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.
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.
Mogul
Harriette R
HR
Department of Medicine, Division of Endocrinology, New York Medical College, 490 Munger Pavilion, Valhalla, New York 10595, USA. hrmogul@nymc.edu
Lee
Phillip D K
PD
Whitman
Barbara Y
BY
Zipf
William B
WB
Frey
Michael
M
Myers
Susan
S
Cahan
Mindy
M
Pinyerd
Belinda
B
Southren
A Louis
AL
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*
D011994:Recombinant Proteins; D014284:Triiodothyronine; D019382:Human Growth Hormone; D005947:Glucose