive analysis of the urinary steroid metabolome. METHODS: A case-control study was performed by collecting spot morning urine from 24 AIP patients and 24 healthy controls. Steroids in urine were quantified by liquid chromatography-tandem mass spectrometry. Parent steroids (17-hydroxyprogesterone; deoxycorticosterone; corticoesterone; 11-dehydrocorticosterone; cortisol and cortisone) and a large number of metabolites (N = 55) were investigated. Correlations between the different steroids analyzed and biomarkers of porphyria biochemical status (urinary heme precursors) were also evaluated. The Mann-Whitney U test and Spearman's correlation with a two tailed test were used for statistical analyses. RESULTS: Forty-one steroids were found to be decreased in the urine of AIP patients (P < 0.05), the decrease being more significant for steroids with a high degree of hydroxylation. Remarkably, 13 cortisol metabolites presented lower concentrations among AIP patients (P < 0.01) whereas no significant differences were found in the main metabolites of cortisol precursors. Nine cortisol metabolites showed a significant negative correlation with heme precursors (p < 0.05). Ratios between the main metabolites of 17-hydroxyprogesterone and cortisol showed positive correlations with heme-precursors (correlation coefficient > 0.51, P < 0.01). CONCLUSIONS: Comprehensive study of the urinary steroid metabolome showed that AIP patients present an imbalance in adrenal steroidogenesis, affecting the biosynthesis of cortisol and resulting in decreased out-put of cortisol and metabolites. This may result from alterations of central origin and/or may originate in specific decreased enzymatic activity in the adrenal gland. An imbalance in steroidogenesis may be related to the maintenance of an active disease state among AIP patients.BioMed Central2017201720142017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/118685Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/1750-1172-9-54.Orphanet Journal of Rare Diseases, 2014, vol. 9, p. 54https://doi.org/10.1186/1750-1172-9-54.cc-by (c) Pozo, Oscar J. et al., 2014http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1186852026-05-29T05:05:01Z
dc.title.none.fl_str_mv Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
title Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
spellingShingle Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
Pozo, Oscar J.
Porfíria
Hormones esteroides
Endocrinologia
Malalties rares
Porphyria
Steroid hormones
Endocrinology
Rare diseases
title_short Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
title_full Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
title_fullStr Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
title_full_unstemmed Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
title_sort Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
dc.creator.none.fl_str_mv Pozo, Oscar J.
Marcos, Josep
Fabregat, Andreu
Ventura, Rosa
Casals Mercadal, Gregori
Aguilera, Paula
Segura, Jordi
To i Figueras, Jordi
author Pozo, Oscar J.
author_facet Pozo, Oscar J.
Marcos, Josep
Fabregat, Andreu
Ventura, Rosa
Casals Mercadal, Gregori
Aguilera, Paula
Segura, Jordi
To i Figueras, Jordi
author_role author
author2 Marcos, Josep
Fabregat, Andreu
Ventura, Rosa
Casals Mercadal, Gregori
Aguilera, Paula
Segura, Jordi
To i Figueras, Jordi
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Porfíria
Hormones esteroides
Endocrinologia
Malalties rares
Porphyria
Steroid hormones
Endocrinology
Rare diseases
topic Porfíria
Hormones esteroides
Endocrinologia
Malalties rares
Porphyria
Steroid hormones
Endocrinology
Rare diseases
description Abstract BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers are at risk of presenting acute life-threatening neurovisceral attacks. The disease induces overproduction of heme precursors in the liver and long-lasting deregulation of metabolic networks. The clinical history of AIP suggests a strong endocrine influence, being neurovisceral attacks more common in women than in men and very rare before puberty. To asses the hypothesis that steroidogenesis may be modified in AIP patients with biochemically active disease, we undertook a comprehensive analysis of the urinary steroid metabolome. METHODS: A case-control study was performed by collecting spot morning urine from 24 AIP patients and 24 healthy controls. Steroids in urine were quantified by liquid chromatography-tandem mass spectrometry. Parent steroids (17-hydroxyprogesterone; deoxycorticosterone; corticoesterone; 11-dehydrocorticosterone; cortisol and cortisone) and a large number of metabolites (N = 55) were investigated. Correlations between the different steroids analyzed and biomarkers of porphyria biochemical status (urinary heme precursors) were also evaluated. The Mann-Whitney U test and Spearman's correlation with a two tailed test were used for statistical analyses. RESULTS: Forty-one steroids were found to be decreased in the urine of AIP patients (P < 0.05), the decrease being more significant for steroids with a high degree of hydroxylation. Remarkably, 13 cortisol metabolites presented lower concentrations among AIP patients (P < 0.01) whereas no significant differences were found in the main metabolites of cortisol precursors. Nine cortisol metabolites showed a significant negative correlation with heme precursors (p < 0.05). Ratios between the main metabolites of 17-hydroxyprogesterone and cortisol showed positive correlations with heme-precursors (correlation coefficient > 0.51, P < 0.01). CONCLUSIONS: Comprehensive study of the urinary steroid metabolome showed that AIP patients present an imbalance in adrenal steroidogenesis, affecting the biosynthesis of cortisol and resulting in decreased out-put of cortisol and metabolites. This may result from alterations of central origin and/or may originate in specific decreased enzymatic activity in the adrenal gland. An imbalance in steroidogenesis may be related to the maintenance of an active disease state among AIP patients.
publishDate 2014
dc.date.none.fl_str_mv 2014
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/118685
url https://hdl.handle.net/2445/118685
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/1750-1172-9-54.
Orphanet Journal of Rare Diseases, 2014, vol. 9, p. 54
https://doi.org/10.1186/1750-1172-9-54.
dc.rights.none.fl_str_mv cc-by (c) Pozo, Oscar J. et al., 2014
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Pozo, Oscar J. et al., 2014
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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