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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-08-0462v1 159/4/381    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by De Waele, K. Articles by Chanoine, J. P. PubMed PubMed Citation Articles by De Waele, K. Articles by Chanoine, J. P.

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

K De Waele, Endocrinology and Diabetes Clinic K4-212, British Columbia Childrens Hospital, Vancouver, British Columbia, Canada
S Ishkanian, Endocrinology and Diabetes Clinic K4-212, British Columbia Childrens Hospital, Vancouver, British Columbia, Canada
R Bogarin, Endocrinology and Diabetes Clinic K4-212, British Columbia Childrens Hospital, Vancouver, British Columbia, Canada
C Miranda, Psychology, British Columbia Childrens Hospital, Vancouver, British Columbia, Canada
M Ghatei, Medicine, Imperial College London, London, United Kingdom
S Bloom, Div of Endocrinology and Metabolism, Royal Postgrad Med School/ Hammersmith Hospital, London, United Kingdom
D Pacaud, Pediatrics, Alberta Children's Hospital, Calgary, Alberta, Canada
J Chanoine, Endocrinology and Diabetes Clinic K4-212, British Columbia Childrens Hospital , Vancouver, British Columbia, V6H 3V4, Canada

Correspondence: Jean Pierre Chanoine, Email: jchanoine{at}cw.bc.ca

Abstract

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: 56-week prospective, randomized, cross-over trial

Methods: Nine subjects with PWS (age 14.6 [10.8-18.9] yrs, BMI z-score +2.0 [0.6-3.0], mean [95% CI]) received either Oct (30 mg) or saline IM every 4 weeks for 16 weeks and were switched over to the other treatment after a 24 week wash out 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 PYY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in IGF-1 concentrations, an increase in HbA1c and transient elevation of blood glucose in 2 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 of ghrelin receptor activity that do not interfere with other appetite-regulating peptides.