Context: GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies.
Objectives: Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults.
Design: We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods.
Setting: The study was conducted at outpatient treatment facilities at four U.S. academic medical centers.
Patients: Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations.
Intervention: Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated.
Main outcomes measures: Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry.
Results: Lean body mass increased from 42.65 +/- 2.25 (se) to 45.47 +/- 2.31 kg (P < or = 0.0001), and percent fat decreased from 42.84 +/- 1.12 to 39.95 +/- 1.34% (P = 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6-12 months of GH. Mean fasting glucose of 85.3 +/- 3.4 mg/dl, hemoglobin A1c of 5.5 +/- 0.2%, fasting insulin of 5.3 +/- 0.6 microU/ml, area under the curve for insulin of 60.4 +/- 7.5 microU/ml, and homeostasis model assessment of insulin resistance of 1.1 +/- 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T(3) increased 26.7% from 127.0 +/- 7.8 to 150.5 +/- 7.8 ng/dl (P = 0.021) with normalization in all subjects, including six (20%) with baseline T(3) values at least 2 sd below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients).
Conclusions: This multicenter study demonstrates that GH improves body composition, normalizes T(3), and is well tolerated without glucose impairment in PWS genotype adults.