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.
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.


METHODS
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.
De Waele
Kathleen
K
Endocrinology and Diabetes Unit, British Columbia's Children's Hospital, University of British Columbia, 4480 Oak Street, Vancouver, Canada.
Ishkanian
Stacey L
SL
Bogarin
Roberto
R
Miranda
Charmaine A
CA
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
Pacaud
Danièle
D
Chanoine
Jean-Pierre
JP
D000293:Adolescent; D001066:Appetite / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D002648:Child; D018592:Cross-Over Studies; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005705:Gallbladder Diseases / Q000000981:diagnostic imaging; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D054439:Ghrelin / Q000097:blood*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D015282:Octreotide / Q000008:administration & dosage*; D019894:Peptide YY / Q000097:blood; D011218:Prader-Willi Syndrome / Q000188:drug therapy* / Q000378:metabolism; D014463:Ultrasonography
D001786:Blood Glucose; D005765:Gastrointestinal Agents; D054439:Ghrelin; D019894:Peptide YY; D007334:Insulin-Like Growth Factor I; D015282:Octreotide