Endocrine Abstracts

JOINT3732

Background: 11-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia (CAH) caused by mutations in the CYP11B1 gene. This mutation disrupts cortisol synthesis, leading to overproduction of ACTH. Elevated ACTH results in excessive deoxycorticosterone (DOC), a weak mineralocorticoid, causing hypernatremia, hypertension, and hypokalemia. Female patients may exhibit virilization at birth, while male patients are often diagnosed later with premature puberty and hypertension. This case report describes a novel mutation in the CYP11B1 gene identified in a patient presenting with vaginal stenosis and premature pubarche.

Case presentation: A 6-year-old girl was referred to the endocrinology clinic at 4 months of age due to ambiguous genitalia. Physical examination revealed normal blood pressure and no hyperpigmentation. Genital examination corresponded to Prader Stage 3; karyotyping confirmed a 46, XX profile. Neonatal screening indicated elevated 17-hydroxyprogesterone levels, leading to an initial diagnosis of 21-hydroxylase deficiency. Hydrocortisone therapy was initiated, and vaginal repair was performed under stress dosing. However, genetic testing for 21-hydroxylase was negative, prompting discontinuation of the medication. At 3 years and 9 months, signs of androgen excess emerged, including acne and Tanner Stage B1P3 pubic hair development, with an advanced bone age of 7.5 years. Laboratory analysis showed LH at 0.11 mIU/ml and FSH at 0.8 mIU/ml, inconsistent with central precocious puberty, and a 17-OHP level of 4.71 ng/ml. Whole exome sequencing revealed a mutation in the CYP11B1 gene: chr8:143960454A>G, c.389T>C (p.Phe130Ser). Both parents were carriers, confirming the diagnosis of 11β-hydroxylase deficiency. Currently, at 6 years old, she is receiving hydrocortisone treatment (10 mg/m²). Her bone age is now 8 years, with normal growth velocity and cessation of signs of androgen excess, maintaining a prepubertal state.

Conclusion: The CYP11B1 gene is associated with over 100 mutations, including missense/nonsense mutations, splicing errors, and various deletions and insertions. This report highlights a patient with CAH due to a novel CYP11B1 mutation, resulting in reduced enzyme activity and androgen excess, leading to clinical manifestations such as virilization and hormonal imbalances. Hormone replacement therapy is essential, but achieving the right balance can be challenging.