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Hyperghrelinemia Precedes Obesity in Prader-Willi Syndrome

Department of Endocrinology, Bone Diseases, Genetics, and Gynaecology (E.F., G.D., F.C.-A., C.M., J.-P.S., M.T.), Centre de Référence du Syndrome de Prader-Willi, Children’s Hospital, Centre Hospitalier Universitaire, and Laboratoire de Biochimie 3 (I.G.), Institut Fédératif de Biologie, Hôpital Purpan, 31059 Toulouse, France; and Institut National de la Santé et de la Recherche Médicale, U563 (F.C.-A., J.-P.S., M.T.) and U558 (C.A., M.T.), University Paul Sabatier, 31403 Toulouse, France

Address all correspondence and requests for reprints to: Professor M. Tauber, Unit of Endocrinology, Hôpital des Enfants, 330 Avenue de Grande Bretagne, TSA 70034, 31059 Toulouse Cedex 9, France. E-mail: tauber.mt{at}chu-toulouse.fr, molinas.c{at}chu-toulouse.fr.

Background: High plasma ghrelin levels have been reported in Prader-Willi syndrome (PWS). However, little is known about plasma ghrelin in these children during the first years of life characterized by a failure to thrive.

Objective: The objective of the study was to investigate total plasma ghrelin levels in children with PWS and controls from 2 months to 17 years.

Subjects and Methods: Forty children with PWS [24 boys, 16 girls, median age 3.6 yr, median body mass index (BMI) Z-score 0.3] were compared with 84 controls (57 boys, 27 girls, median age 4.2 yr median BMI Z-score 0.1). Children were then divided into two groups according to age and GH treatment.

Results: Median plasma ghrelin levels were significantly higher in children with PWS, compared with controls at any age (568 vs. 173, P < 0.0001) and decreased with age in both groups (P < 0.0001). In the whole group of PWS, we found an inverse relationship between ghrelin and BMI Z-score, insulin, homeostasis model assessment insulin resistance index, leptin, and lean mass. Plasma ghrelin levels were higher in children with PWS than controls, both in the youngest children below 3 yr who were not receiving GH (771 vs. 233, P < 0.0001) and in the children older than 3 yr, all of whom were treated with GH (428 vs. 159, P < 0.0001).

Conclusions: Plasma ghrelin levels in children with PWS are elevated at any age, including during the first years of life, thus preceding the development of obesity.