Sustained benefits of growth hormone on body composition, fat utilization,physical strength and agility, and growth in Prader-Willi syndrome are dose-dependent

Background: Obesity and hypotonia in children with Prader-Willi syndrome (P WS) are accompanied by abnormal body composition resembling a growth hormon e (GH) deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. Whil e recent studies have demonstrated short-term benefits of treatment with GH , a critical question is whether beneficial changes persist or wane with pr olonged therapy, and whether these effects on body composition are dose-dep endent as seen in adult GH deficiency. Objectives and Methods: After 24 months of GH theapy at a dose of 1 mg/m(2) /day ("standard dose"), the effects of 12 additional months of GH treatment at varying doses (0.3-1.5 mg/m(2)/day) on growth, body composition, streng th and agility, pulmonary function, resting energy expenditure (REE), and f at utilization were assessed in 46 children with PWS. Percent body fat, lea n muscle mass, and bone mineral density (BMD) were measured by dual X-ray a bsorptiometry (DXA). Indirect calorimetry was used to determine REE and to calculate respiratory quotient (RQ). Results: During months 24-36 of GH therapy, further changes in body composi tion (decrease in fat mass, and increase in lean body mass), growth velocit y, and REE occurred with standard and higher-dose GH therapy (1.5 mg/m(2)/d ay), but not with lower dose GH (0.3 mg/m(2)/day). Prior improvements in BM D, and strength and agility, which occurred during the initial 24 months, w ere sustained during the additional 12 months (to 36 months) regardless of dose. Conclusions: Salutary and sustained GH-induced changes in growth, body comp osition, and physical function in children with PWS require GH doses of >0. 3 mg/m(2)/day. Conversely, BMD increased during the additional 12 months of therapy regardless of GH dose. Lower doses of GH, effective in improving b ody composition in adults with GHD, do not appear to be effective in childr en with PWS.