{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:54:59Z","timestamp":1785477299400,"version":"3.56.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To assess a decade of growth hormone (GH) treatment patterns and outcomes in a real-world setting in Israel using a state-of-the-art computerized database.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This large retrospective database study included 2,379 children initiating GH treatment in Maccabi Healthcare Services (between January 2004 and December 2014). Good adherence with therapy (proportion of days covered &amp;gt;80%) was assessed during follow-up.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> At GH treatment initiation: 62.1% were boys; height standard deviation score (SDS) was \u22122.36 \u00b1 0.65 (mean \u00b1 SD); age was 9.8 \u00b1 3.1 years; and time from short stature diagnosis to first GH purchase was 4.8 \u00b1 3.3 years. Mean treatment period was 3.5 \u00b1 0.95 years; 79.4% of children were treated for more than 3 years. The two main indications for GH therapy were idiopathic short stature (ISS) (<jats:italic>n<\/jats:italic> = 1,615, 67.9%) and GH deficiency (GHD) (<jats:italic>n<\/jats:italic> = 611, 25.7%). Children in the highest socio-economic-status (SES) tertile comprised 61.3% of ISS and 59.7% of GHD. After 3 years, mean height gain SDS was 1.09 \u00b1 0.91 for GHD and 0.96 \u00b1 0.57 for ISS (<jats:italic>p<\/jats:italic> = 0.0004). Adult height (age 15 for girls and 17 for boys) was recorded for 624 patients (26.2%) with better outcomes for GHD than ISS (\u22121.0\u00b10.82 vs. \u22121.28\u00b10.93, respectively; <jats:italic>p<\/jats:italic> = 0.0002). Good adherence was achieved in 78.2% of the cohort during the first year and declined thereafter to 68.1% during the third year of the treatment.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Children who initiate GH therapy are predominantly male, belong mainly to the upper SES, commence treatment a long period after initial recognition of short stature, and have suboptimal adherence. Appropriate referral, diagnosis, and follow-up care may result in better treatment outcomes with GH therapy.<\/jats:p>","DOI":"10.3389\/fped.2021.711979","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T14:49:38Z","timestamp":1629470978000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Real-World Treatment Patterns and Outcomes of Growth Hormone Treatment Among Children in Israel Over the Past Decade (2004\u20132015)"],"prefix":"10.3389","volume":"9","author":[{"given":"Tal","family":"Ben-Ari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Chodick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varda","family":"Shalev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalit","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohar","family":"Landau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1210\/jcem-18-8-901","article-title":"Treatment of a pituitary dwarf with human growth hormone","volume":"18","author":"Raben","year":"1958","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1136\/bmj.328.7445.907","article-title":"Growth hormone: uses and abuses","volume":"328","author":"Hintz","year":"2004","journal-title":"BMJ"},{"key":"B3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4274\/jcrpe.2017.S003","article-title":"The rationale for growth hormone therapy in children with short stature","volume":"9","author":"Deodati","year":"2017","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"B4","first-page":"1","article-title":"Growth hormone deficiency: an update","volume":"38","author":"Audi","year":"2013","journal-title":"Minerva Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1159\/000350829","article-title":"Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study","volume":"79","author":"Deal","year":"2013","journal-title":"Horm Res Paediatr"},{"key":"B6","doi-asserted-by":"publisher","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":"B7","doi-asserted-by":"publisher","first-page":"3990","DOI":"10.1210\/jc.85.11.3990","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. GH Research Society","volume":"85","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1159\/000350251","article-title":"Understanding the growth hormone therapy adherence paradigm: a systematic review","volume":"79","author":"Fisher","year":"2013","journal-title":"Horm Res Paediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1530\/EC-18-0135","article-title":"The metabolic outcomes of growth hormone treatment in children are gender specific","volume":"7","author":"Ciresi","year":"2018","journal-title":"Endocr Connect"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1210\/jc.2016-2962","article-title":"Growth hormone treatment in children with prader-willi syndrome: three years of longitudinal data in prepubertal children and adult height data from the KIGS database","volume":"102","author":"Bakker","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4730","DOI":"10.1210\/jc.2019-00775","article-title":"Treatment of children with GH in the United States and Europe: long-term follow-up from NordiNet(R) IOS and answer program","volume":"104","author":"Savendahl","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1136\/archdischild-2018-316262","article-title":"Growth hormone prescribing patterns in the UK, 2013\u20132016","volume":"104","author":"Shepherd","year":"2019","journal-title":"Arch Dis Child"},{"key":"B14","first-page":"702","article-title":"Issues and trends in pediatric growth hormone therapy\u2013an update from the GHMonitor observational registry","volume":"5","author":"Pitukcheewanont","year":"2008","journal-title":"Pediatr Endocrinol Rev"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e0208539","DOI":"10.1371\/journal.pone.0208539","article-title":"Adherence to quality of care measurements among 58,182 patients with new onset diabetes and its association with mortality","volume":"13","author":"Hemo","year":"2018","journal-title":"PLoS ONE"},{"key":"B16","volume-title":"Membership in Sick Funds","author":"Cohen","year":"2013"},{"key":"B17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/1471-0528.14711","article-title":"Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members","volume":"125","author":"Eisenberg","year":"2018","journal-title":"BJOG"},{"key":"B18","volume-title":"Characterization and Classification of Geographical Units by the Socioeconomic Level of the Population.","author":"Burck","year":"2000"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.2147\/PPA.S70019","article-title":"Maintaining persistence and adherence with subcutaneous growth-hormone therapy in children: comparing jet-delivery and needle-based devices","volume":"8","author":"Spoudeas","year":"2014","journal-title":"Patient Prefer Adherence"},{"key":"B20","first-page":"40","article-title":"Review of growth hormone randomized controlled trials in children with idiopathic short stature","volume-title":"Horm Res Paediatr","author":"Deodati","year":"2011"},{"key":"B21","doi-asserted-by":"publisher","first-page":"119","DOI":"10.2147\/CLEP.S42602","article-title":"The NordiNet(R) International Outcome Study and NovoNet(R) ANSWER Program(R): rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy (Norditropin(R))","volume":"5","author":"Hoybye","year":"2013","journal-title":"Clin Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1515\/jpem-2017-0489","article-title":"Still too little, too late? Ten years of growth hormone therapy baseline data from the NordiNet(R) International Outcome Study","volume":"31","author":"Polak","year":"2018","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1210\/jc.2005-2284","article-title":"Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database","volume":"91","author":"Reiter","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ghir.2018.10.004","article-title":"Long-term adherence to growth hormone therapy in a large health maintenance organization cohort","volume":"44","author":"Farfel","year":"2019","journal-title":"Growth Horm IGF Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1159\/000452887","article-title":"Baseline characteristics and gender differences in prepubertal children treated with growth hormone in Europe, USA, and Japan: 25 years' KIGS(R) experience (1987\u20132012) and review","volume":"87","author":"Ranke","year":"2017","journal-title":"Horm Res Paediatr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1001\/archpedi.156.3.230","article-title":"Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis","volume":"156","author":"Finkelstein","year":"2002","journal-title":"Arch Pediatr Adolesc Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1210\/js.2019-00246","article-title":"US growth hormone use in the idiopathic short stature era: trends in insurer payments and patient financial burden","volume":"3","author":"Grimberg","year":"2019","journal-title":"J Endocr Soc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ijpam.2016.07.002","article-title":"Diagnosis and management of growth disorders in Gulf Cooperation Council (GCC) countries: current procedures and key recommendations for best practice","volume":"3","author":"Al Herbish","year":"2016","journal-title":"Int J Pediatr Adolesc Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1159\/000098707","article-title":"Age at growth hormone therapy start and first-year responsiveness to growth hormone are major determinants of height outcome in idiopathic short stature","volume":"68","author":"Ranke","year":"2007","journal-title":"Horm Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"11099","DOI":"10.1038\/srep11099","article-title":"Gender bias in U.S. pediatric growth hormone treatment","volume":"5","author":"Grimberg","year":"2015","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1530\/EJE-16-1024","article-title":"Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet(R) International Outcome Study","volume":"177","author":"Polak","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1159\/000502901","article-title":"The challenge of defining and investigating the causes of idiopathic short stature and finding an effective therapy","volume":"92","author":"Inzaghi","year":"2019","journal-title":"Horm Res Paediatr"},{"key":"B33","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1159\/000053138","article-title":"Patient attitudes and preferences regarding treatment: GH therapy for childhood short stature","volume":"51","author":"Finkelstein","year":"1999","journal-title":"Horm Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1001\/jama.276.7.531","article-title":"Short stature and growth hormone therapy. A national study of physician recommendation patterns","volume":"276","author":"Cuttler","year":"1996","journal-title":"JAMA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1097\/MLR.0b013e31819e1f04","article-title":"Patient, physician, and consumer drivers: referrals for short stature and access to specialty drugs","volume":"47","author":"Cuttler","year":"2009","journal-title":"Med Care"},{"key":"B36","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1056\/NEJMra050100","article-title":"Adherence to medication","volume":"353","author":"Osterberg","year":"2005","journal-title":"N Engl J Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1136\/bmj.325.7355.70","article-title":"Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry","volume":"325","author":"Carel","year":"2002","journal-title":"BMJ"},{"key":"B38","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.clinthera.2008.02.017","article-title":"Observations of nonadherence to recombinant human growth hormone therapy in clinical practice","volume":"30","author":"Haverkamp","year":"2008","journal-title":"Clin Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.ghir.2011.09.004","article-title":"The benefits of growth hormone therapy in patients with Turner syndrome, Noonan syndrome and children born small for gestational age","volume":"21","author":"Kappelgaard","year":"2011","journal-title":"Growth Horm IGF Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1001\/jama.288.22.2880","article-title":"Helping patients follow prescribed treatment: clinical applications","volume":"288","author":"Haynes","year":"2002","journal-title":"JAMA"},{"key":"B41","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1001\/jama.288.4.462","article-title":"Adherence with statin therapy in elderly patients with and without acute coronary syndromes","volume":"288","author":"Jackevicius","year":"2002","journal-title":"JAMA"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.711979\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T14:49:44Z","timestamp":1629470984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.711979\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,20]]},"references-count":41,"alternative-id":["10.3389\/fped.2021.711979"],"URL":"https:\/\/doi.org\/10.3389\/fped.2021.711979","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,20]]},"article-number":"711979"}}