title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults.
  
  
  METHODS
  We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods.
  
  
  METHODS
  The study was conducted at outpatient treatment facilities at four U.S. academic medical centers.
  
  
  METHODS
  Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, Division of Endocrinology, New York Medical College, 490 Munger Pavilion, Valhalla, New York 10595, USA. hrmogul@nymc.edu
authors.forename: Harriette R
authors.initials: HR
authors.lastname: Mogul
authors.forename: Phillip D K
authors.initials: PD
authors.lastname: Lee
authors.forename: Barbara Y
authors.initials: BY
authors.lastname: Whitman
authors.forename: William B
authors.initials: WB
authors.lastname: Zipf
authors.forename: Michael
authors.initials: M
authors.lastname: Frey
authors.forename: Susan
authors.initials: S
authors.lastname: Myers
authors.forename: Mindy
authors.initials: M
authors.lastname: Cahan
authors.forename: Belinda
authors.initials: B
authors.lastname: Pinyerd
authors.forename: A Louis
authors.initials: AL
authors.lastname: Southren
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D015519:Bone Density; D005260:Female; D005947:Glucose / Q000378:metabolism*; D019382:Human Growth Hormone / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011218:Prader-Willi Syndrome / Q000188:drug therapy* / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D011994:Recombinant Proteins; D014284:Triiodothyronine; D019382:Human Growth Hormone; D005947:Glucose