Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity.
BACKGROUND
Children with severe IGF-I deficiency due to congenital or acquired defects in GH action have short stature that cannot be remedied by GH treatment.


OBJECTIVE
The objective of the study was to examine the long-term efficacy and safety of recombinant human IGF-I (rhIGF-I) therapy for short children with severe IGF-I deficiency.


METHODS
Seventy-six children with IGF-I deficiency due to GH insensitivity were treated with rhIGF-I for up to 12 yr under a predominantly open-label design.


METHODS
The study was conducted at general clinical research centers and with collaborating endocrinologists.


METHODS
Entry criteria included: age older than 2 yr, sd scores for height and circulating IGF-I concentration less than -2 for age and sex, and evidence of resistance to GH.


METHODS
rhIGF-I was administered sc in doses between 60 and 120 microg/kg twice daily.


METHODS
Height velocity, skeletal maturation, and adverse events were measured.


RESULTS
Height velocity increased from 2.8 cm/yr on average at baseline to 8.0 cm/yr during the first year of treatment (P < 0.0001) and was dependent on the dose administered. Height velocities were lower during subsequent years but remained above baseline for up to 8 yr. The most common adverse event was hypoglycemia, which was observed both before and during therapy. It was reported by 49% of treated subjects. The next most common adverse events were injection site lipohypertrophy (32%) and tonsillar/adenoidal hypertrophy (22%).


CONCLUSIONS
Treatment with rhIGF-I stimulates linear growth in children with severe IGF-I deficiency due to GH insensitivity. Adverse events are common but are rarely of sufficient severity to interrupt or modify treatment.
Chernausek
Steven D
SD
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. steven.chernausek@cchmc.org
Backeljauw
Philippe F
PF
Frane
James
J
Kuntze
Joyce
J
Underwood
Louis E
LE
D000293:Adolescent; D000328:Adult; D001846:Bone Development / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000254:growth & development; D046150:Laron Syndrome / Q000188:drug therapy*; D008134:Long-Term Care; D008297:Male; D010919:Placebos; D011994:Recombinant Proteins / Q000627:therapeutic use
D010919:Placebos; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I