The following is a summary of “High Relevance of 21-Deoxycortisol, (Androstenedione + 17α-Hydroxyprogesterone)/Cortisol, and 11-Deoxycortisol/17α-Hydroxyprogesterone for Newborn Screening of 21-Hydroxylase Deficiency,” published in the December 2022 issue of Endocrinology & Metabolism by Watanabe, et al.

The comprehensive analysis of steroid profiles for developing algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) had received very little attention in the literature. For a study, researchers sought to build an algorithm for LC-MS/MS measurement of 2,077 dried blood spot samples in Tokyo in order to screen newborns for 21OHD.

The panel of LC-MS/MS included five steroids: (17α-hydroxyprogesterone [17αOHP], 21-deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]). A total of 63 “screening positive” neonates who were referred to an endocrinologist from Cohort A (n = 26 with 21OHD; n = 37 false-positive; obtained from 2015 to 2020) and Cohort B (n = 2014) with 17αOHP values in the 97th percentile or above from the first-tier test with 17αOHP ELISA from 2020 to 2021 were assayed.

When Cohort A was analyzed, it was discovered that the three indices 21DOF, 11DOF/17αOHP, and (4AD + 17αOHP)/F had a higher area under the curve (AUC) values (0.999, 0.997, 0.989, respectively), whereas the 17αOHP AUC was lower. As a result, the 3 markers were added to the 17αOHP to define the screening method. Following Cohort B’s analysis, it was discovered that the new method provided 92% of anticipated positive predictive value without false-negative situations. They also established reference values for the five steroids at 4–7 days after delivery, according to sex and gestational age (GA), and found that levels of 21DOF were incredibly low at any GA, regardless of sex differences.

The investigation showed the high significance of 21DOF, (4AD + 17αOHP)/F, and 11DOF/17αOHP for 21OHD screening as opposed to 17αOHP.