Hypogonadism in boys with Prader-Labhart-Willi syndrome. A specific disorder with hypothalamic and gonadal components.

Context: The specific form of hypogonadism in Prader-Labhart-Willi syndrome (PWS), central or peripheral, remains unexplained.Objectives: The objectives of this study were to investigate the cause of hypogonadism in PWS and determine whether human chorionic gonadotropin (hCG) treatment can restore pubertal development.Design: This was a clinical follow-up study, divided into two samples, over a duration of 1.5 and 4.5 yr.Patients: Eight male infants and six peripubertal boys (age at start of observation, 0.06–0.93 and 8.1–10.8 yr, respectively) with genetically confirmed PWS were studied.Intervention: hCG (500–1500 U twice weekly) was given from age 13.5 yr to the present.Main Outcome Measures: Serum FSH, LH, inhibin B, and testosterone levels and pubertal development were the main outcome measures.Results: Infants with PWS presented normal LH (2.3 ± 0.7 U/liter) and testosterone (2.5 ± 0.9 nmol/liter) levels (mean ± SEM at 5 months) compared with the reference range. However, two thirds of the boys displayed cryptorchidism. Inhibin B levels were at the lowest level of the normal range and decreased significantly between infancy and puberty (at 13 yr, 72 ± 17 pg/ml), whereas FSH secretion increased (9.9 ± 2.6 U/liter). Pubertal maturation stopped at an average bone age of 13.9 yr. hCG therapy increased testosterone (11 ± 2 nmol/liter) and reduced FSH (at 16 yr, 1.1 ± 0.9 U/liter) levels. Testicular volume (5.6 ± 1 ml) and inhibin B (26.5 ± 11.9 pg/ml) remained low.Conclusion: Children with PWS display a specific form of combined hypothalamic (low LH) and peripheral (low inhibin B and high FSH) hypogonadism, suggesting a primary defect in Sertoli and/or germ cell maturation or an early germ cell loss. hCG therapy stimulates testosterone production and virilization.