Genotype-refined 17OHP cut-offs diagnosing nonclassical CAH due to 21OH deficiency in children with premature pubarche.

Partial 21-hydroxylase deficiency due to biallelic CYP21A2 variants raises 17-hydroxyprogesterone, whose diagnostic thresholds can be calibrated against genotype.

Premature pubarche is a frequent reason for endocrine evaluation, and 5% to 20% of affected children have nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. This diagnostic accuracy study included 203 children (median age 7.5 years; 85% girls) who underwent ACTH stimulation testing, with CYP21A2 genotyping as the gold standard: 32 children (15.7%) had biallelic pathogenic variants. Basal 17-hydroxyprogesterone showed excellent diagnostic accuracy (AUC 0.98), a cut-off of 170 ng/dL (5.1 nmol/L) providing the best balance (97% sensitivity, 91% specificity), while 410 ng/dL (12.4 nmol/L) reached 100% specificity and a post-ACTH value above 1,104 ng/dL (33.4 nmol/L) reached 100% sensitivity and specificity. Androgen levels overlapped substantially and no clinical feature distinguished the two groups; the authors propose a dual basal threshold strategy that obviates ACTH testing.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This is the kind of paper that transfers directly to practice: a genotype-anchored basal 17-OHP threshold that spares stimulation testing in many children referred for premature pubarche. Two operational caveats: the cut-offs derive from a radioimmunoassay and are not transferable as such to automated immunoassays or mass spectrometry, and the cohort is single-centre with a 15.7% prevalence, higher than a general centre would see. Check your laboratory's assay method before adopting the 170 and 410 ng/dL thresholds.

Analysis by Dr Thibaut Benquey