Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators.
OBJECTIVE
In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV).


METHODS
Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard].


RESULTS
During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant.


CONCLUSIONS
During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.
Rekers-Mombarg
L T
LT
Department of Pediatrics of the University Hospital of Leiden, The Netherlands.
Massa
G G
GG
Wit
J M
JM
Matranga
A M
AM
Buckler
J M
JM
Butenandt
O
O
Chaussain
J L
JL
Frisch
H
H
Leiberman
E
E
Yturriaga
R
R
Aarskog
D
D
Chatelain
P G
PG
Colle
M
M
Dacou-Voutetakis
C
C
Delemarre-van de Waal
H A
HA
Girard
F
F
Gosen
J J
JJ
Irle
U
U
Jansen
M
M
Jean
R
R
Job
J C
JC
Kaar
M L
ML
Kollemann
F
F
Lenko
H L
HL
Waelkens
J J
JJ
D001827:Body Height / Q000187:drug effects; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation; D006128:Growth / Q000187:drug effects*; D006130:Growth Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013006:Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D012044:Regression Analysis
D013006:Growth Hormone