Background: Leydig Cell Hypoplasia (LCH) is a very rare autosomal recessive condition that is manifested by a wide spectrum of phenotypes, ranging from completely female external genitalia to male genitalia. Long-term outcome in these patients is unclear.
Objectives: To assess sex assignment, clinical characteristics and long-term outcome of 46,XY LCH cases.
Patients and Methods: Through the I-DSD registry and its users, clinical information on first and last presentation was gathered on 17 cases of 46,XY LCH born before 2004. A questionnaire was sent to each clinician at these centres to collect information on long-term health. The diagnosis was reached through clinical biochemistry in all and confirmed by genetics in 13 cases.
Results: The median age at the time of first presentation and last assessment was 17 years (range 8 days, 45 years) and 22.8 years (7.7, 62), respectively. Current gender was male in 4 (23%) and female in 13 (77%); two cases were reassigned, one from female to male at 5.3 years and the other from male to female at 17 years. Median EMS, out of 12, at first presentation was 5 (5, 6) and 2 (1, 5) in cases raised as male and female, respectively. All cases had surgery: median age at last repair of hypospadias in males was 5.8 years (2, 8.4); median age at bilateral gonadectomy in the females was 17.9 years (2.2, 46). Cases raised as males were likely to experience more surgical interventions with a median number of hypospadias repairs of 2 (1-4). At last presentation, undermasculinisation was observed in all 4 males with median EMS of 9 (6-9); all of them had micropenis, 2 (50%) had delayed puberty and one also had low testicular volume and hypospadias. All male cases had low testosterone levels despite elevated gonadotrophins. Among the 13 females, 11 (85%) required oestrogens to induce secondary sex characteristics. Of the 17 cases, DXA was performed in 8 (47%) and 7 (88%) of these cases exhibited osteopenia/osteoporosis. One male had azoospermia and 2 obese females developed metabolic syndrome.
Conclusion: Children with LCH can present with a variable level of undermasculinisation and are more likely to be raised as females. However, irrespective of the sex assignment, there is ongoing evidence of hypogonadism and co-morbidities in young adulthood. A standardised approach to management and monitoring clinical outcomes is required.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology