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Circulating Ghrelin Levels Are Suppressed by Meals and Octreotide Therapy in Children with Prader-Willi Syndrome

Division of Endocrinology (A.M.H., R.G.R., K.L.P., S.H.L.), Department of Pediatrics; and Division of Endocrinology, Diabetes, and Clinical Nutrition (D.D.S., J.Q.P.), Department of Medicine, Oregon Health & Science University, Portland, Oregon 97201; and Division of Metabolism, Endocrinology, and Nutrition (D.S.W., R.S.F., D.E.C.), Department of Medicine, University of Washington, Seattle, Washington 98108

Address correspondence and requests for reprints to: Andrea M. Haqq, M.D., Duke University Medical Center, Department of Pediatrics, Division of Endocrinology and Diabetes, 306FA Bell Building, Box 3080, Durham, North Carolina 27710. E-mail: haqq0001{at}mc.duke.edu.

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 µg/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.

This study was conducted through the Oregon Health & Science University General Clinical Research Center (M01-RR-00334) and by National Institutes of Health Grants K-23-DK-02689 (to J.Q.P.) and DK02860 (to D.S.W.).

Abbreviations: Agrp, Agouti-related protein; BMI, body mass index; CV, coefficient(s) of variation; IGFBP, IGF binding protein; IRMA, immunoradiometric assay; LM, lean mass; NPY, neuropeptide Y; PWS, Prader-Willi syndrome; REE, resting energy expenditure.

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