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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

Departments of Medicine (H.R.M., A.L.S.) and Pediatrics (M.F.), New York Medical College, Valhalla, New York 10595; Department of Pediatrics (P.D.K.L., M.C.), David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095; Department of Pediatrics (B.Y.W., S.M.), St. Louis University, St. Louis, Missouri 63104; and Department of Pediatrics (W.B.Z., B.P.), Ohio State University, Columbus, Ohio 43210

Address all correspondence and requests for reprints to: Harriette R. Mogul, M.D., M.P.H., Division of Endocrinology, New York Medical College, 490 Munger Pavilion, Valhalla, New York 10595. E-mail: hrmogul{at}nymc.edu.

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 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 µU/ml, area under the curve for insulin of 60.4 ± 7.5 µU/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.