Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency.
BACKGROUND
The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).


OBJECTIVE
The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.


METHODS
A randomized, controlled, long-term multicenter trial was conducted in Sweden.


METHODS
Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.


METHODS
A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.


METHODS
We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.


RESULTS
After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.


CONCLUSIONS
GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
Albertsson-Wikland
Kerstin
K
Göteborg Pediatric Growth Research Center/Växthuset, Department of Pediatrics, The Sahlgrenska Academy at University of Gothenburg, and The Queen Silvia Children's Hospital, Göteborg, Sweden. kerstin.albertsson-wikland@pediat.gu.se
Aronson
A Stefan
AS
Gustafsson
Jan
J
Hagenäs
Lars
L
Ivarsson
Sten A
SA
Jonsson
Björn
B
Kriström
Berit
B
Marcus
Claude
C
Nilsson
Karl Olof
KO
Ritzén
E Martin
EM
Tuvemo
Torsten
T
Westphal
Otto
O
Aman
Jan
J
D000328:Adult; D001827:Body Height / Q000187:drug effects*; D015992:Body Mass Index; D002648:Child; D004392:Dwarfism / Q000188:drug therapy*; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010290:Parents; D018579:Patient Selection; D011627:Puberty; D013548:Sweden; D016896:Treatment Outcome
D019382:Human Growth Hormone