BACKGROUND: 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 .
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 7.0â¯±â¯1.6â¯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 (Nâ¯=â¯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 (Nâ¯=â¯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 (Nâ¯=â¯32 (29 %) ) demonstrated undertreated patients with low cortisol metabolites (-0.69z) and elevated metabolites of androgens and 17OHP (0.50z). Metabotype 4 (Nâ¯=â¯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.