ESPE Abstracts (2019) 92 RFC14.5

Bioactive IGF-I Concentration Compared to Total IGF-I Concentration Before and After 1 Year of High-Dose Growth Hormone in Short Children Born Small for Gestational Age - North European SGA Study (NESGAS)

Rikke Beck Jensen1, Mathilde Gersel Wegmann1, Ajay Thankamony2, Edna Roche3, Hilary Hoey 3, Jeremy Kirk4, Sten-A. Ivarsson5, Olle Söder6, Jan Frystyk7, David B. Dunger2, Anders Juul1


1Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2Department of Pediatrics, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. 3Department of Pediatrics, The National Children's Hospital, University of Dublin, Trinity College, Dublin, Ireland. 4Department of Endocrinology, Birmingham Children's Hospital, Birmingham, United Kingdom. 5Department of Clinical Sciences, Endocrine and Diabetes Unit, University of Lund, Malmoe, Sweden. 6Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet & University Hospital, Stockholm, Sweden. 7Department of Endocrinology, Odense University Hospital & Department of Clinical Research, University of Southern Denmark, Odense, Denmark


Background: Children born small for gestational age (SGA) exhibit wide variations in the activity of growth hormone (GH)/insulin–like growth factor–I (IGF-I) axis and this heterogeneity may result in supra physiological concentrations of IGF-I during GH treatment. The long-term effects of elevated IGF-I levels has been a matter of concern. We explored the variations in total IGF-I and bioactive IGF-I and the associations with growth and glucose metabolism in response to a fixed GH dose over 1 year in SGA children.

Methods: The North European Small for Gestational Age Study (NESGAS) is a multicenter study (n=101, 61 males) of GH therapy in prepubertal short SGA children. They received GH therapy at 67µg/kg/day for 1 year. IGF-I was measured by a commercial immunoassay and bioactive IGF-I was measured using the IGF-I kinase receptor activation assay (KIRA).

Results: Bioactive IGF-I at baseline was significantly lower among boys compared to girls (median (25-75 percentile) (-1.4SDS (-2.7 to -0.2)) and -0.2SDS (-1.4–0.4), respectively) (P=0.002). In contrast, no difference in bioactive IGF-I SDS according to gender was present after one year of GH treatment. No significant differences in total IGF-I were found between the genders before and after one year of high-dose GH treatment.

Bioactive IGF-I (SDS) was significantly correlated to height (SDS) at baseline and the association was stronger than the correlation between total IGF-I (SDS) and height (r:0.29, P=0.005 and r:0.17, P=0.10, respectively). After one year of high-dose GH treatment 68% (N=65) of the children in the entire cohort had increased levels of total IGF-I above + 2SD, whereas only 15% (N=15) had levels of bioactive IGF-I above the normal reference. Change in height (SDS) correlated significantly with baseline total IGF-I (SDS) (r:-0.25, P=0.02) but not with bioactive IGF-I (SDS) (r:-0.11, P=0.30). Bioactive IGF-I (SDS) correlated positively with total IGF-I (SDS) (r:0.35, P=0.001) and IGFBP-3 (SDS) (r:0.26, P=0.01) and correlated negatively with insulin sensitivity (HOMA-S) (r:-0.29, P=0.007) and IGFBP-1 (r:-0.18, P=0.08).

Conclusion: Bioactive IGF-I showed a stronger association with height compared to total IGF-I at start, but was not a good predictor of the one year response to high-dose GH treatment. Reassuringly, we found that only 15 % of the GH treated SGA children had supra-physiological levels of bioactive IGF-I after one year of high-dose treatment in contrast to elevated total IGF-I levels in 68% of the patients.