Clinical Features of Classical Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency with Complete Virilisation

Abstract

Background: The most prevalent form of Congenital adrenal hyperplasia (CAH) is 21-hydroxylase deficiency (21-OHD), which accounts for over 90% of CAH cases. This enzymatic defect results in decreased cortisol and aldosterone synthesis, leading to compensatory adrenocorticotropic hormone (ACTH) secretion and consequent adrenal hyperplasia and androgen excess. Objective: The study aimed to describe the clinical, biochemical, radiological, and outcome characteristics of congenital adrenal hyperplasia (CAH) with complete virilisation in a pediatric cohort. Methods: We conducted a retrospective review of nine 46, XX patients presenting with Prader stage IV or V virilisation, followed in the pediatric endocrinology department of Rabat Children’s Hospital over a 10-year period. Clinical presentation, hormonal profile, imaging, genotyping and follow-up were analysed. Results: All patients were diagnosed in the neonatal period. External genitalia were completely virilized (Prader IV–V), with no palpable gonads. Biochemical testing confirmed 21-hydroxylase deficiency in all cases. Salt-wasting crisis occurred in 55% of patients. Karyotyping confirmed 46, XX status. Early genital surgery was performed in six patients. Hydrocortisone and fludrocortisone replacement therapy were initiated. The long-term follow-up showed variable outcomes in terms of growth, bone age advancement, gender identity and surgical results. Conclusion: Complete virilisation in CAH requires early diagnosis and multidisciplinary management to optimise outcome and gender identity support. Delayed diagnosis and inadequate hormone replacement remain key challenges in developing settings.