Background: One major issue of newborn screening programs for 21-hydroxylase deficiency (21OHD) is the high rate of false-positive results, especially in preterm neonates. Urinary steroid analysis using gas chromatographymass spectrometry (GCMS) is used as a confirmatory diagnostic tool.
Objective and Hypotheses: The objective of this study was to analyze diagnostic metabolite ratios in neonates and infants with and without 21OHD using GCMS with emphasis on glucocorticoid metabolism, and to publish reference values for the diagnosis of 21OHD in the largest cohort so far.
Method: We analyzed urinary steroid hormone profiles determined by GCMS of 95 untreated 21OHD neonates and infants (1148 days), and 261 neonates and infants (100 preterms) without 21OHD (0217 days).
Results: Metabolites of 17α-hydroxyprogesterone showed specificities below 98%, whereas the 21-deoxycortisol metabolite pregnanetriolone clearly separated 21OHD from non-21OHD subjects. The best diagnostic ratio for 21OHD was pregnanetriolone to 6α-hydroxy-tetrahydrocortisone. The lowest value of this ratio in the 21OHD group (0.47) was at least eight times higher than the highest values in the non-21OHD group (0.055).
Conclusion: We have given appropriate reference values for steroid metabolite ratios in the largest 21OHD cohort so far. Consideration of glucocorticoid metabolism, especially the use of typical neonatal 6α-hydroxylates metabolites, leads to improvement of diagnostic metabolite ratios.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology