title: Hypothalamic and gonadal components of hypogonadism in boys with Prader-Labhart- Willi syndrome.
abstract: BACKGROUND
  The specific form of hypogonadism in Prader-Labhart-Willi syndrome (PWS), central or peripheral, remains unexplained.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  This was a clinical follow-up study, divided into two samples, over a duration of 1.5 and 4.5 yr.
  
  
  METHODS
  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.
  
  
  METHODS
  hCG (500-1500 U twice weekly) was given from age 13.5 yr to the present.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute Growth Puberty Adolescence, Moehrlistrasse 69, CH-8006 Zurich, Switzerland. mail@childgrowth.org
authors.forename: Urs
authors.initials: U
authors.lastname: Eiholzer
authors.forename: Dagmar
authors.initials: D
authors.lastname: l'Allemand
authors.forename: Valentin
authors.initials: V
authors.lastname: Rousson
authors.forename: Michael
authors.initials: M
authors.lastname: Schlumpf
authors.forename: Theo
authors.initials: T
authors.lastname: Gasser
authors.forename: Jürg
authors.initials: J
authors.lastname: Girard
authors.forename: Annette
authors.initials: A
authors.lastname: Grüters
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
mesh_terms: D002648:Child; D002675:Child, Preschool; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy / Q000209:etiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011218:Prader-Willi Syndrome / Q000503:physiopathology*; D011627:Puberty / Q000187:drug effects / Q000502:physiology*
chemical_list: D006063:Chorionic Gonadotropin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone