7634 Delayed Diagnosis of Classical Congenital Adrenal Hyperplasia: Case Series and Literature Review

Abstract Disclosure: B. Jafar: None. M. Kilberg: None. M.G. Vogiatzi: Other; Self; Consultant for Spruce, Crinetics and Eton. Research support from Neurocrine, Spruce and Adrenas. Congenital adrenal hyperplasia affects (CAH) 1 in 15,000 newborns and is the most common adrenal insufficiency. Newborn screening (NBS) for CAH began with the development of a radioimmunoassay, measuring 17 α-hydroxyprogesterone (17OHP) using blood on microfilter paper. 17OHP screening due 21-hydroxylase deficiency is now part of the NBS in many countries. Although this has revolutionized CAH diagnosis for both simple virilizing (SV) and salt wasting (SW) CAH, NBS was developed to prevent salt wasting crises, especially in 46,XY CAH where neonates may be otherwise asymptomatic. Additional pitfalls to testing include improper sampling, steroid use perinatally and postnatally and a sex driven discrepancy. We present 7 cases of CAH who presented later in life, all with a normal NBS. Patient A presented as a 2-week-old 46,XX presenting with clitoromegaly. NBS 17OHP was 14.7ng/mL (normal <30ng/mL), serum testing was concordant with 17OHP 221 ng/dL (normal 1-5-day infant = <460ng/dL), and pelvic ultrasound showed a uterus. High dose ACTH stimulation testing was ultimately obtained at 7 months of life, showing adrenal insufficiency with a cortisol peak of 6 mcg/dL. 17OHP baseline was 6,632 ng/dL and peaked at 24,115 ng/dL.Patients B, C and D were 46,XY, presenting between ages 4-8 YO with advanced bone age (BA) and premature adrenarche. Their laboratory evaluations showcased elevated 17OHP, low peak in cortisol level.Patients E, F and G were 46,XY, presenting between ages 3-6 YO with central precocious puberty, and advanced BA. Their laboratory evaluations showcased elevated 17OHP, pubertal gonadotropins and low peak in cortisol level.All patients were initiated on hydrocortisone replacement given the diagnosis of SV CAH and associated adrenal insufficiency. 3 patients elected to pursue treatment for central precocious puberty. 2 patients were started on an aromatase inhibitor for advanced BA.Of the 7 cases we present, all were simple virilizing. While the goal of the NBS (preventing salt wasting crises) may have been satisfied, it is plausible that these patients may have been remained undiagnosed entirely due to reports of normal screening tests. These cases highlight the importance for providers to pursue the diagnosis of classical CAH in spite of normal screening - detecting CAH and initiating hydrocortisone therapy prior to adrenal crisis is imperative while the other noted impacts of growth and puberty deserve discussions of management options, education and counseling for future implications. Presentation: 6/3/2024