Endocrine Abstracts

21-hydroxylase deficiency is by far (>90%) the most common cause of congenital adrenal hyperplasia (CAH). Undiagnosed and untreated 21-hydoxylase deficiency bears the risk of salt loss, adrenal insufficiency and sex misassignment, therefore early diagnosis is very important. The most common way to identify children affected by the enzyme defect is the measurement of blood levels of adrenal hormones and precursor steroids, which is an invasive method and may lead to inaccuracy due to maternal-placental and fetal steroid products. We analyzed the urinary steroid profiles in neonates and young infants by GC–MS at time of diagnosis. The aim of the study was to determine the most specific and sensitive parameters of 21-hydroxylase deficiency. Twenty-seven children diagnosed with classical form of 21-hydroxylase deficiency,(14 boys, 13 girls; average age 37 (2–125) days) were included in the study and were compared with 47 healthy children (25 boys, 22 girls; average age 43 (0–144) days). Random urine samples were analyzed for steroid hormone metabolites and precursor/product ratios were calculated. Fetal zone steroids and cortisone metabolites were not discriminating. Indicators for 21-hydroxylase deficiency were: 15β,17α-dihydroxy-pregnanolone (15β,17α-OH-Po), pregnanetriol (PT), 11-O-pregnanetriol (11-O-PT), 5α,3α-pregnanolone (Po-5α,3α), 5β,3α-pregnanolone (Po-5β,3α). All parameters discriminated between CAH patients and healthy children by 100%. Differences were most expressed regarding 11-O-pregnanetriol.

Precursor/product ratios did not give more information to detect affected children. The advantage of urinary GC–MS analysis is that it is non-invasive and that it permits rapid and definitive diagnosis of 21-hydroxylase deficiency.