Congenital Clitoromegaly With Concurrent Congenital Adrenal Hyperplasia and Turner Syndrome: A Case Report

Clitoromegaly in a newborn with otherwise typically appearing female genitalia indicates exposure to excess androgens in fetal life. Congenital Adrenal Hyperplasia (CAH) is the most common cause of virilization at birth and empiric treatment is often pursued due to the risk of life-threatening adrenal crisis. Turner syndrome (TS) does not usually present with atypical genital appearance or other signs of hyperandrogenism, unless Y chromosome material is present. In this report, we describe a newborn who was noted to have clitoromegaly soon after birth with an otherwise normal exam and no syndromic features. Empiric treatment with hydrocortisone and fludrocortisone was started while initial laboratory results were pending. However, prior to receiving CAH hormonal panel results, karyotype testing returned as [45,XO(3)/46,XX(17)], consistent with mosaic TS. Testing for Y chromosome material, pursued as a potential cause of clitoromegaly, was negative. To add to the diagnostic dilemma, newborn screening for CAH was also negative. Results from the CAH panel done soon after birth eventually returned and revealed an elevated 17-hydroxyprogesterone level (17-OHP) of 1540 ng/dl, which is more congruent with non-classical CAH and does not typically result in clitoromegaly at birth. To clarify the diagnosis, a 250 mcg cosyntropin stimulation test was performed after holding steroids for a week. Post-stimulation 17-OHP of 82334 ng/dL confirmed classical CAH secondary to 21-hydroxylase deficiency and genetic analysis identified biallelic pathogenic deletions of CYP21A2 gene. Current TS guidelines recommend testing for Y chromosome material if masculinizing features develop. This case underlines the value of including CAH in the differential diagnosis as another potential cause of virilization in patients with TS. The concurrence of CAH and TS poses added complexity for clinical management due to their overlapping impacts on linear growth, puberty, reproductive function, bone density and metabolic health.