Background: Monitoring treatment of children with classic congenital adrenal hyperplasia (CAH) is difficult and biochemical targets are not well defined.
Objective and hypotheses: To analyse the urinary steroid metabolome of children with classic 21-hydroxylase deficiency (21-OHD) during treatment with hydrocortisone and fludrocortisone.
Method: We retrospectively analysed 553 daily urinary steroid hormone metabolite profiles determined by gas chromatography-mass spectrometry of 153 children aged 3.018.8 years with classic CAH on hydrocortisone and fludrocortisone treatment. Data of 24-h urinary steroid hormone metabolite analysis were included only once a year for every patient to avoid overrepresentation of single patients.
Results: Percentiles of the daily urinary excretion of glucocorticoid-, 17α-hydroxyprogesterone (17-OHP)-, and androgen metabolites were calculated for age groups in 2 year intervals for children with classic CAH aged 318 years. The urinary excretion of the sum of the seven major cortisol metabolites ranged in median from 6000 μg/m2 per day in toddlers to 9000 μg/m2 per day in adolescence and reflected 60.5±23.7% of the prescribed daily oral hydrocortisone dosage without influence of age or gender. Boys aged 13 and 14 years and girls aged 15 and 16 years showed a relatively unsuppressed adrenal when compared to their surrounding age groups, as they show a relatively high 17-OHP and androgen metabolite excretion. However, neither the prescribed daily hydrocortisone dosage nor the absolute excretions of cortisol metabolites were lower in these age groups. 11β-hydroxyandrosterone was the dominant urinary adrenal-derived androgen metabolite in CAH children, whereas urinary metabolites of DHEA were disproportionally suppressed by hydrocortisone treatment.
Conclusion: Values of urinary metabolite excretion rates of children with CAH are now available, allowing 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 could be important for research studies in children with CAH.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology