Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.
BACKGROUND
Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.


OBJECTIVE
The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.


METHODS
We conducted a multicenter prospective trial.


METHODS
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.
de Lind van Wijngaarden
Roderick F A
RF
Clinical Research Fellow, Dutch Growth Research Foundation, Erasmus University Medical Center/Sophia Children's Hospital, Westzeedijk 106, 3016 AH Rotterdam, The Netherlands. r.delindvanwijngaarden@erasmusmc.nl
Siemensma
Elbrich P C
EP
Festen
Dederieke A M
DA
Otten
Barto J
BJ
van Mil
Edgar G A H
EG
Rotteveel
Joost
J
Odink
Roelof J H
RJ
Bindels-de Heus
G C B Karen
GC
van Leeuwen
Mariëtte
M
Haring
Danny A J P
DA
Bocca
Gianni
G
Houdijk
E C A Mieke
EC
Hoorweg-Nijman
J J Gera
JJ
Vreuls
René C F M
RC
Jira
Petr E
PE
van Trotsenburg
A S Paul
AS
Bakker
Boudewijn
B
Schroor
Eelco J
EJ
Pilon
Jan Willem
JW
Wit
Jan M
JM
Drop
Stenvert L S
SL
Hokken-Koelega
Anita C S
AC
D000273:Adipose Tissue / Q000033:anatomy & histology; D001724:Birth Weight; D001794:Blood Pressure; D001827:Body Height; D001835:Body Weight; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005215:Fasting; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000188:drug therapy*; D011446:Prospective Studies; D012449:Safety
D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I