ODP375 Absence of Virilization With Completely Normal Phenotype in a Newborn Female With Salt-Wasting Classical CAH

Abstract

Background Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that leads to the disruption of adrenal steroidogenesis. 21-hydroxylase deficiency is the most common form and is caused by the mutations in the 21-hydroxylase (CYP21A2) gene. Deficiency in the 21-hydroxylase enzyme can affect aldosterone and cortisol production and shift the pathway to increased androgen production. It is classified as classical and nonclassical depending on the severity of enzyme deficiency. The classical form can present as a life-threatening salt-wasting or a milder form of simple virilizing CAH. Female patients with classical 21-hydroxylase deficiency present with ambiguous genitalia secondary to increased androgen production. We present a case of salt-wasting classical CAH in a female patient with no signs of virilization that was diagnosed based on newborn screening. Case presentation A four-day-old full-term female was referred to our hospital for elevated 17 hydroxyprogesterone (17-OHP) on a newborn screen. She was born via normal vaginal delivery with an uncomplicated prenatal and postnatal course. Her newborn screen was drawn at day 1 of life resulted in 17-OHP of 128.20 nmol/L (normal cutoff of 85 nmol/L). Otherwise, she was active, feeding well with no other concerns. On admission, her vital signs were within normal, with an unremarkable physical examination. Specifically, the genitourinary exam demonstrated normal female external genitalia with no evidence of virilization, no clitoromegaly with a clitoris length of 12 mm and width 1-2 mm, no hyperpigmentation, and with normal-appearing vaginal orifice and urethral meatus. Confirmatory 17-OHP by mass spectrometry was sent along with the metabolic panel, and her initial electrolytes were within normal. Since there was a low suspicion for salt-wasting CAH given her normal labs and unremarkable physical exam, medication was not started, and the patient was admitted for monitoring. The potassium level trended up abnormally to 6.3 mmol/L, which prompted the initiation of empiric treatment with a physiologic dose of Hydrocortisone and Florinef on day of life 7, pending confirmatory 17-OHP level. Confirmatory17-OHP was 1242 ng/dL (normal <78) and following stimulation with Cosyntropin a markedly elevated 17-OHP 27,929.31 ng/dL (normal expected 7-106) and low cortisol level 2 mcg/dL, for which definitive treatment with hydrocortisone and Florinef were initiated. Subsequent genetic testing confirmed the diagnosis of 21-hydroxylase deficiency with mutations in the CYP21A2 gene for I172N, R356W, and c. *13G>A. Further genetic workup to explain the complete lack of virilization, including assessment of an androgen insensitivity panel and whole-exome sequencing, was unremarkable. Conclusion This case illustrates the critical importance of heel-stick newborn screening for CAH to prevent a life-threatening salt-wasting crisis as female patients with classical CAH can present with a phenotypic complete lack of virilization that could be misleading and fatal if not recognized. Presentation: No date and time listed