title: Increased adrenal androgen levels in patients with Prader-Willi syndrome are associated with insulin, IGF-I, and leptin, but not with measures of obesity.
abstract: OBJECTIVE
  Since hyperandrogenism in simple obesity is assumed to arise from hyperinsulinism and/or increased insulin-like growth factor I (IGF-I) or leptin levels, we examined how in patients with Prader-Willi syndrome (PWS), the most frequent form of syndromal obesity, the accelerated adrenarche can be explained despite hypothalamic-pituitary insufficiency with low levels of insulin and IGF-I.
  
  
  METHODS
  In 23 children with PWS and a mean age of 5.6 years, height, weight, fat mass, fasting insulin concentration, insulin resistance (by HOMA-R; see text), and leptin and IGF-I levels were determined to test whether they explain the variance of the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), of androstenedione, and of cortisol before and during 42 months of therapy with growth hormone.
  
  
  RESULTS
  The baseline DHEAS, DHEA, and androstenedione concentrations were increased as compared with age-related reference values, whereas the cortisol level was always normal. During growth hormone treatment, the DHEA concentration further rose, and the cortisol level decreased significantly. The insulin and IGF-I concentrations were low before therapy, while fat mass and leptin level were elevated. The hormonal covariates provided alone or together between 24 and 60% of the explanation for the variance of adrenal androgen levels, but the anthropometric variables did not correlate with them.
  
  
  CONCLUSIONS
  In children with PWS, elevated androgen levels correlate with hormones that are usually associated with adiposity. However, the lack of direct correlations between disturbed body composition and androgen levels as well as the increased sensitivity to insulin and IGF-I are abnormalities specific to PWS, potentially caused by the underlying hypothalamic defect.
authors.affiliation: Foundation Growth Puberty Adolescence, Zürich, Switzerland.
authors.forename: Dagmar
authors.initials: D
authors.lastname: L'Allemand
authors.forename: Urs
authors.initials: U
authors.lastname: Eiholzer
authors.forename: Valentin
authors.initials: V
authors.lastname: Rousson
authors.forename: Jürg
authors.initials: J
authors.lastname: Girard
authors.forename: Werner
authors.initials: W
authors.lastname: Blum
authors.forename: Toni
authors.initials: T
authors.lastname: Torresani
authors.forename: Theo
authors.initials: T
authors.lastname: Gasser
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000378:metabolism*; D000704:Analysis of Variance; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D000886:Anthropometry; D001823:Body Composition; D002648:Child; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000378:metabolism*; D011218:Prader-Willi Syndrome / Q000378:metabolism* / Q000628:therapy; D011446:Prospective Studies; D011629:Puberty, Precocious / Q000378:metabolism
chemical_list: D000728:Androgens; D007328:Insulin; D020738:Leptin; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone