TY - JOUR
T1 - Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome
AU - de Lind van Wijngaarden, Roderick F A
AU - Siemensma, Elbrich P C
AU - Festen, Dederieke A M
AU - Otten, Barto J
AU - van Mil, Edgar G A H
AU - Rotteveel, Joost
AU - Odink, Roelof J H
AU - Bindels-de Heus, G C B Karen
AU - van Leeuwen, Mariëtte
AU - Haring, Danny A J P
AU - Bocca, Gianni
AU - Houdijk, E C A Mieke
AU - Hoorweg-Nijman, J J Gera
AU - Vreuls, René C F M
AU - Jira, Petr E
AU - van Trotsenburg, A S Paul
AU - Bakker, Boudewijn
AU - Schroor, Eelco J
AU - Pilon, Jan Willem
AU - Wit, Jan M
AU - Drop, Stenvert L S
AU - Hokken-Koelega, Anita C S
PY - 2009/11
Y1 - 2009/11
N2 - BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.SETTING: We conducted a multicenter prospective trial.DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.
AB - BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.SETTING: We conducted a multicenter prospective trial.DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.
KW - Adipose Tissue/anatomy & histology
KW - Birth Weight
KW - Blood Pressure
KW - Body Height
KW - Body Weight
KW - Bone Density
KW - Child
KW - Child, Preschool
KW - Drug Administration Schedule
KW - Fasting
KW - Human Growth Hormone/administration & dosage
KW - Humans
KW - Insulin-Like Growth Factor Binding Protein 3/blood
KW - Insulin-Like Growth Factor I/metabolism
KW - Prader-Willi Syndrome/drug therapy
KW - Prospective Studies
KW - Safety
U2 - 10.1210/jc.2009-0454
DO - 10.1210/jc.2009-0454
M3 - Article
C2 - 19837938
SN - 0021-972X
VL - 94
SP - 4205
EP - 4215
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 11
ER -