21-Deoxycortisol is a Screening Marker for 21-hydroxylase Deficiency

Objective (s): To assess whether 21-deoxycortisol (21deoxy) can be used to predict 21-hydroxylase deficiency (21OHD) in newborns and to evaluate the influence of gestational age and the timing of collection on 21-deoxycortisol concentrations which can impact screening specificity. Study design 17-hydroxyprogesterone (17OHP) and 21-deoxycortisol (21deoxy) were measured in 906 newborn screening specimens (851 unaffected newborns, 55 confirmed cases of 2OHD) to compare their ability to identify babies with 21-hydroxylase deficiency. Additionally, these two steroids were scrutinized in the unaffected cohort to determine the influence of gestational age (ranging from 23-42 weeks) and the timing of the measured concentrations. Results The gestational age of the newborn impacted both 17OHP and 21deoxy concentrations, but the degree of influence was more substantial for 17OHP. Timing of collection, however, did not affect 21deoxy concentrations. Additionally, 21deoxy was a better predictor of 21OHD status than 17OHP, with little overlap in concentrations between the unaffected population and confirmed cases of 21OHD. A streamlined decision tree using solely 21deoxy (cutoff values of 0.85 ng/ml), yielded a 91.7% positive predictive value for 21OHD screening. Conclusions Our findings demonstrate that 21deoxy is a key disease marker of 21OHD and could be used to improve the accuracy of newborn screening for this disorder.