24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency

BackgroundOptimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking.ObjectiveTo compare the dynamic r...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adina F. Turcu, Ashwini Mallappa, Aikaterini A. Nella, Xuan Chen, Lili Zhao, Aya T. Nanba, James Brian Byrd, Richard J. Auchus, Deborah P. Merke
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	21-hydroxylase deficiency congenital adrenal hyperplasia 11-oxyandrogens Circadian hormones cortisol 24-hour profile CAH Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/e678b04d9d664e889f9b3bec448def53
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e678b04d9d664e889f9b3bec448def53
record_format	dspace
spelling	oai:doaj.org-article:e678b04d9d664e889f9b3bec448def532021-11-16T07:38:23Z24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency1664-239210.3389/fendo.2021.751191https://doaj.org/article/e678b04d9d664e889f9b3bec448def532021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.751191/fullhttps://doaj.org/toc/1664-2392BackgroundOptimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking.ObjectiveTo compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling.Participants and MethodsWe studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I–II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI.ResultsIn response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men.Conclusion11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.Adina F. TurcuAshwini MallappaAikaterini A. NellaXuan ChenLili ZhaoAya T. NanbaJames Brian ByrdRichard J. AuchusRichard J. AuchusDeborah P. MerkeDeborah P. MerkeFrontiers Media S.A.article21-hydroxylase deficiencycongenital adrenal hyperplasia11-oxyandrogensCircadian hormonescortisol 24-hour profileCAHDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	21-hydroxylase deficiency congenital adrenal hyperplasia 11-oxyandrogens Circadian hormones cortisol 24-hour profile CAH Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	21-hydroxylase deficiency congenital adrenal hyperplasia 11-oxyandrogens Circadian hormones cortisol 24-hour profile CAH Diseases of the endocrine glands. Clinical endocrinology RC648-665 Adina F. Turcu Ashwini Mallappa Aikaterini A. Nella Xuan Chen Lili Zhao Aya T. Nanba James Brian Byrd Richard J. Auchus Richard J. Auchus Deborah P. Merke Deborah P. Merke 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
description	BackgroundOptimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking.ObjectiveTo compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling.Participants and MethodsWe studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I–II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI.ResultsIn response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men.Conclusion11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.
format	article
author	Adina F. Turcu Ashwini Mallappa Aikaterini A. Nella Xuan Chen Lili Zhao Aya T. Nanba James Brian Byrd Richard J. Auchus Richard J. Auchus Deborah P. Merke Deborah P. Merke
author_facet	Adina F. Turcu Ashwini Mallappa Aikaterini A. Nella Xuan Chen Lili Zhao Aya T. Nanba James Brian Byrd Richard J. Auchus Richard J. Auchus Deborah P. Merke Deborah P. Merke
author_sort	Adina F. Turcu
title	24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
title_short	24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
title_full	24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
title_fullStr	24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
title_full_unstemmed	24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
title_sort	24-hour profiles of 11-oxygenated c19 steroids and δ5-steroid sulfates during oral and continuous subcutaneous glucocorticoids in 21-hydroxylase deficiency
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e678b04d9d664e889f9b3bec448def53
work_keys_str_mv	AT adinafturcu 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT ashwinimallappa 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT aikaterinianella 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT xuanchen 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT lilizhao 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT ayatnanba 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT jamesbrianbyrd 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT richardjauchus 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT richardjauchus 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT deborahpmerke 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency AT deborahpmerke 24hourprofilesof11oxygenatedc19steroidsandd5steroidsulfatesduringoralandcontinuoussubcutaneousglucocorticoidsin21hydroxylasedeficiency
_version_	1718426639187050496

24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency

Ejemplares similares