Delayed Diagnosis of Congenital Adrenal Hyperplasia Due to 3β-Hydroxysteroid Dehydrogenase Type 2 Deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition associated with enzymatic deficiencies affecting the adrenal steroid synthesis pathway. 21-hydroxylase deficiency (21-OHD), the most common form, is a pathogenic variant of the <i>CYP21A2</i> gene and accounts for >95% of cases. Deficiency of 3β-hydroxysteroid dehydrogenase type 2 (3β-HSD2) is a rare form, accounting for <0.5% of cases. Detection of 3β-HSD deficiency depends on the methods used by laboratories for screening of CAH. We present the case of a 46-year-old female who was diagnosed with 21-OHD CAH at birth. As an adult, she was reviewed in a routine endocrine clinic and showed signs of hyperandrogenism, including hirsutism and male pattern hair loss. She was on prednisolone 3 mg/day and fludrocortisone 200 mcg/day. Trials of multiple antiandrogenic therapies did not help with hirsutism. 17-hydroxyprogesterone concentration was unexpectedly low, despite the low-dose glucocorticoid treatment. This raised our suspicion of an alternative etiology. Further investigations were undertaken, including a 24-hour urinary steroid profile and genetic testing, which led to the diagnosis of 3β-HSD2 deficiency. This case highlights that clinical suspicion of rarer forms of CAH is necessary to identify these cases, as they can lead to delayed diagnosis and treatment and inadequate glucocorticoid replacement.