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Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader–Willi syndrome

Endocrinology and Diabetes Unit, Room K4-212, British Columbia's Children's Hospital, University of British Columbia, 4480 Oak Street, Vancouver, Canada BC V6H 3V4¹ Department of Psychology, British Columbia's Children's Hospital, University of British Columbia, Vancouver, Canada BC V6H 3V4² Department of Metabolic Medicine, Imperial College Faculty of Medicine, Hammersmith Campus, London W12 ONN, UK³ Division of Endocrinology, Alberta Children's Hospital, University of Calgary, Calgary, Canada AB T2T 5C7

(Correspondence should be addressed to J-P Chanoine; Email: jchanoine{at}cw.bc.ca)

Objective: Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader–Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.

Design: A 56-week prospective, randomized, cross-over trial.

Methods: Nine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period.

Results: Eight subjects completed the study. Oct caused a decrease in both acylated (–53%) and desacyl (–54%) fasting ghrelin concentrations (P<0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones.

Conclusions: Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

This article has been cited by other articles:

				A. P. Goldstone, A. J. Holland, B. P. Hauffa, A. C. Hokken-Koelega, M. Tauber, and on behalf of speakers contributors at the Second E Recommendations for the Diagnosis and Management of Prader-Willi Syndrome J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4183 - 4197. [Abstract] [Full Text] [PDF]