Mebrahtu, T orcid.org/0000-0003-4821-2304, Morgan, AW orcid.org/0000-0003-1109-624X, Keeley, A orcid.org/0000-0003-4396-0549 et al. (3 more authors) (2019) Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England. Journal of Clinical Endocrinology and Metabolism, 104 (9). jc.2019-00. pp. 3757-3767. ISSN 0021-972X
Abstract
Context: Adrenal insufficiency and Cushing’s syndrome are known adverse events of glucocorticoids. However, no population estimates of dose-related risks are available.
Objective: To investigate dose-related risks of adrenal dysfunction and death in adults with six chronic inflammatory diseases treated with oral glucocorticoids.
Design and setting: Retrospective record-linkage open-cohort study spanning primary and hospital care in England.
Patients: 70,638 people oral glucocorticoid-users and 41,166 non-users aged ≥18 years registered in 389 practices in 1998-2017.
Main outcome measures: Incidence rates and hazard ratios (HRs) of diagnosed adrenal dysfunction and death.
Results: During a median follow-up of 5.5 years, 183 patients had glucocorticoid-induced adrenal insufficiency and 248 glucocorticoid-induced Cushing’s syndrome. A total of 22,317 (31.6%) and 7,544 (18.3%) deaths occurred amongst glucocorticoid users and non-users, respectively. Incidence of all outcomes increased with higher current daily and cumulative doses. For adrenal insufficiency, the increases in HRs were of 1.07 (95% CI 1.04-1.09) for every increase of 5mg per day and of 2.25 (95% CI 2.15-2.35) per 1000mg of cumulative prednisolone-equivalent dose over the past year. The respective increases in HRs for Cushing’s syndrome were of 1.09 (95% CI 1.08-1.11) and 2.31 (95% CI 2.23-2.40) and for mortality of 1.26 (95% CI 2.24-1.28) and 2.05 (95% CI 2.04-2.06).
Conclusion: We report a high glucocorticoid dose-dependent increased risk of adrenal adverse events and death. The low observed absolute risk of adrenal insufficiency highlights a potential lack of awareness, and a need for increased physician and patient education about the risks of adrenal dysfunction induced by glucocorticoids.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). |
Keywords: | Adrenal dysfunction; adrenal insufficiency; cohort studies; Cushing's syndrome; glucocorticoids; mortality; toxicity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Healthcare (Leeds) > Nursing Adult (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Specialist Science Education Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Health Sciences (Leeds) > Centre for Health Services Research (Leeds) |
Funding Information: | Funder Grant number MRC MR/N011775/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Apr 2019 14:55 |
Last Modified: | 17 Dec 2024 12:45 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1210/jc.2019-00153 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145124 |