Description:
<jats:title>Summary</jats:title><jats:sec><jats:title>Context</jats:title><jats:p>Long‐term 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‐<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‐specific mortality in childhood‐onset <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‐based 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>‐replaced patients and non‐<jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced 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>‐ and non‐<jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced 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> = 7·51 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content> = 6·06–9·31). Comparing <jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced patients with non‐<jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced patients mortality was significantly decreased in total (<jats:styled-content style="fixed-case">HR</jats:styled-content> = 0·27, <jats:styled-content style="fixed-case">CI</jats:styled-content> = 0·17–0·43) and due to malignancy (<jats:styled-content style="fixed-case">HR</jats:styled-content> = 0·14, <jats:styled-content style="fixed-case">CI</jats:styled-content> = 0·07–0·28) in <jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced patients. Adjusting for relevant confounders, this decrease remained significant both in total (<jats:styled-content style="fixed-case">HR</jats:styled-content> = 0·56, <jats:styled-content style="fixed-case">CI</jats:styled-content> = 0·32–0·96) and due to malignancy (<jats:styled-content style="fixed-case">HR</jats:styled-content> = 0·33, <jats:styled-content style="fixed-case">CI</jats:styled-content> = 0·16–0·69). Overall and cause‐specific mortality was increased in both <jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced and non‐<jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced patients compared to general population controls, but mortality was generally highest in non‐<jats:styled-content style="fixed-case">GH</jats:styled-content>‐replaced 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>