Context: Fasting levels of plasma ghrelins are grossly elevated in children with Prader-Willi syndrome (PWS). The cause of this elevation and the regulation of ghrelins in PWS is largely unknown. The regulatory role of individual nutritional components and of growth hormone (GH) is not well characterised.

Objective: We investigated the influence of GH on acylated (aGhr) and total ghrelin (tGhr) concentrations before and after an oral glucose load, and on insulin resistance in PWS children.

Design, Patients and Interventions: In a clinical follow-up study, plasma ghrelins were measured during an oral glucose tolerance test, and parameters of insulin resistance were determined in 28 PWS children before and/or 1.18 (0.42 - 9.6) years (median, range) after start of GH therapy (0.035 mg/kg body weight/d).

Main Outcome Measures: Fasting and post glucose concentrations of aGhr and tGhr, and HOMA2 insulin resistance were the main outcome measures.

Setting: The study was conducted in a single center (University Children's Hospital).

Results: High fasting (1060 ± 292 [SD] pg/ml; n = 12) and post glucose trough (801 ± 303 pg/ml; n = 10) tGhr concentrations in GH-untreated PWS children were found to be decreased in the GH treated group (fasting 761 ± 247 pg/ml, n = 24, P = 0.006; post glucose 500 ± 176 pg/ml, n = 20; P = 0.006). In contrast, aGhr concentrations and insulin resistance were not changed by GH treatment. Both aGhr and tGhr concentrations were decreased by oral carbohydrate administration, independent of the GH treatment status.

Conclusions: Our results indicate that in PWS children aGhr and tGhr are differentially regulated by GH.