Abstract | BACKGROUND: OBJECTIVE: Cluster analysis of the urinary steroid metabolome obtained by targeted gas chromatography-mass spectrometry (GC-MS) for treatment monitoring of children with CAH. METHODS: We evaluated 24-h urinary steroid metabolome analyses of 109 prepubertal children aged 7.0 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. 24-h urinary steroid metabolite excretions were transformed into CAH-specific z-scores. Subjects were divided into groups (metabotypes) by k-means clustering algorithm. Urinary steroid metabolome and clinical data of patients of each metabotype were analyzed. RESULTS: Four unique metabotypes were generated. Metabotype 1 (N = 21 (19%)) revealed adequate metabolic control with low cortisol metabolites (mean: -0.57z) and suppressed androgen and 17α-hydroxyprogesterone (17OHP) metabolites (-0.79z). Metabotype 2 (N = 23 (21%)) showed overtreatment consisting of a constellation of elevated urinary cortisol metabolites (0.62z) and low metabolites of androgens and 17OHP (-0.75z). Metabotype 3 (N = 32 (29%)) demonstrated undertreated patients with low cortisol metabolites (-0.69z) and elevated metabolites of androgens and 17OHP (0.50z). Metabotype 4 (N = 33 (30%)) presented patients with treatment failure reflected by unsuppressed androgen- and 17OHP metabolites (0.71z) despite elevated urinary cortisol metabolites (0.39z). CONCLUSION: Metabotyping, which means grouping metabolically similar individuals, helps to monitor treatment of children with CAH using GC-MS urinary steroid metabolome analysis. This method allows classification in adequately-, over-, or undertreated children as well as identification of patients with treatment failure.
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Authors | Clemens Kamrath, Michaela F Hartmann, Jörn Pons-Kühnemann, Stefan A Wudy |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 112
Pg. 154354
(11 2020)
ISSN: 1532-8600 [Electronic] United States |
PMID | 32916150
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents
- Fludrocortisone
- Hydrocortisone
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Topics |
- Adrenal Hyperplasia, Congenital
(drug therapy, urine)
- Anti-Inflammatory Agents
(therapeutic use)
- Child
- Child, Preschool
- Female
- Fludrocortisone
(therapeutic use)
- Gas Chromatography-Mass Spectrometry
- Humans
- Hydrocortisone
(therapeutic use)
- Male
- Metabolome
(physiology)
- Retrospective Studies
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