Dose Dependency of Iatrogenic Glucocorticoid Excess and Adrenal Insufficiency and Mortality: A Cohort Study in England
Open Access
- 22 April 2019
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 104 (9), 3757-3767
- https://doi.org/10.1210/jc.2019-00153
Abstract
Context Adrenal insufficiency and Cushing 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 A total of 70,638 oral glucocorticoid users and 41,166 nonusers aged ≥18 years registered in 389 practices in 1998 to 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 had glucocorticoid-induced Cushing syndrome. A total of 22,317 (31.6%) and 7544 (18.3%) deaths occurred among glucocorticoid users and nonusers, respectively. The incidence of all outcomes increased with higher current daily and cumulative doses. For adrenal insufficiency, the increases in HRs were 1.07 (95% CI: 1.04 to 1.09) for every increase of 5 mg per day and 2.25 (95% CI: 2.15 to 2.35) per 1000 mg of cumulative prednisolone-equivalent dose over the past year. The respective increases in HRs for Cushing syndrome were 1.09 (95% CI: 1.08 to 1.11) and 2.31 (95% CI: 2.23 to 2.40) and for mortality 1.26 (95% CI: 2.24 to 1.28) and 2.05 (95% CI: 2.04 to 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.Keywords
Funding Information
- Medical Research Council (RO-115-2018-1061)
- European Research Council (250271)
- National Institute for Health Research (RGRMEX 107713, MIC-2016-015, NF-SI-0514-10090)
This publication has 25 references indexed in Scilit:
- Understanding the side effects of glucocorticoid therapy: shining a light on a drug everyone thinks they knowAnnals Of The Rheumatic Diseases, 2012
- DAGittyEpidemiology, 2011
- Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 yearsRheumatology, 2011
- Multiple imputation using chained equations: Issues and guidance for practiceStatistics in Medicine, 2010
- Overadjustment Bias and Unnecessary Adjustment in Epidemiologic StudiesEpidemiology, 2009
- Imputing missing covariate values for the Cox modelStatistics in Medicine, 2009
- Dose-related patterns of glucocorticoid-induced side effectsAnnals Of The Rheumatic Diseases, 2008
- Impact of inhaled corticosteroids on cortisol suppression in adults with asthma: a quantitative reviewAnnals of Allergy, Asthma & Immunology, 2008
- Immortal Time Bias in PharmacoepidemiologyAmerican Journal of Epidemiology, 2007
- Estimating the Dimension of a ModelThe Annals of Statistics, 1978