The high rate of false-positive (FP) results in congenital adrenal hyperplasia newborn screening (CAH-NBS) worldwide challenges NBS-programs and reinforces the need of high specificity subsequent tests. Few studies assessed the efficacy of different serum steroids by the available methodologies. Serum 21-deoxycortisol-21DF demonstrated a high diagnostic accuracy in CAH children/adults but was not evaluated in the NBS context. Objective: to evaluate the efficacy of confirmatory tests using different serum steroids by radioimmunossay and liquid chromatography methodologies in the CAH-NBS. Patients:data of 708,437 newborns (NBs) were retrospectively evaluated. Methods: newborns with neonatal-17OHP (N17OHP) results ≥ 2x99.5th percentile were recalled for serum dosages [RIA (17OHP) and LC-MS/MS (17OHP, 21-deoxycortisol-21DF, androstenedione-Δ4, cortisol)]. Hormonal data were validated by CYP21A2 genotyping. Non-parametric tests and ROC-curves were used. Results: the recall rate was 0.045% and, in the serum confirmatory tests, 17OHP remained altered in 26% of newborns by RIA (PPV=30%) and in 11% by LC-MS/MS (PPV=49%); fifty-eight classical NBs were diagnosed and 32 asymptomatic-NBs persisted with increased serum 17OHP levels. In the ROC-curves between false and true-positives, 17OHP/LC-MS/MS had the highest accuracy as a single steroid (cutoff 48.3 ng/ml=100% of sensitivity for classical forms); surprisingly, serum 21DF was not superior than 17OHP/LC-MS/MS. Among the steroid ratios, the [(17OHP+Δ4)/cortisol] presented the highest accuracy (cutoff 24.9 = 100% of PPV to detect salt-wasting form). Conclusions:17OHP and [(17OHP+Δ4)/cortisol] ratio analyzed by LC-MS/MS presented the highest accuracy in the serum NBS tests. Differently that observed in older CAH patients, 21-DF was not superior than 17OHP in newborns as a diagnostic tool to optimize the CAH-NBS.
15 Sep 2022 - 17 Sep 2022