Dual Heterozygous Mutations in CYP21A2 and CYP11B1 in a Case of Nonclassic Congenital Adrenal Hyperplasia

Background/Objective Nonclassic congenital adrenal hyperplasia (NCCAH) may be overlooked or mistaken for polycystic ovarian syndrome. Unlike congenital adrenal hyperplasia (CAH), the enzymatic activities of 21-hydroxylase or 11β-hydroxylase in NCCAH are not completely lost. In this case, NCCAH presented in a patient with CYP21A2 and CYP11B1 heterozygous mutations, one of which is a variant of unknown significance in CYP11B1 . Case Report A 30-year-old woman presented with a chief complaint of irregular menses and hirsutism. Previous medical history was significant for a prolactin level of 34.7 ng/mL (reference range, 2.0-23.0 ng/mL), a total serum testosterone level of 77 ng/dL (reference range, 25-125 ng/dL, not sex-specific), and a 2-mm × 3-mm pituitary lesion. An adrenocorticotrophic hormone stimulation test increased the 17-hydroxyprogesterone level from 444 ng/dL at baseline to 837 ng/dL at 60 minutes (baseline female reference range and stimulated reference ranges are 10-300 ng/dL and <1000 ng/dL, respectively). Gene sequencing revealed a heterozygous pathogenic CYP21A2 variant and a heterozygous, previously undescribed variant of unknown significance in CYP11B1 . Discussion Unlike CAH, NCCAH presents more subtly and later in life, and salt wasting and hypertension are not typically seen. Although mutations in CYP11B1 that cause steroid 11β-hydroxylase deficiency more commonly lead to the CAH phenotype, cases have been reported of CYP11B1 mutations leading to NCCAH, depending on the location of the mutations. Conclusion This patient's case demonstrates physical examination and laboratory findings suggestive of NCCAH. Our case adds to the database of described mutations in CYP11B1 and suggests that heterozygous mutations in 2 different genes may present phenotypically as NCCAH.