The Urinary Steroidome of Treated Children With Classic 21-Hydroxylase Deficiency
Abstract
Monitoring treatment of children with classic congenital adrenal hyperplasia (CAH) is difficult and biochemical targets are not well defined. We retrospectively analysed 576 daily urinary steroid hormone metabolite profiles determined by gas chromatography-mass spectrometry of 150 children aged 3.0-17.9 years with classic 21-hydroxylase deficiency (21-OHD) on hydrocortisone and fludrocortisone treatment. Daily urinary excretion of glucocorticoid-, 17α-hydroxyprogesterone (17-OHP)-, and androgen metabolites as well as growth and weight gain are presented. Children with classic CAH exhibited increased height velocity during prepubertal age, which was then followed by diminished growth velocity during pubertal age until final height was reached. Final height was clearly below the population mean. 11β-Hydroxyandrosterone was the dominant urinary adrenal-derived androgen metabolite in CAH children. Adrenarche is blunted in children with CAH under hydrocortisone treatment and androgen metabolites except 11β-hydroxyandrosterone were suppressed. Cortisol metabolite excretion reflected supraphysiological hydrocortisone treatment dosage, which resulted in higher body-mass-indices in children with CAH. Reference values of daily urinary steroid metabolite excretions of treated children with CAH allow the clinician to adequately classify the individual patient regarding the androgen-, 17-OHP-, and glucocorticoid status in the context of the underlying disorder. Additionally, urinary 21-OHD-specific reference ranges will be important for research studies in children with CAH.
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11-oxyandrogens, including 11OHA4 and 11KT, have been shown to be elevated in patients with classic and non-classic 21OHD.
“In particular, a set of 11-oxygenated-C19 steroids (11-oxyandrogens), including 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT), have been shown to be elevated in patients with classic (12, 15) and non-classic 21OHD (16).”
From 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency (2021) · cites this paper as [15]
The conventional steroid panel of patients with 21OHD has been expanded in recent years to include previously neglected androgens.
“The conventional steroid panel of patients with 21OHD has been expanded in the recent years, to include previously neglected androgens (12–14).”
From 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency (2021) · cites this paper as [14]
Timed samples (e.g. 24-hr urine) provide additional information on hormonal production rates via determination of steroid excretion rates.
“Timed samples (e.g.24-hr urine) provide additional information on hormonal production rates via determination of steroid excretion rates (296,297).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [296]
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- Authors
- Kamrath, C., Wettstaedt, L., Boettcher, C., Hartmann, M. F., & Wudy, S. A.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Corresponding author
- Wudy, Stefan A.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 165
- Issue
- Pt B
- Pages
- 396-406
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2516425617
- Cited by
- 30
- References
- 39
- Citations by year
- 2024: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 4
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital adrenal hyperplasia, urinary steroid metabolites, cortisol, fludrocortisone, 17-hydroxyprogesterone, adrenal androgens, growth rate, adult height, adrenarche, cortisol metabolites, body mass index, reference values, children
- MeSH terms
- Adolescent, Adrenal Hyperplasia, Congenital, Androgens, Androsterone, Body Height, Body Weight, Child, Child, Preschool, Female, Fludrocortisone, Glucocorticoids, Humans, Hydrocortisone, Male, Gas Chromatography-Mass Spectrometry, Reference Values, Retrospective Studies, Steroid 21-Hydroxylase, Steroids, Cohort Studies, Urinalysis, Adrenarche
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