{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:31:19Z","timestamp":1790195479785,"version":"4.1.0"},"reference-count":31,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","award":["F-22717-20"],"award-info":[{"award-number":["F-22717-20"]}],"id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Material and method<\/jats:title>\n                  <jats:p>In NESGAS, short SGA children (n = 101, 61 males) received GH at 67 \u00b5g\/kg\/day for 1 year. IGF-I concentrations were measured by Immulite immunoassay and bioactive IGF by in-house KIRA assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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 &amp;lt; 0.01. Following high-dose GH, 68% (n = 65) of SGA children had a total IGF-I concentration &amp;gt;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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz118","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T19:10:05Z","timestamp":1572462605000},"page":"e1291-e1298","source":"Crossref","is-referenced-by-count":18,"title":["Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA"],"prefix":"10.1210","volume":"105","author":[{"given":"Mathilde Gersel","family":"Wegmann","sequence":"first","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-672X","authenticated-orcid":false,"given":"Rikke Beck","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Thankamony","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1481-3278","authenticated-orcid":false,"given":"Jan","family":"Frystyk","sequence":"additional","affiliation":[{"name":"Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark"},{"name":"Endocrine Research Unit, Department of Endocrinology, Odense University Hospital & Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7266-8649","authenticated-orcid":false,"given":"Edna","family":"Roche","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The National Children\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-1659","authenticated-orcid":false,"given":"Hilary","family":"Hoey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The National Children\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7183-7727","authenticated-orcid":false,"given":"Jeremy","family":"Kirk","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Birmingham Children\u2019s Hospital, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-3334","authenticated-orcid":false,"given":"Guftar","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Royal Hospital for Children, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten-A","family":"Ivarsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Endocrine and Diabetes Unit, University of Lund, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"S\u00f6der","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-3495","authenticated-orcid":false,"given":"David B","family":"Dunger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom"},{"name":"Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0534-4350","authenticated-orcid":false,"given":"Anders","family":"Juul","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"issue":"6 Pt 1","key":"2021122209575167500_CIT0001","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1542\/peds.111.6.1253","article-title":"International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001","volume":"111","author":"Lee","year":"2003","journal-title":"Pediatrics."},{"issue":"3","key":"2021122209575167500_CIT0002","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1210\/jc.2006-2017","article-title":"Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society","volume":"92","author":"Clayton","year":"2007","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122209575167500_CIT0003","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1159\/000322878","article-title":"A comparison of different definitions of growth response in short prepubertal children treated with growth hormone","volume":"75","author":"Bang","year":"2011","journal-title":"Horm Res Paediatr."},{"issue":"1","key":"2021122209575167500_CIT0004","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1159\/000353438","article-title":"Baseline IGF-I levels determine insulin secretion and insulin sensitivity during the first year on growth hormone therapy in children born small for gestational age. Results from a North European Multicentre Study (NESGAS)","volume":"80","author":"Jensen","year":"2013","journal-title":"Horm Res Paediatr."},{"issue":"3","key":"2021122209575167500_CIT0005","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1210\/jc.2009-1378","article-title":"Insulin-like growth factor-I and cancer mortality in older men","volume":"95","author":"Major","year":"2010","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122209575167500_CIT0006","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/cen.12962","article-title":"Insulin-like growth factor I and risk of incident cancer in elderly men - results from MrOS (Osteoporotic Fractures in Men) in Sweden","volume":"84","author":"Carlzon","year":"2016","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"9","key":"2021122209575167500_CIT0007","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1210\/jc.2011-1377","article-title":"Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality","volume":"96","author":"Burgers","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122209575167500_CIT0008","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-17-0430","article-title":"Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting","volume":"177","author":"Gravholt","year":"2017","journal-title":"Eur J Endocrinol."},{"issue":"6","key":"2021122209575167500_CIT0009","doi-asserted-by":"crossref","first-page":"E1072","DOI":"10.1210\/jc.2012-3888","article-title":"GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome","volume":"98","author":"Deal","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122209575167500_CIT0010","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ghir.2004.06.001","article-title":"Free insulin-like growth factors \u2013 measurements and relationships to growth hormone secretion and glucose homeostasis","volume":"14","author":"Frystyk","year":"2004","journal-title":"Growth Horm IGF Res."},{"issue":"1","key":"2021122209575167500_CIT0011","first-page":"3","article-title":"Insulin-like growth factors and their binding proteins: biological actions","volume":"16","author":"Jones","year":"1995","journal-title":"Endocr Rev."},{"issue":"6","key":"2021122209575167500_CIT0012","doi-asserted-by":"crossref","first-page":"E1149","DOI":"10.1152\/ajpendo.00410.2002","article-title":"A highly sensitive and specific assay for determination of IGF-I bioactivity in human serum","volume":"284","author":"Chen","year":"2003","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"3-4","key":"2021122209575167500_CIT0013","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3109\/08977194.2014.939806","article-title":"Cell-based assays for IGF-I bioactivity measurement: overview, limitations and current trends","volume":"32","author":"Ramadhin","year":"2014","journal-title":"Growth Factors."},{"issue":"2","key":"2021122209575167500_CIT0014","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1530\/EJE-15-0048","article-title":"Changes in circulating IGF1 receptor stimulating activity do not parallel changes in total IGF1 during GH treatment of GH-deficient adults","volume":"173","author":"Varewijck","year":"2015","journal-title":"Eur J Endocrinol."},{"issue":"8","key":"2021122209575167500_CIT0015","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1210\/jc.2015-1410","article-title":"IGF-1 levels, complex formation, and IGF bioactivity in growth hormone-treated children with Prader-Willi syndrome","volume":"100","author":"Bakker","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"7","key":"2021122209575167500_CIT0016","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1210\/jc.2011-0051","article-title":"IGF-I bioactivity better reflects growth hormone deficiency than total IGF-I","volume":"96","author":"Varewijck","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122209575167500_CIT0017","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1210\/jc.2011-1995","article-title":"Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study","volume":"97","author":"Carel","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122209575167500_CIT0018","doi-asserted-by":"crossref","first-page":"E213","DOI":"10.1210\/jc.2011-2882","article-title":"Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study","volume":"97","author":"S\u00e4vendahl","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122209575167500_CIT0019","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1210\/jc.2016-2046","article-title":"Cancer risks in patients treated with growth hormone in childhood: the SAGhE European Cohort Study","volume":"102","author":"Swerdlow","year":"2017","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122209575167500_CIT0020","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s11102-013-0529-6","article-title":"Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS)","volume":"17","author":"Mo","year":"2014","journal-title":"Pituitary."},{"issue":"5","key":"2021122209575167500_CIT0021","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1530\/EJE-12-0106","article-title":"Serum IGF1 and insulin levels in girls with normal and precocious puberty","volume":"166","author":"S\u00f8rensen","year":"2012","journal-title":"Eur J Endocrinol."},{"issue":"8","key":"2021122209575167500_CIT0022","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1210\/jc.2009-0313","article-title":"Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty","volume":"94","author":"S\u00f8rensen","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122209575167500_CIT0023","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1471-2369-14-80","article-title":"Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study","volume":"14","author":"Reinhard","year":"2013","journal-title":"BMC Nephrol."},{"issue":"1","key":"2021122209575167500_CIT0024","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1210\/jc.2014-2558","article-title":"The introduction of the IDS-iSYS total IGF-1 assay may have far-reaching consequences for diagnosis and treatment of GH deficiency","volume":"100","author":"Varewijck","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122209575167500_CIT0025","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jpeds.2010.02.028","article-title":"Growth hormone treatment in children is not associated with an increase in the incidence of cancer: experience from KIGS (Pfizer International Growth Database)","volume":"157","author":"Wilton","year":"2010","journal-title":"J Pediatr."},{"issue":"4","key":"2021122209575167500_CIT0026","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ghir.2014.02.001","article-title":"Association between growth hormone therapy and mortality, cancer and cardiovascular risk: systematic review and meta-analysis","volume":"24","author":"Deodati","year":"2014","journal-title":"Growth Horm IGF Res."},{"issue":"6","key":"2021122209575167500_CIT0027","doi-asserted-by":"crossref","first-page":"E967","DOI":"10.1152\/ajpendo.2000.278.6.E967","article-title":"Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities","volume":"278","author":"Baxter","year":"2000","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"8","key":"2021122209575167500_CIT0028","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1210\/jc.2015-1410","article-title":"IGF-1 levels, complex formation, and IGF bioactivity in growth hormone-treated children with Prader-Willi syndrome","volume":"100","author":"Bakker","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2021122209575167500_CIT0029","doi-asserted-by":"crossref","first-page":"E1149","DOI":"10.1152\/ajpendo.00410.2002","article-title":"A highly sensitive and specific assay for determination of IGF-I bioactivity in human serum","volume":"284","author":"Chen","year":"2003","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"7","key":"2021122209575167500_CIT0030","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1210\/jc.2007-2454","article-title":"Normal values of circulating insulin-like growth factor-I bioactivity in the healthy population: comparison with five widely used IGF-I immunoassays","volume":"93","author":"Brugts","year":"2008","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021122209575167500_CIT0031","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrendo.2010.171","article-title":"Growth hormone, the insulin-like growth factor axis, insulin and cancer risk","volume":"7","author":"Clayton","year":"2011","journal-title":"Nat Rev Endocrinol."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgz118\/30321793\/dgz118.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1291\/41860041\/jcem_105_4_e1291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1291\/41860041\/jcem_105_4_e1291.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T18:03:18Z","timestamp":1640196198000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/4\/e1291\/5608612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,29]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,10,29]]},"published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgz118","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2019,10,29]]}}}