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Increases in bioactive IGF do not parallel increases in total IGF-I during growth hormone treatment of children born SGA

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  • Mathilde Gersel Wegmann
  • Rikke Beck Jensen
  • Ajay Thankamony
  • Jan Frystyk
  • Edna Roche
  • Hilary Hoey
  • Jeremy Kirk
  • Guftar Shaikh
  • Sten-A Ivarsson
  • Olle Söder
  • David B Dunger
  • Anders Juul
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BACKGROUND: Some children born small for gestational age (SGA) experience supra-physiological insulin-like growth factor-I (IGF-I) concentrations during GH treatment. However, measurements of total IGF-I concentrations may not reflect the bioactive fraction of IGF-I which reaches the IGF-I receptor at target organs. We examined endogenous IGF-bioactivity using an IGF-I kinase receptor activation (KIRA) assay that measures the ability of IGF-I to activate the IGF-IR in vitro.

AIM: To compare responses of bioactive IGF and total IGF-I concentrations in short GH treated SGA children in the North European Small for Gestational Age Study (NESGAS).

MATERIAL AND METHOD: In NESGAS, short SGA children (n = 101, 61 males) received GH at 67 µg/kg/day for 1 year. IGF-I concentrations were measured by Immulite immunoassay and bioactive IGF by in-house KIRA assay.

RESULTS: Bioactive IGF increased with age in healthy pre-pubertal children (n = 94). SGA children had low-normal bioactive IGF levels at baseline (-0.12 (1.8 SD), increasing significantly after one year of high-dose GH treatment to 1.1 (1.4) SD, P < 0.01. Following high-dose GH, 68% (n = 65) of SGA children had a total IGF-I concentration >2SD (mean IGF-I 2.8 SDS), whereas only 15% (n = 15) had levels of bioactive IGF slightly above normal reference values. At baseline, bioactive IGF (SDS) was significantly correlated to height (SDS) (r = 0.29, P = 0.005), in contrast to IGF-I (SDS) (r = 0.17, P = 0.10). IGF-I (SDS) was inversely correlated to delta height (SDS) after one year of high-dose GH treatment (r = -0.22, P = 0.02).

CONCLUSION: In contrast to total IGF-I concentrations, bioactive IGF stayed within the normal reference ranges for most SGA children during the first year of GH treatment.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue number4
Pages (from-to)1-8
ISSN0021-972X
DOIs
Publication statusPublished - 1 Apr 2020

ID: 58487940