Octreotide Potently Suppresses
Circulating Ghrelin Levels
in Children With Prader-Willi Syndrome
Andrea M. Haqq 1, Diane D. Stadler 2, Ron G.
Rosenfeld 2, Katherine L. Pratt 2, David S. Weigle3,
R. Scott Frayo 3, David E. Cummings 3 , Stephen H.
LaFranchi2, and Jonathan Q. Purnell 2. 1Department
of Pediatrics, Duke University Medical Center, Durham, NC, 27710 USA
Telephone:919-684-5091 Fax: 919-684-8613 2Departments of Pediatrics
and Internal Medicine, Oregon Health & Science University, Portland, OR, United
States and 3Department of Medicine, University of Washington,
Seattle, WA, United States.
Background: Prader-Willi Syndrome (PWS) is a genetic obesity syndrome
characterized in part by growth hormone deficiency and severe hyperphagia and
obesity, beginning in childhood. In contrast to obese children and adults, who
have low ghrelin levels, children with PWS have markedly increased fasting
ghrelin concentrations.
Objective: Since ghrelin increases food intake and body weight in humans
and rodents, the high ghrelin levels might contribute to hyperphagia in PWS.
Treatment with octreotide, a somatostatin agonist, decreases ghrelin in adults
with acromegaly. We therefore sought to determine if octreotide treatment would
decrease fasting ghrelin levels in children with PWS.
Design/Methods: 4 children (2 male, 2 female, mean age 12 years) with PWS
were studied before and after 5-7 days of octreotide treatment (5 mcg/kg/d; SQ
tid). At each visit following an overnight fast, the following parameters were
measured: body weight, resting energy expenditure (REE) by indirect calorimetry,
% body fat by bioelectrical impedance, and plasma ghrelin, leptin and insulin
and serum IGF-1, IGFBP-3 and free IGF-1 levels by radioimmunoassay. In addition,
ghrelin levels were measured at each visit 90 minutes after patients consumed a
standardized breakfast. Food intake and eating behaviors were assessed by
parent-reported 24-hour food intake recalls.
Results: Fasting ghrelin levels in PWS subjects decreased 67% after 5-7
days of octreotide treatment (937  605
vs. 307 248
pg/ml; p<0.05). Postprandial suppression of ghrelin was 24% (p=0.06, pre- vs.
postprandial) before octreotide intervention and 11% (p=0.19) after octreotide
treatment and was seen in all subjects. Body weight, % body fat, REE, energy
intake, leptin, IGF-1, Free IGF-1 and IGFBP-3 did not significantly change
during this brief intervention. However, one parent noted fewer tantrums over
denial of food during the intervention period.
Conclusions: In this pilot study, treatment with octreotide for 5-7 days
markedly decreased fasting ghrelin levels in children with PWS. Children with
PWS also demonstrated postprandial suppression of ghrelin as would be expected
under normal regulatory conditions. Additional controlled studies are needed to
determine if long-term octreotide treatment causes sustained ghrelin suppression
and weight loss in children with PWS.
July 2003
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