{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:42:14Z","timestamp":1792622534601,"version":"4.5.0"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pediatric growth hormone deficiency requires dynamic testing for accurate\ndiagnosis because of the pulsatile secretion of growth hormone. The insulin\ntolerance test (ITT) is regarded as one of the most robust individual\nprovocative tests for growth hormone deficiency, although the broader pediatric\ndiagnostic standard requires a composite of auxological, clinical, and\nbiochemical criteria together with an inadequate response to two independent\nstimulation tests, except in specific high-probability contexts; insulin-like\ngrowth factor-1 (IGF-1) alone has limited diagnostic accuracy. This study\nevaluated whether combining low IGF-1 levels with a single failed ITT could\nimprove diagnostic efficiency for pediatric growth hormone deficiency. We\nconducted a retrospective cohort study of 214 children with short stature (aged\n2\u201316 y) evaluated at King Chulalongkorn Memorial Hospital between August 2019\nand January 2025. Growth hormone deficiency was confirmed in 63 patients using\ntwo growth hormone stimulation tests (peak growth hormone level: &lt;\u20097 ng\/mL).\nIGF-1 levels were expressed as standard deviation scores and analyzed at cutoff\nvalues of \u2264\u2009\u20131, \u20131.5, \u20132, and \u20132.5 in combination with failed ITT results.\nDiagnostic performance indices were calculated at each predefined cutoff\/test\ncombination, including sensitivity, specificity, positive predictive values,\nnegative predictive values, area under the receiver operating characteristic\ncurve, odds ratios, and accuracy. An IGF-1 standard deviation score of \u2264\u2009\u20132.5\ncombined with a single failed ITT showed a sensitivity of 38.6% and a\nspecificity of 92.6%, with a positive predictive value and a negative predictive\nvalue of 73.9% and 73.5%, respectively (p&lt;0.001). Because the\nreference standard for the growth hormone deficiency required failure of two\nstimulation tests, one of which was the ITT, we assessed this circularity\ndirectly: among 100 patients with both the ITT and clonidine results, findings\nwere discordant in 37 (exact McNemar p=0.008), and IGF-1 standard\ndeviation scores did not differ significantly across concordant and discordant\nsubgroups (Kruskal\u2013Wallis p=0.407). An IGF-1 standard deviation score\ncutoff of \u2264\u2009\u20132.5 combined with a single failed ITT identifies a subgroup of\nchildren at higher probability of growth hormone deficiency who may be\nprioritized for confirmatory evaluation. Given the modest sensitivity and\npositive predictive values of this criterion and the circularity inherent in a\nreference standard that itself incorporates the ITT, these findings should be\nregarded as hypothesis-generating rather than as a basis for changing current\ndiagnostic practice, which continues to require two independent stimulation\ntests except in specific high-probability contexts; prospective, multicenter\nvalidation is required.<\/jats:p>","DOI":"10.1055\/a-2930-3751","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:52:08Z","timestamp":1786747928000},"page":"399-405","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Low Insulin-Like Growth Factor-1 Levels and a Single Insulin Tolerance Test in Diagnosing Growth Hormone Deficiency"],"prefix":"10.1055","volume":"58","author":[{"given":"Chayanit","family":"Yuenyong","sequence":"additional","affiliation":[{"name":"Chulalongkorn University, Thailand","place":["Bangkok"],"department":["Division of Pediatric Endocrinology, Department of Pediatrics, Faculty\nof Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worapimon","family":"Lerdrassameethad","sequence":"additional","affiliation":[{"name":"Chulalongkorn University, Thailand","place":["Bangkok"],"department":["Division of Pediatric Endocrinology, Department of Pediatrics, Faculty\nof Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khomsak","family":"Srilanchakon","sequence":"additional","affiliation":[{"name":"Chulalongkorn University, Thailand","place":["Bangkok"],"department":["Division of Pediatric Endocrinology, Department of Pediatrics, Faculty\nof Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"06","key":"ref1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1210\/jc.2011-0179","article-title":"Evaluation and treatment of adult growth hormone deficiency: An Endocrine\nSociety clinical practice guideline","volume":"96","author":"M E Molitch","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"ref2","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.4158\/GL-2019-0405","article-title":"American Association of Clinical Endocrinologists and American College of\nEndocrinology guidelines for management of growth hormone deficiency in adults\nand patients transitioning from pediatric to adult care","volume":"25","author":"KC J Yuen","year":"2019","journal-title":"Endocr Pract"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/EP.15.S2.1","article-title":"American Association of Clinical Endocrinologists medical guidelines for\nclinical practice for growth hormone use in growth hormone-deficient adults and\ntransition patients - 2009 update","volume":"15","author":"D M Cook","year":"2009","journal-title":"Endocr Pract"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1172\/JCI113450","article-title":"Fasting enhances growth hormone secretion and amplifies the complex rhythms of\ngrowth hormone secretion in man","volume":"81","author":"K Y Ho","year":"1988","journal-title":"J Clin Invest"},{"issue":"06","key":"ref5","first-page":"1441","article-title":"A quantitative estimation of growth hormone secretion in normal man:\nReproducibility and relation to sleep and time of day","volume":"74","author":"E Van Cauter","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"issue":"02","key":"ref6","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1210\/jcem.87.2.8216","article-title":"Which patients do not require a GH stimulation test for the diagnosis of adult\nGH deficiency?","volume":"87","author":"M L Hartman","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"ref7","first-page":"3990","article-title":"Consensus guidelines for the diagnosis and treatment of growth hormone (GH)\ndeficiency in childhood and adolescence: Summary statement of the GH Research\nSociety","volume":"85","author":"Growth Hormone Research Society","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"issue":"03","key":"ref8","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/bjs.1800560315","article-title":"The adrenocortical response to surgery and insulin-induced hypoglycaemia in\ncorticosteroid-treated and normal subjects","volume":"56","author":"F S Plumpton","year":"1969","journal-title":"Br J Surg"},{"issue":"6836","key":"ref9","first-page":"1176","article-title":"Hazards of pharmacological tests of growth hormone secretion in childhood","volume":"304","author":"A Shah","year":"1992","journal-title":"BMJ."},{"issue":"05","key":"ref10","first-page":"1615","article-title":"Comparison between insulin-induced hypoglycemia and growth hormone-releasing\nhormone+arginine as provocative tests for the diagnosis of growth hormone\ndeficiency in adults","volume":"83","author":"G Aimaretti","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"issue":"08","key":"ref11","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1210\/jc.2018-00665","article-title":"Macimorelin as a diagnostic test for adult GH deficiency","volume":"103","author":"J M Garcia","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"issue":"04","key":"ref12","first-page":"187","article-title":"New diagnostic approaches for adult growth hormone deficiency","volume":"26","author":"N A Tritos","year":"2019","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"issue":"04","key":"ref13","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\ninsulin-like growth factor assays","volume":"57","author":"D R Clemmons","year":"2011","journal-title":"Clin Chem"},{"issue":"06","key":"ref14","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\nintrinsic bioactivities","volume":"278","author":"R C Baxter","year":"2000","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"05","key":"ref15","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1210\/jc.2013-3060","article-title":"Age- and sex-specific reference intervals across life span for insulin-like\ngrowth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio\nmeasured by new automated chemiluminescence assays","volume":"99","author":"N Friedrich","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"03","key":"ref16","first-page":"744","article-title":"Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and\nadults: Relation to age, sex, stage of puberty, testicular size, and body mass\nindex","volume":"78","author":"A Juul","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/MED.0b013e32834ec952","article-title":"Diagnosis of growth hormone deficiency in childhood","volume":"19","author":"T Stanley","year":"2012","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"issue":"09","key":"ref18","first-page":"3419","article-title":"Diagnostic value for growth hormone (GH) deficiency of insulin-like growth\nfactor I, insulin-like growth factor binding protein-3, and GH-releasing\nhormone-arginine test","volume":"83","author":"G Aimaretti","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"issue":"06","key":"ref19","first-page":"E1020","article-title":"Effect of growth hormone therapy on glucose homeostasis in children with GH\ndeficiency: A multicenter, prospective, observational study","volume":"96","author":"S Loche","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"04","key":"ref20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S1096-6374(03)00038-8","article-title":"Serum levels of insulin-like growth factor I and its binding proteins in health\nand disease","volume":"13","author":"A Juul","year":"2003","journal-title":"Growth Horm IGF Res"},{"issue":"09","key":"ref21","first-page":"3263","article-title":"Evaluation of the insulin tolerance test in the diagnosis of growth hormone\ndeficiency in children and adolescents","volume":"84","author":"M Maghnie","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"issue":"02","key":"ref22","first-page":"709","article-title":"Clinical review: Practical aspects in the management of adult growth hormone\ndeficiency","volume":"94","author":"K C Yuen","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"issue":"06","key":"ref23","first-page":"933","article-title":"Factors influencing the insulin tolerance test: Reliability and safety","volume":"160","author":"M Klose","year":"2009","journal-title":"Eur J Endocrinol"},{"issue":"12","key":"ref24","first-page":"494","article-title":"Guidelines for growth hormone and insulin-like growth factor-I treatment in\nchildren and adolescents: Growth Hormone Research Society and Pediatric\nEndocrine Society consensus","volume":"101","author":"A Grimberg","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jpeds.2014.02.027","article-title":"Etiologies and early diagnosis of short stature and growth failure in children\nand adolescents","volume":"164","author":"A D Rogol","year":"2014","journal-title":"J Pediatr"},{"issue":"12","key":"ref26","first-page":"1371","article-title":"Diagnostic value of insulin-like growth factor-1 and insulin-like growth factor\nbinding protein-3 in growth hormone deficiency: A systematic review and\nmeta-analysis","volume":"26","author":"Y Shen","year":"2020","journal-title":"Endocr Pract"},{"issue":"04","key":"ref27","first-page":"155","article-title":"Screening for growth hormone deficiency by serum IGF-I and IGFBP-3 measurements\nin children and adolescents","volume":"44","author":"G Binder","year":"1995","journal-title":"Horm Res"},{"issue":"08","key":"ref28","first-page":"1255","article-title":"Growth hormone treatment in children with GH deficiency and its effect on body\nmass index and fat distribution","volume":"17","author":"G Radetti","year":"2004","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref29","first-page":"626944","article-title":"Revisiting the diagnosis of GH deficiency in children","volume":"12","author":"E Inzaghi","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s11102-007-0035-9","article-title":"Normal levels of serum IGF-I: Determinants and validity of current reference\nranges","volume":"10","author":"G Brabant","year":"2007","journal-title":"Pituitary."},{"issue":"03","key":"ref31","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1210\/jc.2009-1471","article-title":"Observed and predicted growth responses in prepubertal children with growth\ndisorders: Guidance of growth hormone treatment by empirical variables","volume":"95","author":"M B Ranke","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref32","first-page":"37","article-title":"Growth hormone deficiency (GHD) in childhood and adolescence: Reappraisal","volume":"45","author":"M Maghnie","year":"1996","journal-title":"Horm Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"101698\ufeff","DOI":"10.1016\/j.ghir.2026.101698","article-title":"Low IGF-1 combined with a single clonidine stimulation test as a confirmatory\ntool for pediatric growth hormone deficiency","volume":"84","author":"K Srilanchakon","year":"2026","journal-title":"Growth Horm IGF Res"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2930-3751.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:37:13Z","timestamp":1792622233000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2930-3751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,21]]},"published-print":{"date-parts":[[2026,10]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2930-3751","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}