Sustained benefit after 2 years of growth hormone on body composition, fatutilization, physical strength and agility, and growth in Prader-Willi syndrome

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. Alth ough recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy. Objectives and methods: Effects of 24 months of GH treatment (1 mg/m(2)/d) on growth, body composition, strength and agility, pulmonary function, rest ing energy expenditure, and fat utilization were assessed in 35 children wi th PWS. Percent body fat, lean muscle mass, and bone mineral density were m easured by dual-energy x-ray absorptiometry. indirect calorimetry was used to determine resting energy expenditure and to calculate the respiratory qu otient. Results: Compared with baseline evaluations, increased height velocity (SD score -1.1 +/- 2.5 to 2.2 +/- 2.3; P <.001), reduced percent body fat (46.4 % +/- 8.4% to 40.3% +/- 10.0%, P <.001), and improved respiratory muscle fu nction and physical strength and agility (sit-ups, weight-lifts, running sp eed, and broad lump; P <.01) were observed after 24 months of GH treatment. A decline in respiratory quotient (0.81 +/- 0.07 to 0.75 +/- 0.06; P <.01) and a trend toward increased resting energy expenditure were also observed . Changes in response to GH occurred predominantly during the initial 12 mo nths of GH therapy. Conclusions: Children with PWS had sustained increases in lean body mass, d ecreases in percent body fat, improvements in physical strength and agility , and increased fat oxidation after 24 months of GH therapy, However, betwe en 12 and 24 months, the growth rate slowed. Consequently, encouraging init ial results require even more prolonged study to draw conclusions regarding the long-term value of GH therapy in changing body composition in children with PWS.