Peptides associated with hyperphagia in adults with Prader-Willi syndrome before and during GH treatment

Growth Horm IGF Res. 2003 Dec;13(6):322-7. doi: 10.1016/s1096-6374(03)00077-7.


Prader-Willi syndrome (PWS) is a complex genetic disorder characterised by mild mental retardation and distinct physical, behavioural, and psychiatric features. One of the cardinal symptoms is excessive eating, which--if left untreated--leads to extreme obesity. In the present study we have examined circulating levels of peptides with documented association to hyperphagia in young adults with PWS. Since growth hormone (GH) is often used nowadays to correct GH insufficiency during childhood PWS, we also studied the impact of GH administration on the peptides. Seventeen adults, 9 men and 8 women, 17-32 years of age with a mean BMI of 35+/-3.2 kg/m(2) participated. All had clinical PWS (Holm's criteria). Genetic testing was performed in all patients and in 11 the diagnosis was confirmed. They were randomized to treatment with either placebo or GH (Genotropin, Pharmacia Corporation) for 6 months. Subsequently all received open label treatment to provide all subjects with 12 months active GH treatment. Doses were individually titrated. Weight, BMI, oxytocin (baseline only), leptin, Neuropeptide Y (NPY), and ghrelin were evaluated at baseline and after 6 and 12 months. At baseline plasma mean oxytocin was within and serum ghrelin just above the normal range (14.7+/-1.2 pmol/L and 0.87+/-0.12 microg/L, respectively). Serum leptin levels were high above and plasma NPY levels within the lower normal range (47.8+/-29.1 microg/L and 13+/-1 pmol/L, respectively). Results were independent of genotype. No changes in mean BMI, ghrelin, leptin or NPY were seen following GH treatment.

Conclusion: Leptin levels were in general high reflecting obesity and as a consequence NPY levels were low. In simple obesity oxytocin levels are high, while ghrelin levels are suppressed. In view of the adiposity oxytocin circulated in abnormally low and ghrelin in abnormally high concentrations in our patients. GH treatment of PWS patients did not change ghrelin, leptin or NPY. We suggest that both oxytocin and ghrelin are involved in the pathogenesis of hyperphagia seen in PWS.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Body Mass Index
  • Eating / physiology
  • Fasting / blood
  • Female
  • Ghrelin
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Hyperphagia / blood
  • Hyperphagia / drug therapy
  • Hyperphagia / etiology*
  • Leptin / blood*
  • Male
  • Neuropeptide Y / blood*
  • Obesity / blood
  • Obesity / drug therapy
  • Obesity / etiology
  • Oxytocin / blood*
  • Peptide Hormones / blood*
  • Prader-Willi Syndrome / complications*
  • Prader-Willi Syndrome / drug therapy


  • Ghrelin
  • Leptin
  • Neuropeptide Y
  • Peptide Hormones
  • Human Growth Hormone
  • Oxytocin