{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:58:05Z","timestamp":1770487085587,"version":"3.49.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T00:00:00Z","timestamp":1438560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Long\u2010term safety of growth hormone (<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>) treatment is an area of much debate. Studies including children treated with <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> not only due to <jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content>, but also due to non\u2010<jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content> causes like idiopathic short stature or like short stature in children born small for gestational age have suggested that <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> treatment is associated with increased mortality or stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To study the impact of <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement on overall and cause\u2010specific mortality in childhood\u2010onset <jats:styled-content style=\"fixed-case\">GHD<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CO GHD<\/jats:styled-content>) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A nationwide population\u2010based registry study on patients with <jats:styled-content style=\"fixed-case\">CO GHD<\/jats:styled-content> and general population controls matched on age and gender. Mortality hazard ratios (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>s) were computed comparing patients and controls, and comparing <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients and non\u2010<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients, using <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ox regression. Comparing <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010 and non\u2010<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>s were adjusted for birth year, year of diagnosis, gender, irradiation, <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content> insufficiency and primary disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and controls<\/jats:title><jats:p>A total of 494 patients with <jats:styled-content style=\"fixed-case\">CO GHD<\/jats:styled-content> each matched with 100 general population controls were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mortality was substantially increased comparing patients with <jats:styled-content style=\"fixed-case\">CO GHD<\/jats:styled-content> and general population controls, <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a0=\u00a07\u00b751 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a06\u00b706\u20139\u00b731). Comparing <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients with non\u2010<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients mortality was significantly decreased in total (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a0=\u00a00\u00b727, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a00\u00b717\u20130\u00b743) and due to malignancy (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a0=\u00a00\u00b714, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a00\u00b707\u20130\u00b728) in <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients. Adjusting for relevant confounders, this decrease remained significant both in total (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a0=\u00a00\u00b756, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a00\u00b732\u20130\u00b796) and due to malignancy (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a0=\u00a00\u00b733, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a00\u00b716\u20130\u00b769). Overall and cause\u2010specific mortality was increased in both <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced and non\u2010<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients compared to general population controls, but mortality was generally highest in non\u2010<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>\u2010replaced patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present data from a national cohort of patients with <jats:styled-content style=\"fixed-case\">CO GHD<\/jats:styled-content> do not support the suggestion that <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> replacement is associated with increased mortality.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12848","type":"journal-article","created":{"date-parts":[[2015,7,4]],"date-time":"2015-07-04T13:12:48Z","timestamp":1436015568000},"page":"677-683","source":"Crossref","is-referenced-by-count":25,"title":["Growth hormone replacement does not increase mortality in patients with childhood\u2010onset growth hormone deficiency"],"prefix":"10.1111","volume":"83","author":[{"given":"Agnethe","family":"Berglund","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus H\u00f8jbjerg","family":"Gravholt","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital Denmark"},{"name":"Department of Molecular Medicine Aarhus University Hospital Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten 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