Hyperghrelinemia is a common feature of Prader-Willi syndrome and pituitary stalk interruption: a pathophysiological hypothesis.
BACKGROUND
Elevated plasma ghrelin levels have recently been reported in adults and children with Prader-Willi syndrome (PWS). The aim of the study is to investigate the relationship between obesity, growth hormone (GH) deficiency (GHD) and ghrelinemia in PWS and to examine whether hyperghrelinemia is specific to PWS.


METHODS
We measured fasting ghrelinemia in children with PWS, idiopathic GHD (iGHD), obese children, controls and in 6 children presenting another congenital syndrome associated with GHD: pituitary stalk interruption (PSI).


RESULTS
Children with PWS exhibited significantly higher ghrelin levels (995 pg/ml (801/1,099, median 1st/3rd quartile)) than iGHD (517 pg/ml (392/775)), obese (396 pg/ml (145/610)) and control (605 ng/ml (413/753)) children. Similar to PWS hyperghrelinemia was found in PSI children (1,029 pg/ml (705/1,151)), and was not modified by GH treatment.


CONCLUSIONS
We conclude that hyperghrelinemia in PWS and PSI is not related to GH secretion. We hypothesize that a major site of ghrelin action is at the hypothalamic level and that a 'ghrelin resistance' syndrome may be present in these patients, primarily due to a hypothalamic defect. Combined alterations such as impaired serotonin receptor regulation associated with abnormal ghrelin responsiveness are probably responsible for obesity in PWS.
Tauber
Maithé
M
Division of Endocrinology, Bone Diseases, Genetics and Gynecology, Children's Hospital, INSERM U563 (CPTP), IFR 30, Hôpital Purpan, Toulouse, France. crc@chu-toulouse.fr
Conte Auriol
Françoise
F
Moulin
Pierre
P
Molinas
Catherine
C
Delagnes
Véronique
V
Salles
Jean Pierre
JP
D000375:Aging / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D000013:Congenital Abnormalities / Q000097:blood; D005260:Female; D054439:Ghrelin; D013006:Growth Hormone / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D009765:Obesity / Q000097:blood; D036361:Peptide Hormones / Q000097:blood*; D010902:Pituitary Gland / Q000002:abnormalities*; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D043202:Steroid Metabolism, Inborn Errors / Q000097:blood
D054439:Ghrelin; D036361:Peptide Hormones; D019382:Human Growth Hormone; D013006:Growth Hormone