Urinary GC–MS steroid metabotyping in treated children with congenital adrenal hyperplasia

• Published in: Metabolism, clinical and experimental Vol. 112; p. 154354
• Main Authors: Kamrath, Clemens, Hartmann, Michaela F., Pons-Kühnemann, Jörn, Wudy, Stefan A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Adrenal Hyperplasia, Congenital - drug therapy; Adrenal Hyperplasia, Congenital - urine; Anti-Inflammatory Agents - therapeutic use; Child; Child, Preschool; Congenital adrenal hyperplasia; Female; Fludrocortisone - therapeutic use; Gas Chromatography-Mass Spectrometry; GC–MS; Humans; Hydrocortisone - therapeutic use; Male; Metabolic control; Metabolome - physiology; Metabotyping; Retrospective Studies; Treatment monitoring; Urinary steroid metabolome; DHEA; Urinary steroid metabolome; PT; LLD; F; 21-DF; PTO; 6-OH-F; P; THE; THF; a-C; a-Cl; b-C; Metabotyping; Treatment monitoring; GC–MS; sPLS-DA; Metabolic control; ROC; 11OH-AN; CAH; IQR; AN; ET; 21OHD; PD; 11-O-AN; 17HP; b-Cl; 5-THF; Congenital adrenal hyperplasia; 17OHP; FC; 20-DHF
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2020.154354

Treatment of children with classic congenital adrenal hyperplasia (CAH) is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Cluster analysis of the urinary steroid metabolome obtained by targeted gas chromatography–mass spectrometry (GC–MS) for treatment monitoring of children with CAH. 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. 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). 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. •Treatment monitoring of children with CAH is not well defined•Cluster analysis of their urinary steroid metabolome obtained four unique metabotypes•Metabotyping allows classification in adequately-, over-, or undertreated patients•Metabotyping additionally identifies patients with treatment failure