Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA
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Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA. / Wegmann, Mathilde Gersel; Jensen, Rikke Beck; Thankamony, Ajay; Frystyk, Jan; Roche, Edna; Hoey, Hilary; Kirk, Jeremy; Shaikh, Guftar; Ivarsson, Sten-A; Söder, Olle; Dunger, David B; Juul, Anders.
I: Journal of Clinical Endocrinology and Metabolism, Bind 105, Nr. 4, 2020, s. e1291–e1298.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA
AU - Wegmann, Mathilde Gersel
AU - Jensen, Rikke Beck
AU - Thankamony, Ajay
AU - Frystyk, Jan
AU - Roche, Edna
AU - Hoey, Hilary
AU - Kirk, Jeremy
AU - Shaikh, Guftar
AU - Ivarsson, Sten-A
AU - Söder, Olle
AU - Dunger, David B
AU - Juul, Anders
N1 - © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Biomarkers/blood
KW - Body Height/drug effects
KW - Case-Control Studies
KW - Child
KW - Female
KW - Follow-Up Studies
KW - Growth Disorders/blood
KW - Human Growth Hormone/administration & dosage
KW - Humans
KW - Infant, Small for Gestational Age/blood
KW - Insulin-Like Growth Factor Binding Protein 3/blood
KW - Insulin-Like Growth Factor I/analysis
KW - Male
KW - Prognosis
U2 - 10.1210/clinem/dgz118
DO - 10.1210/clinem/dgz118
M3 - Journal article
C2 - 31665326
VL - 105
SP - e1291–e1298
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -
ID: 259057706