{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:21:27Z","timestamp":1783488087603,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values &gt; 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p &lt; 0.001. After 24 months of treatment, the values were: 47 (33%) &gt; 97th percentile by local vs. 6 (4.2%) by population standards; p &lt; 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 &gt; 97th percentile according to the local reference ranges and five (13%) &gt; 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.<\/jats:p>","DOI":"10.3390\/jcm12134392","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T01:02:41Z","timestamp":1688086961000},"page":"4392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland"],"prefix":"10.3390","volume":"12","author":[{"given":"Marta","family":"Gli\u0144ska","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Endocrinology, Diabetology, Metabolic Disorders and Cardiology of the Developmental Age, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczys\u0142aw","family":"Walczak","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Endocrinology, Diabetology, Metabolic Disorders and Cardiology of the Developmental Age, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Wikiera","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetology of Children and Adolescents, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Pyr\u017cak","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Endocrinology, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Majcher","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Endocrinology, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Paluchowska","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Endocrinology, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Gawlik","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Paediatric Endocrinology with Division of Sex Development Disorders, Upper Silesia Children\u2019s Health Centre, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Antosz","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Paediatric Endocrinology with Division of Sex Development Disorders, Upper Silesia Children\u2019s Health Centre, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Kusz","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Paediatric Endocrinology with Division of Sex Development Disorders, Upper Silesia Children\u2019s Health Centre, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6316-5342","authenticated-orcid":false,"given":"Artur","family":"Bossowski","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Sto\u017cek","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"W\u0119drychowicz","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Children and Young Adults, Collegium Medicum, Jagiellonian University, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Starzyk","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Children and Young Adults, Collegium Medicum, Jagiellonian University, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-6798","authenticated-orcid":false,"given":"El\u017cbieta","family":"Petriczko","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Endocrinology, Diabetology, Metabolic Disorders and Cardiology of the Developmental Age, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s13669-013-0041-z","article-title":"Intrauterine Growth Restriction (IUGR): Etiology and Diagnosis","volume":"2","author":"Suhag","year":"2013","journal-title":"Curr. Obstet. Gynecol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/er.2006-0039","article-title":"Small for Gestational Age: Short Stature and Beyond","volume":"28","author":"Saenger","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1210\/jc.2006-1073","article-title":"Risk Factors for Diabetes Mellitus Type 2 and Metabolic Syndrome Are Comparable for Previously Growth Hormone-Treated Young Adults Born Small for Gestational Age (SGA) and Untreated Short SGA Controls","volume":"92","author":"Bannink","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","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, 24 April\u20131 October 2001","volume":"111","author":"Lee","year":"2003","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1515\/jpem-2021-0389","article-title":"Growth response to growth hormone (GH) treatment in children with GH deficiency (GHD) and those with idiopathic short stature (ISS) based on their pretreatment insulin-like growth factor 1 (IGFI) levels and at diagnosis and IGFI increment on treatment","volume":"34","author":"Soliman","year":"2021","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1210\/jcem.87.1.8150","article-title":"Effects of Dose and Gender on the Growth and Growth Factor Response to GH in GH-Deficient Children: Implications for Efficacy and Safety","volume":"87","author":"Cohen","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/1534735403259152","article-title":"Insulin and Cancer","volume":"2","author":"Boyd","year":"2003","journal-title":"Integr. Cancer Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1210\/jc.2009-2139","article-title":"Variable Degree of Growth Hormone (GH) and Insulin-Like Growth Factor (IGF) Sensitivity in Children with Idiopathic Short Stature Compared with GH-Deficient Patients: Evidence from an IGF-Based Dosing Study of Short Children","volume":"95","author":"Cohen","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1210\/jc.2007-0204","article-title":"Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study","volume":"92","author":"Cohen","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s11102-011-0343-y","article-title":"How useful are serum IGF-I measurements for managing GH replacement therapy in adults and children?","volume":"15","author":"Cohen","year":"2012","journal-title":"Pituitary"},{"key":"ref_11","unstructured":"(2023, May 12). Leczenie Hormonem Wzrostu Niskoros\u0142ych Dzieci Urodzonych Jako Zbyt Ma\u0142e w Por\u00f3wnaniu Do Czasu Trwania Ci\u0105\u017cy (SGA Lub IUGR) (ICD-10 R 62.9). Obwieszczenie Ministra Zdrowia z Dnia 19 Grudnia 2014 r. w Sprawie Wykazu Refundowanych Lek\u00f3w, \u015arodk\u00f3w Spo\u017cywczych, Available online: https:\/\/www.gov.pl\/attachment\/e48d74fb-7298-472d-adc9-ffc096d91b6d."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gli\u0144ska, M., Walczak, M., Wikiera, B., Pyr\u017cak, B., Majcher, A., Paluchowska, M., Gawlik, A., Antosz, A., Kusz, M., and Bossowski, A. (2022). Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland. J. Clin. Med., 11.","DOI":"10.3390\/jcm11113096"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ghir.2012.04.005","article-title":"Serum insulin-like growth factor-I (IGF-I) reference ranges for chemiluminescence assay in childhood and adolescence. Data from a population of in- and out-patients","volume":"22","author":"Bedogni","year":"2012","journal-title":"Growth Horm. IGF Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0021-9258(17)40889-1","article-title":"The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin","volume":"253","author":"Rinderknecht","year":"1978","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4248\/BR201303003","article-title":"Autocrine and Paracrine Actions of IGF-I Signaling in Skeletal Development","volume":"1","author":"Wang","year":"2013","journal-title":"Bone Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1053\/beem.2002.0212","article-title":"IGFs and IGFBPs: Role in health and disease","volume":"16","author":"Monzavi","year":"2002","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1373\/clinchem.2010.150631","article-title":"Consensus Statement on the Standardization and Evaluation of Growth Hormone and Insulin-like Growth Factor Assays","volume":"57","author":"Clemmons","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1159\/000071871","article-title":"Serum Insulin-Like Growth Factor I Reference Values for an Automated Chemiluminescence Immunoassay System: Results from a Multicenter Study","volume":"60","author":"Brabant","year":"2003","journal-title":"Horm. Res. Paediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1136\/mp.54.5.311","article-title":"Insulin-like growth factor 1 (IGF-1): A growth hormone","volume":"54","author":"Laron","year":"2001","journal-title":"Mol. Pathol."},{"key":"ref_20","first-page":"47","article-title":"Endokrynologia Pediatryczna Pediatric Endocrinology Budowa i funkcja insulinopodobnych czynnik\u00f3w wzrostowych oraz objawy kliniczne","volume":"9","author":"Ziora","year":"2010","journal-title":"Endokrynol. Pediatryczna"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1210\/jc.2007-1534","article-title":"The Role of Recombinant Human Insulin-Like Growth Factor-I in Treating Children with Short Stature","volume":"93","author":"Misra","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000502739","article-title":"Current Insights into the Role of the Growth Hormone-Insulin-Like Growth Factor System in Short Children Born Small for Gestational Age","volume":"92","author":"Renes","year":"2019","journal-title":"Horm. Res. Paediatr."},{"key":"ref_23","first-page":"3990","article-title":"Consensus Guidelines for the Diagnosis and Treatment of Growth Hormone (GH) Deficiency in Childhood and Adolescence: Summary Statement of the GH Research Society","volume":"85","author":"Israel","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","first-page":"18","article-title":"Wska\u017aniki rozwoju somatycznego dzieci i m\u0142odzie\u017cy Warszawskiej","volume":"5","author":"Palczewska","year":"2001","journal-title":"Med. Wieku Rozwoj."},{"key":"ref_25","unstructured":"Siemens Healthineers (2023, May 12). IMMULITE 2000 XPi Immunoassay System. Available online: https:\/\/www.siemens-healthineers.com\/immunoassay\/systems\/immulite-2000-xpi-immunoassay-system."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kim, S.K., and Jeong, T.D. (2020). Performance Evaluation of the Elecsys Growth Hormone and Insulin-like Growth Factor 1 Assay. Clin. Lab., 66.","DOI":"10.7754\/Clin.Lab.2019.191149"},{"key":"ref_27","unstructured":"(2023, May 12). Elecsys IGF-1. Elecsys IGF-1.: 1-6. Available online: https:\/\/labogids.sintmaria.be\/sites\/default\/files\/files\/igf-1_2019-01_v1.pdf."},{"key":"ref_28","unstructured":"(2023, May 12). Immunoassays Diasource. IGF-1-RIA-CT. Available online: https:\/\/diasource-diagnostics.com\/products\/918-igf-1-ria-ct-96-tests?I."},{"key":"ref_29","first-page":"235","article-title":"A Model for Interaction Design of Personalised Knowledge Systems in the Health Domain. Electronic Healthcare","volume":"Volume 69","author":"Lindgren","year":"2011","journal-title":"Electronic Healthcare, Proceedings of the Third International Conference, eHealth 2010, Casablanca, Morocco, 13\u201315 December 2010"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2018-00083","article-title":"Children Born Small for Gestational Age: Differential Diagnosis, Molecular Genetic Evaluation, and Implications","volume":"39","author":"Finken","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1159\/000334651","article-title":"Evolution of IGF-1 in Children Born Small for Gestational Age and with Growth Retardation, Treated by Growth Hormone Adapted to IGF-1 Levels after 1 Year","volume":"76","author":"Cabrol","year":"2011","journal-title":"Horm. Res. Paediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1210\/jc.2013-3059","article-title":"Reference Intervals for Insulin-like Growth Factor-1 (IGF-I) From Birth to Senescence: Results From a Multicenter Study Using a New Automated Chemiluminescence IGF-I Immunoassay Conforming to Recent International Recommendations","volume":"99","author":"Bidlingmaier","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000080760","article-title":"The Role of Insulin-Like Growth Factor I Monitoring in Growth Hormone-Treated Children","volume":"62","author":"Park","year":"2004","journal-title":"Horm. Res. Paediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13633-018-0064-3","article-title":"Poor growth response during the first year of growth hormone treatment in short prepubertal children with growth hormone deficiency and born small for gestational age: A comparison of different criteria","volume":"2018","author":"Straetemans","year":"2018","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1007\/s11102-021-01173-0","article-title":"Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors\u2014A review of research and clinical practice","volume":"24","author":"Boguszewski","year":"2021","journal-title":"Pituitary"},{"key":"ref_36","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."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jacl.2017.05.010","article-title":"Growth hormone activates hepatic and cerebral cholesterol metabolism in small-for-gestational age children without catch-up growth","volume":"11","author":"Hirayama","year":"2017","journal-title":"J. Clin. Lipidol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.pcd.2019.03.012","article-title":"Decreased insulin sensitivity and abnormal glucose metabolism start in preadolescence in low-birth-weight children\u2014Meta-analysis and systematic review","volume":"13","author":"Xu","year":"2019","journal-title":"Prim. Care Diabetes"},{"key":"ref_39","first-page":"558","article-title":"Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF-1 levels, while improving height in patients small for gestational age A long-term observational study","volume":"96","author":"Villalobos","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e26711","DOI":"10.1097\/MD.0000000000026711","article-title":"Efficacy and safety of the recombinant human growth hormone in short children born small for gestational age","volume":"100","author":"Kim","year":"2021","journal-title":"Medicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1687-9856-2012-11","article-title":"Early diagnosis and treatment referral of children born small for gestational age without catch-up growth are critical for optimal growth outcomes","volume":"2012","author":"Houk","year":"2012","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000091719","article-title":"Safety of Growth Hormone Treatment in Children Born Small for Gestational Age: The US Trial and KIGS Analysis","volume":"65","author":"Cutfield","year":"2006","journal-title":"Horm. Res. Paediatr."},{"key":"ref_43","first-page":"391","article-title":"Estudio de la subunidad \u00e1cido-l\u00e1bil y su utilidad en pediatr\u00eda","volume":"115","author":"Zaidman","year":"2017","journal-title":"Arch. Argent. De Pediatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e1291","DOI":"10.1210\/clinem\/dgz118","article-title":"Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA","volume":"105","author":"Wegmann","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/13\/4392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:57Z","timestamp":1760126637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/13\/4392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,29]]},"references-count":44,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jcm12134392"],"URL":"https:\/\/doi.org\/10.3390\/jcm12134392","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,29]]}}}