{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:33:06Z","timestamp":1787160786550,"version":"build-2736575974"},"reference-count":49,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess mortality in children receiving GH.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Prospective, multinational, observational study.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n Eight hundred twenty-seven study sites in 30 countries.<\/jats:p>\n <\/jats:sec>\n \n Patients<\/jats:title>\n Children with growth disorders.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n GH treatment during childhood.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measure<\/jats:title>\n Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 9504 GH-treated patients followed for \u22654 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non\u2013GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non\u2013GH-deficient medical conditions.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/jc.2017-00214","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T14:04:41Z","timestamp":1495807481000},"page":"3195-3205","source":"Crossref","is-referenced-by-count":31,"title":["Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study"],"prefix":"10.1210","volume":"102","author":[{"given":"Charmian A","family":"Quigley","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Child","sequence":"additional","affiliation":[{"name":"Endocrinology, Lilly Research Laboratories, Windlesham, Surrey GU20 6PH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan G","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Statistics, Lilly Research Laboratories, Indianapolis, Indiana 46285"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron G","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie L","family":"Robison","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner F","family":"Blum","sequence":"additional","affiliation":[{"name":"Endocrinology, University Children\u2019s Hospital, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2017,5,26]]},"reference":[{"issue":"1","key":"2020071619395254600_B1","first-page":"1","article-title":"Growth hormone deficiency: an update","volume":"38","author":"Aud\u00ed","year":"2013","journal-title":"Minerva Endocrinol"},{"issue":"2","key":"2020071619395254600_B2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0022-3476(98)70452-4","article-title":"Growth hormone therapy of Turner\u2019s syndrome: beneficial effect on adult height","volume":"132","author":"Rosenfeld","year":"1998","journal-title":"J Pediatr"},{"issue":"6","key":"2020071619395254600_B3","doi-asserted-by":"crossref","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"},{"issue":"8","key":"2020071619395254600_B4","doi-asserted-by":"crossref","first-page":"E1383","DOI":"10.1210\/jc.2013-1222","article-title":"GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial","volume":"98","author":"Blum","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2020071619395254600_B5","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/jmg.2006.046581","article-title":"Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency","volume":"44","author":"Rappold","year":"2007","journal-title":"J Med Genet"},{"issue":"1","key":"2020071619395254600_B6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/jc.2006-1409","article-title":"Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: two-year results of a randomized, controlled, multicenter trial","volume":"92","author":"Blum","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2020071619395254600_B7","doi-asserted-by":"crossref","first-page":"E1072","DOI":"10.1210\/jc.2012-3888","article-title":"GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome","volume":"98","author":"Deal","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2020071619395254600_B8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1210\/jc.2009-0178","article-title":"Long-term safety of recombinant human growth hormone in children","volume":"95","author":"Bell","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2020071619395254600_B9","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1054\/ghir.2000.0175","article-title":"Safety issues in children and adolescents during growth hormone therapy--a review","volume":"10","author":"Clayton","year":"2000","journal-title":"Growth Horm IGF Res"},{"issue":"2","key":"2020071619395254600_B10","doi-asserted-by":"crossref","first-page":"P1","DOI":"10.1530\/EJE-15-0873","article-title":"GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults","volume":"174","author":"Allen","year":"2016","journal-title":"Eur J Endocrinol"},{"issue":"7","key":"2020071619395254600_B11","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1210\/jcem.87.7.8606","article-title":"Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study","volume":"87","author":"Sklar","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2020071619395254600_B12","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.1210\/jc.2006-0656","article-title":"Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor","volume":"91","author":"Ergun-Longmire","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2020071619395254600_B13","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1212\/WNL.0000000000000737","article-title":"Growth hormone treatment for childhood short stature and risk of stroke in early adulthood","volume":"83","author":"Poidvin","year":"2014","journal-title":"Neurology"},{"issue":"2","key":"2020071619395254600_B14","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1210\/jc.2011-1995","article-title":"Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study","volume":"97","author":"Carel","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2020071619395254600_B15","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1210\/jc.2015-1002","article-title":"Risk of neoplasia in pediatric patients receiving growth hormone therapy--a report from the Pediatric Endocrine Society Drug and Therapeutics Committee","volume":"100","author":"Raman","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2020071619395254600_B16","doi-asserted-by":"crossref","first-page":"E213","DOI":"10.1210\/jc.2011-2882","article-title":"Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study","volume":"97","author":"S\u00e4vendahl","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071619395254600_B17","unstructured":"Surveillance, Epidemiology, and End Results Program, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. SEER*Stat Database: Incidence\u2014SEER 13 Regs Research Data, Nov 2013 Sub (1992-2011) (Katrina\/Rita Population Adjustment). Available at: https:\/\/seer.cancer.gov\/data\/seerstat\/nov2013. Accessed 28 November 2016."},{"issue":"2","key":"2020071619395254600_B18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00401-007-0243-4","article-title":"The 2007 WHO classification of tumours of the central nervous system","volume":"114","author":"Louis","year":"2007","journal-title":"Acta Neuropathol"},{"issue":"1","key":"2020071619395254600_B19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1542\/peds.109.1.45","article-title":"Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version","volume":"109","author":"Ogden","year":"2002","journal-title":"Pediatrics"},{"issue":"12","key":"2020071619395254600_B20","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/sj.ejcn.1601473","article-title":"A chart to link child centiles of body mass index, weight and height","volume":"56","author":"Cole","year":"2002","journal-title":"Eur J Clin Nutr"},{"key":"2020071619395254600_B21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1297\/cpe.2.87","article-title":"Standard growth charts for height and weight of Japanese children from birth to 17 years based on a cross-sectional survey of national data","volume":"2","author":"Suwa","year":"1993","journal-title":"Clin Pediatr Endocrinol"},{"issue":"5","key":"2020071619395254600_B22","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1210\/jc.2016-2046","article-title":"Cancer risks in patients treated with growth hormone in childhood: the SAGhE European cohort study","volume":"102","author":"Swerdlow","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2020071619395254600_B23","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/cen.12848","article-title":"Growth hormone replacement does not increase mortality in patients with childhood-onset growth hormone deficiency","volume":"83","author":"Berglund","year":"2015","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"14","key":"2020071619395254600_B24","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1093\/jnci\/djq238","article-title":"Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study","volume":"102","author":"Friedman","year":"2010","journal-title":"J Natl Cancer Inst"},{"issue":"6","key":"2020071619395254600_B25","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1210\/jc.2013-4159","article-title":"Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study","volume":"99","author":"Patterson","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2020071619395254600_B26","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/pbc.24427","article-title":"Children\u2019s Oncology Group\u2019s 2013 blueprint for research: central nervous system tumors","volume":"60","author":"Gajjar","year":"2013","journal-title":"Pediatr Blood Cancer"},{"issue":"9","key":"2020071619395254600_B27","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1515\/jpem.2010.150","article-title":"Growth hormone therapy and the risk of tumor recurrence after brain tumor treatment in children","volume":"23","author":"Rohrer","year":"2010","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"2","key":"2020071619395254600_B28","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1200\/JCO.2001.19.2.480","article-title":"Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control","volume":"19","author":"Packer","year":"2001","journal-title":"J Clin Oncol"},{"issue":"5 Pt 2","key":"2020071619395254600_B29","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/S0022-3476(96)70002-1","article-title":"Brain tumor recurrence in children treated with growth hormone: the National Cooperative Growth Study experience","volume":"128","author":"Moshang","year":"1996","journal-title":"J Pediatr"},{"issue":"10","key":"2020071619395254600_B30","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1080\/08035250600577889","article-title":"Recurrence of brain tumours in patients treated with growth hormone: analysis of KIGS (Pfizer International Growth Database)","volume":"95","author":"Darendeliler","year":"2006","journal-title":"Acta Paediatr"},{"issue":"21","key":"2020071619395254600_B31","doi-asserted-by":"crossref","first-page":"4726","DOI":"10.1200\/JCO.2005.00.760","article-title":"Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study","volume":"23","author":"Oyharcabal-Bourden","year":"2005","journal-title":"J Clin Oncol"},{"issue":"4","key":"2020071619395254600_B32","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1530\/EJE-12-0967","article-title":"Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS","volume":"168","author":"Woodmansee","year":"2013","journal-title":"Eur J Endocrinol"},{"issue":"21","key":"2020071619395254600_B33","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1093\/jnci\/djj411","article-title":"New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study","volume":"98","author":"Neglia","year":"2006","journal-title":"J Natl Cancer Inst"},{"key":"2020071619395254600_B34","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.biochi.2013.11.023","article-title":"Pathophysiology of X-linked adrenoleukodystrophy","volume":"98","author":"Berger","year":"2014","journal-title":"Biochimie"},{"issue":"22","key":"2020071619395254600_B35","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1161\/CIRCULATIONAHA.110.947002","article-title":"Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006","volume":"122","author":"Gilboa","year":"2010","journal-title":"Circulation"},{"issue":"1","key":"2020071619395254600_B36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.yapd.2012.04.006","article-title":"Medical update for children with Down syndrome for the pediatrician and family practitioner","volume":"59","author":"Hickey","year":"2012","journal-title":"Adv Pediatr"},{"issue":"2","key":"2020071619395254600_B37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/00062752-199903000-00005","article-title":"The molecular and cellular biology of Fanconi anemia","volume":"6","author":"Garcia-Higuera","year":"1999","journal-title":"Curr Opin Hematol"},{"issue":"7","key":"2020071619395254600_B38","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1177\/0961203315627202","article-title":"Overall and cause-specific mortality in systemic lupus erythematosus: an updated meta-analysis","volume":"25","author":"Lee","year":"2016","journal-title":"Lupus"},{"issue":"2","key":"2020071619395254600_B39","first-page":"121","article-title":"Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients","volume":"31","author":"Passamano","year":"2012","journal-title":"Acta Myol"},{"issue":"3","key":"2020071619395254600_B40","doi-asserted-by":"crossref","first-page":"R93","DOI":"10.1530\/JME-10-0133","article-title":"Novel mutations associated with combined pituitary hormone deficiency","volume":"46","author":"Romero","year":"2011","journal-title":"J Mol Endocrinol"},{"issue":"11","key":"2020071619395254600_B41","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1210\/jc.2014-2476","article-title":"Central hypoadrenalism","volume":"99","author":"Crowley","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2020071619395254600_B42","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1210\/jc.2008-1049","article-title":"Mortality in women with turner syndrome in Great Britain: a national cohort study","volume":"93","author":"Schoemaker","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071619395254600_B43","doi-asserted-by":"crossref","first-page":"642853","DOI":"10.1155\/2013\/642853","article-title":"Ewing sarcoma protein: a key player in human cancer","volume":"2013","author":"Paronetto","year":"2013","journal-title":"Int J Cell Biol"},{"issue":"12","key":"2020071619395254600_B44","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1136\/jmg.2007.052019","article-title":"Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature","volume":"44","author":"Carlson","year":"2007","journal-title":"J Med Genet"},{"issue":"2","key":"2020071619395254600_B45","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1210\/jc.2007-1723","article-title":"Long-term safety of recombinant human growth hormone in turner syndrome","volume":"93","author":"Bolar","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2020071619395254600_B46","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/bdra.20696","article-title":"Mortality among infants with birth defects: joint effects of size at birth, gestational age, and maternal race\/ethnicity","volume":"88","author":"Nembhard","year":"2010","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"issue":"5","key":"2020071619395254600_B47","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1210\/jc.2015-3951","article-title":"Mortality is not increased in recombinant human growth hormone-treated patients when adjusting for birth characteristics","volume":"101","author":"Albertsson-Wikland","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2020071619395254600_B48","doi-asserted-by":"crossref","first-page":"E1025","DOI":"10.1210\/jc.2010-3023","article-title":"Prevalence and incidence of diabetes mellitus in GH-treated children and adolescents: analysis from the GeNeSIS observational research program","volume":"96","author":"Child","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"9204","key":"2020071619395254600_B49","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/S0140-6736(99)04055-6","article-title":"Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment","volume":"355","author":"Cutfield","year":"2000","journal-title":"Lancet"}],"container-title":["The Journal of Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/102\/9\/3195\/19703355\/jc.2017-00214.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/102\/9\/3195\/19703355\/jc.2017-00214.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:40:28Z","timestamp":1594946428000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/102\/9\/3195\/3852682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,26]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2017-00214","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,9,1]]},"published":{"date-parts":[[2017,5,26]]}}}