Endocrine Abstracts

JOINT1777

Introduction: Screening of Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency reduces neonatal morbidity and mortality. The quantification of 17-hydroxyprogesterone (17-OHP) using Delayed Fluorescence Immunoassay (DFI) on filter paper blood samples is the standard screening strategy. However, it is associated with a high number of false positives (FP), especially in premature infants. To optimize the positive predictive value (PPV), most screening programs establish cutoff points for 17-OHP based on gestational age (GA). Currently, it is considered more efficient to determine 17-OHP and other adrenal analytes using LC-MS/MS, which may also allow the diagnosis of other types of CAH. In June 2023, CAH screening was implemented in our region.

Objectives: To evaluate the effectiveness of our screening strategy for diagnosing classic CAH. To determine the prevalence and impact of FP by including the measurement of 17-OHP via LC–MS/MS.

Methodology: At 48 hours of life, filter paper samples with 17-OHP values exceeding the 99.95th percentile (p99.95) by DFI are considered positive. Three groups are differentiated based on GA: <33 weeks (weighted p99.95), 33–37 weeks (p99.95 corresponding to the group with the highest gestational age), and >37 weeks (p99.95). All positives are retested using both DFI and LC–MS/MS. The established cutoff points for various adrenal analytes and diagnostic ratios by LC–MS/MS are: 17-OHP>15.1 nmol/l+21-deoxycortisol>2.9 nmol/l or 17-OHP>15.1 nmol/l+ ratio of [17-OHP+Androstenedione]/cortisol>2+ ratio 17-OHP/11-deoxycortisol>10. In neonates <33 weeks and/or <1500 grams, a second filter paper determination by DFI is done at 15 days of life, as done for congenital hypothiroidsm screening. This allows for a single cutoff point in this population. We analyzed the positive cases from the CAH screening (June 1, 2023 – December 31st, 2024). Data were obtained from the neonatal screening program and clinical records.

Results: Out of 21 411 screenings performed, 40 were positive by DFI (55% male). Three out of 40 neonates died early due to other causes. 37 cases were retested, confirming one true positive (a 5-day-old male neonate) by both DFI and LC-MS/MS. Outpatient treatment was started at 7 days of life. In the 36 cases considered false positives (75% from the group 33–37 weeks, 58% male), retesting using LC–MS/MS allowed ruling out classic CAH.

Comments: In the short duration of CAH screening, one male was diagnosed before one week of life. The inclusion of LC–MS/MS in this screening strategy raises the PPV to 100%, avoiding unnecessary interventions in the few false positives.