medwireNews: Children born small for gestational age (SGA) have bioactive insulin-like growth-factor (IGF)1 levels within the normal reference range during the first year of growth hormone (GH) treatment, despite substantial increases in IGF-1, research shows.
Rikke Beck Jensen (Rigshospitalet, Copenhagen, Denmark) and colleagues used an IGF-1 kinase receptor activation assay, which measures the ability of IGF-1 to activate the IGF-I receptor in vitro, to determine bioactive IGF-1 concentrations in 101 children (mean age 6.2 years) from the North European Small for Gestational Age Study.
The found that, at baseline, the mean bioactive IGF-1 concentration was –1.2 standard deviation score (SDS), which was within the normal range (+/–2.0 SDS) based on measurements from 150 healthy children aged 6 to 11 years from the COPENHAGEN Puberty Study.
After 1 year of GH treatment, the bioactive IGF-1 concentration increased significantly to 1.1 SDS but remained within the normal range.
By contrast, total IGF-1 concentration was above normal, at 2.8 SDS, after 1 year of treatment, despite being within the normal range (–1.2 SDS) at baseline.
The researchers also report in The Journal of Clinical Endocrinology & Metabolism that, at 1 year, bioactive IGF-1 levels were above normal in just 15% of the children, compared with an above-normal rate of 68% for total IGF-1.
Further analysis showed that baseline bioactive IGF SDS significantly correlated with baseline height and weight SDS but not with changes in height SDS after 1 year of GH treatment.
Conversely, baseline total IGF-1 SDS was not associated with baseline height or weight SDS but inversely correlated with changes in height SDS at 1 year.
The stronger correlation between bioactive IGF and height and weight before GH treatment suggests “that bioactive IGF reflects the biological [activity of] IGF-1 and the endogenous secretion of GH”, Jensen et al remark.
They add: “On the other hand, the IGF-1 concentration was associated with change in height during the first year of treatment with supra-physiological GH doses which may mirror the relation between IGF-1 and insulin sensitivity.”
Indeed, the team found that insulin sensitivity was inversely associated with both bioactive IGF SDS and total IGF-1 SDS, and was positively associated change in height during the first year of treatment.
Jensen and co-authors note that guidelines recommend keeping IGF-1 within the normal physiological range during GH treatment, because of safety concerns raised by epidemiological studies.
“To our knowledge this is the first study to explore bioactive IGF in a cohort of short GH treated SGA children, and we find it of interest that bioactive IGF stays within the normal range during the first year of treatment with GH”, Jensen and co-authors conclude.
They add: “Further studies are needed to investigate the potential clinical role of bioactive IGF-1 in the monitoring of GH treated children.”
By Laura Cowen
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J Clin Endocrinol Metab 2019; doi:10.1210/clinem/dgz118