Hypothalamic and gonadal components of hypogonadism in boys with Prader-Labhart- Willi syndrome.
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.
Eiholzer
Urs
U
Institute Growth Puberty Adolescence, Moehrlistrasse 69, CH-8006 Zurich, Switzerland. mail@childgrowth.org
l'Allemand
Dagmar
D
Rousson
Valentin
V
Schlumpf
Michael
M
Gasser
Theo
T
Girard
Jürg
J
Grüters
Annette
A
Simoni
Manuela
M
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*
D006063:Chorionic Gonadotropin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone