Establishing the Cut-Off Values of 17-Hydroxyprogesterone for Diagnosing Congenital Adrenal Hyperplasia: A Prospective Observational Study in a Tertiary Care Hospital.

Introduction Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder primarily caused by 21-hydroxylase enzyme deficiency, impairing cortisol synthesis and resulting in elevated androgen levels. CAH presents in two classical forms: salt-wasting (SW) and simple virilizing (SV). Although CAH is rare in India, regional variations and the absence of a national newborn screening (NBS) program pose significant challenges to accurate diagnosis. This study aimed to assess the incidence of CAH in a regional population and evaluate 17-hydroxyprogesterone (17-OHP) cut-off levels for effective screening. Methods This prospective observational study was conducted at a tertiary care hospital in Pune, India, over 18 months (July 2022 to March 2024). Newborns at term with elevated 17-OHP levels in initial screenings were included, while those whose mothers had chronic steroid use were excluded. Heel prick blood samples were collected between 72 and 96 hours postbirth and analyzed using enzyme-linked immunosorbent assay (ELISA). Infants with borderline or elevated initial results underwent a second screening at six weeks, followed by confirmatory testing for adrenocorticotropic hormone (ACTH) and cortisol levels. Results Out of 3,607 newborns screened, 638 had elevated 17-OHP levels and were enrolled in the study. The follow-up rate was 36.68%, with 234 infants completing the second screening. Only one infant was diagnosed with CAH, yielding an incidence rate of 1:3,607. This infant presented hyperpigmentation but no atypical genitalia or other classical symptoms of CAH. Conclusions The study estimated the incidence of CAH at one in 3,607 live births in our study done in western Maharashtra, India. The findings emphasize the importance of region-specific 17-OHP cut-off values for improving screening accuracy. Establishing a national NBS program is crucial for early detection and timely intervention.