Endocrine Abstracts

Background: 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency is an exceptionally rare (<1 in 1,000,000) form of congenital adrenal hyperplasia (CAH), caused by pathogenic variants in HSD3 B2. It disrupts adrenal and gonadal steroidogenesis, leading to impaired cortisol and aldosterone synthesis and accumulation of steroid precursors. Clinical presentation in 46, XY infants includes ambiguous genitalia, hypospadias, and cryptorchidism, with or without salt-wasting crises. Diagnosis requires comprehensive hormonal profiling, ideally during ACTH stimulation, demonstrating elevated 17-hydroxypregnenolone, pregnenolone, and DHEA with relatively low 17-OHP, androstenedione, and cortisol). Genetic confirmation is recommended by Endocrine Society guidelines. Lifelong endocrine follow-up is essential to reduce morbidity, prevent adrenal crises, and monitor for testicular adrenal rest tumours (TARTs), a recognised complication that may mimic malignancy.

Case: We describe a male patient with neonatal presentation (ambiguous genitalia, cryptorchidism, hypospadias) and urinary steroid profiling consistent with 3β-HSD deficiency, who had no long-term endocrine follow-up. He re-presented in adulthood with infertility and primary hypogonadism. Bilateral hyper vascular testicular lesions were detected on ultrasound, raising suspicion of malignancy. Past history included an ITU admission with sepsis in 2015, consistent with unrecognised adrenal crisis. On initiation of oral dexamethasone (0.5 mg nocte), follow-up ultrasound demonstrated reduction in lesion size, strongly suggesting TARTs. Fertility evaluation is ongoing including genetic testing for partner screening.

Discussion: This case illustrates the consequences of untreated 3β-HSD deficiency extending into adulthood. Endocrine Society and UK guidance highlight the importance of accurate biochemical diagnosis, genetic confirmation, and structured transition to adult services. In males with CAH, periodic testicular ultrasound is recommended to screen for TARTs. Differentiating TARTs from testicular cancer is critical; regression with glucocorticoid therapy supports the diagnosis of TARTs and can prevent unnecessary orchidectomy. Early and adequate hormone replacement is vital not only to prevent adrenal crisis but also to improve fertility potential by reducing intratesticular mass effect. This case reinforces that CAH variants other than 21-hydroxylase deficiency require the same principles of lifelong multidisciplinary endocrine care, including reproductive and genetic counselling.

Conclusion: Untreated 3β-HSD deficiency is extremely rare in adulthood. Recognition of this condition, adherence to guideline-based diagnostic pathways, and appropriate long-term management are essential. Glucocorticoid therapy can induce regression of TARTs, avoid unnecessary surgery, and optimise fertility prospects. This case underscores the importance of ongoing surveillance and tailored endocrine care for all CAH variants.