ESPE2022 Poster Category 1 Adrenals and HPA Axis (52 abstracts)
Steroid metabotyping in treated infants with classical congenital adrenal hyperplasia by chromatography-mass spectrometry analysis
Objective: Cluster analysis of urinary steroid metabolome analysis obtained by gas chromatography-mass spectrometry (GC-MS) for treatment monitoring of infants with classic salt-wasting CAH.
Methods: We evaluated metabolome analysis of spot urine samples of 60 young children ≤4 years of age (29 females) with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. Subjects were divided into groups (metabotypes) by hierarchical clustering using the Euclidean distance and Ward's linkage algorithm.
Results: Three unique metabotypes were generated. Metabotype #1 (n=15 (25%)) showed high urinary androgen and 17OHP concentrations, metabotype #2 (n=28 (47%)) revealed adequate metabolic control, and metabotype #3 (n=17; 28%) demonstrated suppressed adrrenals. The metaboltypes did not differ in age, sex, weight and height. The daily hydrocortisone doses and urinary concentrations of cortisol and cortisone metabolites did not differ between all metabotypes. Metabotype #2 had highest daily dose of fludrocortisone (75±44 μg vs. 50±25 µg and 50±23 µg in metaboltypes #1 and #3, respectively; P=0.016). Receiver operating characteristic curve analysis showed that pregnanetriolone (11-O-PT, area under the curve (AUC) 0.967, cut-off 308 µg/L), pregnanetriol (PT, AUC 0.936, cut-off 731 µg/L) and the ratio PTO/ tetrahydrocortisone (THE) (AUC 0.899, cut-off 0.175) were most suitable of separating metabotype #1 from #2. For metabotypes #2 vs. #3, the 11-oxygenated androgen metabolite 11-hydroxyandrosterone (11-OH-AN, AUC 0.983, cut-off 24.2 µg/L), the ratio 11-OH-AN/ THE (AUC 0.97, cut-off 0.015) and PT (AUC 0.956, cut-off 194 µg/L) were most suitable.
Conclusion: Metabotyping helps to monitor treatment of infants with CAH. This method allows classification in under-, over-, and adequate-treated young children.
15 Sep 2022 - 17 Sep 2022