Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: Results from the United States multicenter trial

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 recombinantGH(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: Leanbodymass increased from 42.65 +/-2.25 (SE) to 45.47 +/-2.31kg(P <= 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 mu U/ml, area under the curve for insulin of 60.4 +/-7.5 mu U/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 T3 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 T3 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 T3, and is well tolerated without glucose impairment in PWS genotype adults.