The diagnostic value of stimulated androgen ratios in 5-alpha reductase type 2 (SRD5A2) deficiency: a case series and review of the literature.

OBJECTIVES

Precise and timely diagnosis is essential in the management of children born with atypical genitalia/differences or disorders of sex development (DSD) to provide optimal personalised care. Establishing the diagnosis can be challenging and time-consuming. The human chorionic gonadotrophin (hCG) stimulation test is useful in assessing male gonadal function, and stimulated testosterone: 5α-dihydrotestosterone (T:DHT)>10 suggests 5-alpha reductase type 2 (SRD5A2) deficiency.

METHODS

We report the clinical, hormonal and genetic data of patients with 46, XY DSD with genetically confirmed SRD5A2 deficiency to assess the value of the hCG-stimulated T:DHT ratio in the diagnostic work-up. Additionally, we reviewed the literature on the usefulness of hCG-stimulated androgen ratios in determining DSD aetiology.

RESULTS

Of 14 patients with genetically confirmed SRD5A2 deficiency, including one novel variant, nine underwent hCG stimulation test: seven in infancy, one at 4 years and one at puberty. A T:DHT ratio above 10 was observed in seven patients (median: 15; range: 10.7-66.5). Two patients, aged one month and 4 years, had ratios of 8.3 and 4.4, respectively. Urinary steroid profiling (GC/MS) suggested SRD5A2 deficiency in all patients who had the testing (n=13). No association was found between T:DHT ratios and age at presentation or external masculinisation score (EMS).

CONCLUSIONS

The hCG stimulation test appears less sensitive than urinary steroid profiling in establishing the diagnosis of SRD5A2 deficiency.