Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome.
Prader-Willi syndrome (PWS) is characterized by severe obesity, hyperphagia, hypogonadism, and GH deficiency. Unlike individuals with common obesity, who have low fasting-plasma ghrelin concentrations, those with PWS have high fasting-ghrelin concentrations that might contribute to their hyperphagia. Treatment with octreotide, a somatostatin agonist, decreases ghrelin concentrations in healthy and acromegalic adults and induces weight loss in children with hypothalamic obesity. This pilot study was performed to determine whether octreotide administration (5 microg/kg.d) for 5-7 d lowers ghrelin concentrations and affects body composition, resting energy expenditure, and GH markers in children with PWS. Octreotide treatment decreased mean fasting plasma ghrelin concentration by 67% (P < 0.05). Meal-related ghrelin suppression (-35%; P < 0.001) was still present after intervention but was blunted (-11%; P = 0.19). Body weight, body composition, leptin, insulin, resting energy expenditure, and GH parameters did not change. However, one subject's parent noted fewer tantrums over denial of food during octreotide intervention. In conclusion, short-term octreotide treatment markedly decreased fasting ghrelin concentrations in children with PWS but did not fully ablate the normal meal-related suppression of ghrelin. Further investigation is warranted to determine whether long-term octreotide treatment causes sustained ghrelin suppression, changes eating behavior, and induces weight loss in this population.
Haqq
Andrea M
AM
Division of Endocrinology, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon 97201, USA. haqq0001@mc.duke.edu
Stadler
Diane D
DD
Rosenfeld
Ron G
RG
Pratt
Katherine L
KL
Weigle
David S
DS
Frayo
R Scott
RS
LaFranchi
Stephen H
SH
Cummings
David E
DE
Purnell
Jonathan Q
JQ
D001519:Behavior / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002648:Child; D005260:Female; D005502:Food; D054439:Ghrelin; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D006963:Hyperphagia / Q000209:etiology; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000178:diet therapy / Q000209:etiology / Q000628:therapy; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use*; D036361:Peptide Hormones / Q000097:blood*; D010865:Pilot Projects; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology
D054439:Ghrelin; D006728:Hormones; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D020738:Leptin; D036361:Peptide Hormones; D007334:Insulin-Like Growth Factor I; D015282:Octreotide