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

• Published in: The journal of clinical endocrinology and metabolism Vol. 93; no. 4; pp. 1238 - 1245
• Main Authors: Mogul, Harriette R, Lee, Phillip D. K, Whitman, Barbara Y, Zipf, William B, Frey, Michael, Myers, Susan, Cahan, Mindy, Pinyerd, Belinda, Southren, A. Louis
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.04.2008; Copyright by The Endocrine Society
• Subjects: Adipose Tissue - metabolism; Adolescent; Adult; Biological and medical sciences; Body Composition - drug effects; Bone Density; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Human Growth Hormone - adverse effects; Human Growth Hormone - deficiency; Human Growth Hormone - therapeutic use; Humans; Insulin Resistance; Male; Medical sciences; Middle Aged; Prader-Willi Syndrome - drug therapy; Prader-Willi Syndrome - metabolism; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Triiodothyronine - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; United States; North America; America; Endocrinopathy; Adipose tissue; Multicenter study; Diseases of the osteoarticular system; Glucose; Fat mass; Result; Improvement; Lean body mass; Adult; Clinical trial; Serum; Triiodothyronine; Complex syndrome; Prader Labhart Willi syndrome; Nutritional status; Human; Deficiency; Nutrition disorder; Metabolic diseases; Genetic disease; Somatotropin; Treatment; Adenohypophyseal hormone; Thyroid hormone; Endocrinology
• DOI: 10.1210/jc.2007-2212
• ISSN: 0021-972X

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.