{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:32:16Z","timestamp":1787614336029,"version":"build-2736575974"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Growth Hormone & IGF Research"],"published-print":{"date-parts":[[2016,6]]},"DOI":"10.1016\/j.ghir.2015.11.005","type":"journal-article","created":{"date-parts":[[2015,11,30]],"date-time":"2015-11-30T02:17:38Z","timestamp":1448849858000},"page":"57-61","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":32,"special_numbering":"C","title":["Atypical defects resulting in growth hormone insensitivity"],"prefix":"10.1016","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1715-5020","authenticated-orcid":false,"given":"Jan M.","family":"Wit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"de Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ghir.2015.11.005_bb0005","first-page":"206","article-title":"Diagnostic approach in children with short stature","volume":"72","author":"Oostdijk","year":"2009","journal-title":"Horm. Res."},{"issue":"Suppl. 2","key":"10.1016\/j.ghir.2015.11.005_bb0010","first-page":"1","article-title":"ESPE classification of paediatric endocrine diagnoses","volume":"68","author":"Wit","year":"2007","journal-title":"Horm. Res."},{"key":"10.1016\/j.ghir.2015.11.005_bb0015","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1210\/jc.2008-0509","article-title":"Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the growth hormone research society, the lawson wilkins pediatric endocrine society, and the European society for paediatric endocrinology workshop","volume":"93","author":"Cohen","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0020","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ghir.2007.11.004","article-title":"Idiopathic short stature: definition, epidemiology, and diagnostic evaluation","volume":"18","author":"Wit","year":"2008","journal-title":"Growth Hormon. IGF Res."},{"key":"10.1016\/j.ghir.2015.11.005_bb0025","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/ncpendmet0195","article-title":"Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders","volume":"2","author":"Savage","year":"2006","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0030","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/GIM.0b013e3181a7e8f8","article-title":"ACMG practice guideline: genetic evaluation of short stature","volume":"11","author":"Seaver","year":"2009","journal-title":"Genet. Med."},{"key":"10.1016\/j.ghir.2015.11.005_bb0035","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1365-2265.2009.03775.x","article-title":"The continuum of growth hormone-IGF-I axis defects causing short stature: diagnostic and therapeutic challenges","volume":"72","author":"Savage","year":"2010","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.ghir.2015.11.005_bb0040","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.beem.2010.06.007","article-title":"Genetic evaluation of short stature","volume":"25","author":"Wit","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0045","doi-asserted-by":"crossref","DOI":"10.1159\/000338462","article-title":"Genetic analysis of short children with apparent growth hormone insensitivity","author":"Wit","year":"2012","journal-title":"Horm. Res. Paediatr."},{"key":"10.1016\/j.ghir.2015.11.005_bb0050","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1210\/endo.134.6.7515002","article-title":"Cellular localization and regulation of gene expression for components of the insulin-like growth factor ternary binding protein complex","volume":"134","author":"Chin","year":"1994","journal-title":"Endocrinology"},{"key":"10.1016\/j.ghir.2015.11.005_bb0055","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1359\/jbmr.2002.17.8.1408","article-title":"Localization and regulation of the growth hormone receptor and growth hormone-binding protein in the rat growth plate","volume":"17","author":"Gevers","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.ghir.2015.11.005_bb0060","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nrendo.2010.123","article-title":"The growth hormone receptor: mechanism of activation and clinical implications","volume":"6","author":"Brooks","year":"2010","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.ghir.2015.11.005_bb0065","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1074\/jbc.M113.523373","article-title":"Multimeric growth hormone receptor complexes serve as signaling platforms","volume":"289","author":"Sedek","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ghir.2015.11.005_bb0070","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1073\/pnas.86.20.8083","article-title":"Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism","volume":"86","author":"Godowski","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ghir.2015.11.005_bb0075","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1210\/er.2010-0023","article-title":"Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity","volume":"32","author":"David","year":"2011","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.ghir.2015.11.005_bb0080","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ymgme.2009.05.009","article-title":"The shortness of pygmies is associated with severe under-expression of the growth hormone receptor","volume":"98","author":"Bozzola","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0085","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s11154-007-9025-5","article-title":"Recent advances in growth hormone signaling","volume":"7","author":"Lanning","year":"2006","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"10.1016\/j.ghir.2015.11.005_bb0090","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1210\/me.2011-1211","article-title":"betaTrCP controls GH receptor degradation via two different motifs","volume":"26","author":"da Silva Almeida","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.ghir.2015.11.005_bb0095","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.1111\/j.1742-4658.2006.05347.x","article-title":"Growth hormone\/JAKSTAT axis signal-transduction defect. A novel treatable cause of growth failure","volume":"273","author":"Rojas-Gil","year":"2006","journal-title":"FEBS J."},{"key":"10.1016\/j.ghir.2015.11.005_bb0100","first-page":"897","article-title":"Increased growth hormone receptor (GHR) degradation due to over-expression of cytokine inducible SH2 domain-containing protein (CIS) as a cause of GH transduction defect (GHTD)","volume":"25","author":"Rojas-Gil","year":"2012","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0105","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.tem.2012.01.001","article-title":"Mapping the growth hormone\u2013Stat5b\u2013IGF-I transcriptional circuit","volume":"23","author":"Rotwein","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0110","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000343076","article-title":"Estradiol and pubertal growth in girls","volume":"78","author":"Albin","year":"2012","journal-title":"Horm. Res. Paediatr."},{"key":"10.1016\/j.ghir.2015.11.005_bb0115","article-title":"Growth hormone receptor gene expression in puberty","author":"Pagani","year":"2015","journal-title":"Horm. Metab. Res."},{"key":"10.1016\/j.ghir.2015.11.005_bb0120","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1074\/jbc.M109.043471","article-title":"Estrogen-mediated regulation of Igf1 transcription and uterine growth involves direct binding of estrogen receptor alpha to estrogen-responsive elements","volume":"285","author":"Hewitt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ghir.2015.11.005_bb0125","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3390\/nu7010517","article-title":"Nutritionally-induced catch-up growth","volume":"7","author":"Gat-Yablonski","year":"2015","journal-title":"Nutrients"},{"key":"10.1016\/j.ghir.2015.11.005_bb0130","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1210\/en.2011-1909","article-title":"Role of fibroblast growth factor 21 (FGF21) in undernutrition-related attenuation of growth in mice","volume":"153","author":"Kubicky","year":"2012","journal-title":"Endocrinology"},{"key":"10.1016\/j.ghir.2015.11.005_bb0135","doi-asserted-by":"crossref","first-page":"26060","DOI":"10.1074\/jbc.M112.343707","article-title":"Fibroblast growth factor 21 (FGF21) inhibits chondrocyte function and growth hormone action directly at the growth plate","volume":"287","author":"Wu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ghir.2015.11.005_bb0140","doi-asserted-by":"crossref","first-page":"27375","DOI":"10.1074\/jbc.M113.462218","volume":"288","author":"Wu","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ghir.2015.11.005_bb0145","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1159\/000367922","article-title":"Serum fibroblast growth factor 21 levels are inversely associated with growth rates in infancy","volume":"82","author":"Mericq","year":"2014","journal-title":"Horm. Res. Paediatr."},{"key":"10.1016\/j.ghir.2015.11.005_bb0150","doi-asserted-by":"crossref","first-page":"E2198","DOI":"10.1210\/jc.2014-1566","article-title":"Elevated FGF21 leads to attenuated postnatal linear growth in preterm infants through GH resistance in chondrocytes","volume":"99","author":"Guasti","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0155","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1007\/s10620-015-3571-6","article-title":"Interleukin (IL)-1 gene cluster in inflammatory bowel disease: is IL-1RA implicated in the disease onset and outcome?","volume":"60","author":"Muro","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"10.1016\/j.ghir.2015.11.005_bb0160","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/ibd.21689","article-title":"Innate dysfunction promotes linear growth failure in pediatric Crohn's disease and growth hormone resistance in murine ileitis","volume":"18","author":"D'Mello","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.ghir.2015.11.005_bb0165","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1753-4887.1999.tb06939.x","article-title":"Regulation of insulin-like growth factor-I in starvation and injury","volume":"57","author":"Thissen","year":"1999","journal-title":"Nutr. Rev."},{"key":"10.1016\/j.ghir.2015.11.005_bb0170","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1097\/01.CCM.0000215113.66070.E0","article-title":"Hepatic growth hormone resistance during sepsis is associated with increased suppressors of cytokine signaling expression and impaired growth hormone signaling","volume":"34","author":"Yumet","year":"2006","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.ghir.2015.11.005_bb0175","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0049374","article-title":"The Jak\/STAT signaling pathway is downregulated at febrile temperatures","volume":"7","author":"Nespital","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ghir.2015.11.005_bb0180","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/ki.2013.196","article-title":"Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation","volume":"84","author":"Troib","year":"2013","journal-title":"Kidney Int."},{"key":"10.1016\/j.ghir.2015.11.005_bb0185","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.beem.2010.09.003","article-title":"STAT5b deficiency: lessons from STAT5b gene mutations","volume":"25","author":"Hwa","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0190","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1073\/pnas.1119803109","article-title":"Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature","volume":"109","author":"De Rocca","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"Suppl. 2","key":"10.1016\/j.ghir.2015.11.005_bb0195","first-page":"64","article-title":"Noonan syndrome, the Ras-MAPK signalling pathway and short stature","volume":"71","author":"Binder","year":"2009","journal-title":"Horm. Res."},{"key":"10.1016\/j.ghir.2015.11.005_bb0200","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0049229","article-title":"Sotos syndrome is associated with deregulation of the MAPK\/ERK-signaling pathway","volume":"7","author":"Visser","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ghir.2015.11.005_bb0205","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1210\/me.2009-0178","article-title":"Growth hormone-activated STAT5 may indirectly stimulate IGF-I gene transcription through HNF-3{gamma}","volume":"23","author":"Eleswarapu","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.ghir.2015.11.005_bb0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.joca.2015.01.014","article-title":"Function of the chondrocyte PI-3 kinase-Akt signaling pathway is stimulus dependent","author":"Greene","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.ghir.2015.11.005_bb0215","doi-asserted-by":"crossref","first-page":"24726","DOI":"10.1074\/jbc.M110.175364","article-title":"Nuclear factor-kappaB (NF-kappaB) p65 interacts with Stat5b in growth plate chondrocytes and mediates the effects of growth hormone on chondrogenesis and on the expression of insulin-like growth factor-1 and bone morphogenetic protein-2","volume":"286","author":"Wu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ghir.2015.11.005_bb0220","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1084\/jem.20040773","article-title":"The same IkappaBalpha mutation in two related individuals leads to completely different clinical syndromes","volume":"200","author":"Janssen","year":"2004","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.ghir.2015.11.005_bb0225","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1210\/jc.2009-1662","article-title":"Growth hormone and insulin-like growth factor I insensitivity of fibroblasts isolated from a patient with an I{kappa}B{alpha} mutation","volume":"95","author":"Wu","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ghir.2015.11.005_bb0230","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1530\/EJE-11-0774","article-title":"A mosaic de novo duplication of 17q21-25 is associated with GH insensitivity, disturbed in vitro CD28-mediated signaling, and decreased STAT5B, PI3K, and NF-kappaB activation","volume":"166","author":"Mul","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.ghir.2015.11.005_bb0235","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1159\/000351958","article-title":"Adult and near-adult height in patients with severe insulin-like growth factor-I deficiency after long-term therapy with recombinant human insulin-like growth factor-I","volume":"80","author":"Backeljauw","year":"2013","journal-title":"Horm. Res. Paediatr."},{"issue":"Suppl. 1","key":"10.1016\/j.ghir.2015.11.005_bb0240","first-page":"55","article-title":"Effects of growth hormone treatment on growth in children with juvenile idiopathic arthritis","volume":"72","author":"Simon","year":"2009","journal-title":"Horm. Res."}],"container-title":["Growth Hormone & IGF Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S109663741530037X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S109663741530037X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T22:50:27Z","timestamp":1761087027000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S109663741530037X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":48,"alternative-id":["S109663741530037X"],"URL":"https:\/\/doi.org\/10.1016\/j.ghir.2015.11.005","relation":{},"ISSN":["1096-6374"],"issn-type":[{"value":"1096-6374","type":"print"}],"subject":[],"published":{"date-parts":[[2016,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Atypical defects resulting in growth hormone insensitivity","name":"articletitle","label":"Article Title"},{"value":"Growth Hormone & IGF Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ghir.2015.11.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2015 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}