Endocrine Abstracts

Case history: A 14.5-year-old girl was brought forward by her mother to the paediatric endocrine clinic in view of virilised genitalia, absent breast development and primary amenorrhoea. Her genital appearance had changed gradually throughout childhood though she never disclosed this to her parents. She was otherwise healthy with no significant family history of note. On examination, she had fused labioscrotal folds containing 10–12 ml testis. There was no obvious vaginal dimple and she had a 7 cm clitoral-penile structure with hypospadias, stage 4 pubic hair and stage 2 breast development. At 17 she was referred to UCLH adult DSD service for gonadectomy.

Investigations: Tests included an endocrine profile, synacthen test, 3-day human chorionic gonadotropin (HCG) test, a urine steroid profile and pelvic ultrasound. Genetic tests included a karyotype and testing for disorders of sexual development (DSD) mutations.

Results and treatment: Bloods showed the following: AMH of 24.7 pmol/l (females 3.0–46.6; males 9.4–331.8), inhibin B 65 ng/l (females <341; males 25–325), DHEAS 6.76 umol/l (females 1.2–6.7; males 2.8–10.0), 17-hydroxyprogesterone 2.8 nmol/l (0.3–6.3), testosterone 8.5 nmol/l, oestradiol 51 pmol/l, LH 2.8 IU/l and FSH 10.4 IU/l. TFTs, synacthen test, 3-day HCG test and urinary steroid profile were normal. Karyotype was 46XY. A variant mutation of NR5A1 gene was found. No Mullerian structures were observed on pelvic ultrasound and testes were present in the labioscrotal folds bilaterally. She was referred to a clinical psychologist and following prolonged consultations opted for feminising therapy after given the options of masculinising/feminising surgery or let nature take its course. She was started on a gonadotropin-releasing hormone agonist and later started on oestradiol valerate 1 mg, which was eventually increased to 2 mg in view of fatigue. She is due to have gonadectomy later on this year with examination under anaesthesia and cystoscopy. Subsequent surgeries will involve clitoral reduction and vaginoplasty.

Conclusion and points for discussion: Virilisation at puberty is a feature of several forms of 46XYDSD of which NR5A1 mutations are a relatively recently recognised subtype. This is a difficult clinical scenario as the natural history of gender identity is not well described as individuals grow older. Gamete preservation in DSD is often not routinely offered but is likely to become an important part of management. It is important not to rush with irreversible gender assigning medical and surgical therapy. Hormonal blocking therapy may be the most appropriate treatment until the patient has received prolonged psychological therapy and is more mature to decide regarding gender assigning treatment.