{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:29:56Z","timestamp":1785407396362,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"crossref","award":["503\/1-090-05\/503-11-001"],"award-info":[{"award-number":["503\/1-090-05\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"crossref"}]},{"award":["503\/1-090-05\/503-11-001"],"award-info":[{"award-number":["503\/1-090-05\/503-11-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case\u2013control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 \u00b5g\/L; additionally, a lower cut-off of 7.0 \u00b5g\/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 \u00b5g\/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p &lt; 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS &gt; 0.91. A Na\u00efve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients. Conclusions: Interpretation of GHST should include the patient\u2019s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children.<\/jats:p>","DOI":"10.3390\/jcm15093333","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:55:39Z","timestamp":1777370139000},"page":"3333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nutritional Status of Children with Short Stature Is Oppositely Associated with Growth Hormone Peak in Stimulation Tests and Insulin-like Growth Factor-1 Concentration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-9503","authenticated-orcid":false,"given":"Joanna","family":"Smyczy\u0144ska","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1399-457X","authenticated-orcid":false,"given":"Urszula","family":"Smyczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Hilczer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Polish Mother\u2019s Memorial Hospital\u2014Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0508-2186","authenticated-orcid":false,"given":"Renata","family":"Stawerska","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Polish Mother\u2019s Memorial Hospital\u2014Research Institute, 93-338 Lodz, Poland"},{"name":"Department of Developmental Age and Adult Endocrinology, Medical University of Lodz, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000452150","article-title":"Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency","volume":"86","author":"Grimberg","year":"2016","journal-title":"Horm. Res. Paediatr."},{"key":"ref_2","first-page":"1","article-title":"Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective","volume":"92","author":"Ambler","year":"2019","journal-title":"Horm. Res. Paediatr."},{"key":"ref_3","first-page":"1","article-title":"The ESPE classification of paediatric endocrine diagnoses","volume":"68","author":"Wit","year":"2007","journal-title":"Horm. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.4274\/jcrpe.galenos.2019.2019.0176","article-title":"A Proposal for the Interpretation of Serum IGF-I Concentration as Part of Laboratory Screening in Children with Growth Failure","volume":"12","author":"Wit","year":"2020","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1159\/000521281","article-title":"When Is a Positive Test for Pediatric Growth Hormone Deficiency a True-Positive Test?","volume":"94","author":"Bright","year":"2021","journal-title":"Horm. Res. Paediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1159\/000521628","article-title":"Diagnosis of Growth Hormone Deficiency Remains a Judgment Call\u2014And That Is Good","volume":"94","author":"Allen","year":"2021","journal-title":"Horm. Res. Paediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/archdischild-2014-307228","article-title":"Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence","volume":"101","author":"Murray","year":"2016","journal-title":"Arch. Dis. Child."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1515\/jpem-2021-0045","article-title":"Provocative growth hormone testing in children: How did we get here and where do we go now?","volume":"34","author":"Kamoun","year":"2021","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1159\/000526240","article-title":"The Influence of Body Mass Index on the Growth Hormone Peak Response regarding Growth Hormone Stimulation Tests in Children","volume":"95","author":"Thieme","year":"2022","journal-title":"Horm. Res. Paediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1210\/jc.2009-1369","article-title":"Effect of body mass index on peak growth hormone response to provocative testing in children with short stature","volume":"94","author":"Stanley","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16181","DOI":"10.1038\/s41598-019-52644-1","article-title":"Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency","volume":"9","author":"Yang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.5114\/pedm.2025.155108","article-title":"Auxological parameters associated with the diagnosis of growth hormone deficiency in children with short stature","volume":"31","author":"Hilczer","year":"2025","journal-title":"Pediatr. Endocrinol. Diabetes Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1365-2265.1987.tb01139.x","article-title":"Reduced growth hormone response to growth hormone-releasing hormone in children with simple obesity: Evidence for somatomedin-C mediated inhibition","volume":"27","author":"Loche","year":"1987","journal-title":"Clin. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1080\/10408363.2021.1956423","article-title":"Impact of body mass index on growth hormone stimulation tests in children and adolescents: A systematic review and meta-analysis","volume":"58","author":"Abawi","year":"2021","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_15","first-page":"17","article-title":"Indices of somatic development of children and adolescents in Warsaw","volume":"5","author":"Palczewska","year":"2001","journal-title":"Dev. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00431-010-1329-x","article-title":"Polish 2010 growth references for school-aged children and adolescents","volume":"170","author":"Litwin","year":"2011","journal-title":"Eur. J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00431-013-1954-2","article-title":"Polish 2012 growth references for preschool children","volume":"172","author":"Grajda","year":"2013","journal-title":"Eur. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1515\/CCLM.2004.112","article-title":"Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)","volume":"42","author":"Elmlinger","year":"2004","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ranke, M.B. (2003). Insulin-like growth factors and their binding proteins. Diagnostics of Endocrine Function in Children and Adolescents, Karger.","DOI":"10.1159\/isbn.978-3-318-00913-2"},{"key":"ref_20","unstructured":"Greulich, W.W., and Pyle, S.I. (1993). Radiographic Atlas of Skeletal Development of the Hand and Wrist, Stanford University Press. [2nd ed.]."},{"key":"ref_21","unstructured":"Siemens Healthcare Diagnostics Inc (2016). Introducing the Restandardized Insulin-Like Growth Factor-I (IGF-I) Assay. Cust. Bull., 5, 11222908."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00431-014-2406-3","article-title":"Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: A systematic review with meta-analysis","volume":"174","author":"Shen","year":"2015","journal-title":"Eur. J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ghir.2014.09.002","article-title":"The complex relationship between obesity and the somatropic axis: The long and winding road","volume":"24","author":"Savastano","year":"2014","journal-title":"Growth Horm. IGF Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2991","DOI":"10.1210\/clinem\/dgac157","article-title":"BMI and Contraceptives affect new age-, sex-, and puberty-adjusted IGF-I and IGFBP-3 reference ranges across life span","volume":"107","author":"Vogel","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"395","DOI":"10.26574\/maedica.2023.18.3.395","article-title":"IGF-1 Levels are dependent on age, but not weight status in children","volume":"18","author":"Negrea","year":"2023","journal-title":"Maedica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00431-022-04731-1","article-title":"Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease","volume":"182","author":"Haldrup","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3803\/EnM.2024.101","article-title":"The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin","volume":"39","author":"Berk","year":"2024","journal-title":"Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.5114\/pedm.2024.142590","article-title":"Does excessive body mass affect the rhGH therapy outcomes in GHD children?","volume":"30","author":"Maroszczuk","year":"2024","journal-title":"Pediatr. Endocrinol. Diabetes. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1007\/s12020-024-03984-0","article-title":"BMI z-score as a prognostic factor for height velocity in children treated with recombinant human growth hormone due to idiopathic growth hormone deficiency","volume":"86","author":"Budzulak","year":"2024","journal-title":"Endocrine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jped.2021.04.012","article-title":"Correlation of body mass index to Ghrelin and IGF-1 among children with short stature","volume":"98","author":"Amin","year":"2022","journal-title":"J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ghir.2014.10.006","article-title":"Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone\/insulin-like growth factor-1 status","volume":"25","author":"Savastano","year":"2015","journal-title":"Growth Horm. IGF Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1159\/000547492","article-title":"The Effect of Childhood Obesity on Growth: Interpretation of Growth Hormone Provocation Tests","volume":"99","author":"Karachaliou","year":"2026","journal-title":"Horm. Res. Paediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e220504","DOI":"10.1530\/EC-22-0504","article-title":"Diagnosis and testing for growth hormone deficiency across the ages: A global view of the accuracy, caveats, and cut-offs for diagnosis","volume":"12","author":"Yuen","year":"2023","journal-title":"Endocr. Connect."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ozdemir Dilek, S., and \u00d6zg\u00fc\u00e7 Comlek, F. (2026). Obesity-Related Changes in Growth Hormone Stimulation Test Performance Under Pediatric Growth Hormone Deficiency. Children, 13.","DOI":"10.3390\/children13020299"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1177\/00099228251335861","article-title":"The Crucial Role of Body Mass Index on Growth Hormone Stimulation Tests in Children: An Exploration of Potential Gender-Related Differences","volume":"64","author":"Ari","year":"2025","journal-title":"Clin. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhu, F., Wu, A., Chen, L., Xia, Y., Luo, X., Zhu, J., Huang, L., and Zhang, Y. (2025). Construction and evaluation of a height prediction model for children with growth disorders treated with recombinant human growth hormone. BMC Endocr. Disord., 25.","DOI":"10.1186\/s12902-025-01991-4"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1530\/EC-17-0277","article-title":"Pre-treatment growth and IGF-I deficiency as main predictors of response to growth hormone therapy in neural models","volume":"7","author":"Hilczer","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e54641","DOI":"10.2196\/54641","article-title":"Development and Validation of a Prediction Model Using Sella Magnetic Resonance Imaging-Based Radiomics and Clinical Parameters for the Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature: Cross-Sectional, Multicenter Study","volume":"26","author":"Song","year":"2024","journal-title":"J. Med. Internet Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Garner, T., Wangsaputra, I., Whatmore, A., Clayton, P.E., Stevens, A., and Murray, P.G. (2023). Diagnosis of childhood and adolescent growth hormone deficiency using transcriptomic data. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1026187"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/9\/3333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:18:08Z","timestamp":1778559488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/9\/3333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15093333"],"URL":"https:\/\/doi.org\/10.3390\/jcm15093333","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]}}}