Abstract
ContextAdrenal insufficiency and Cushing syndrome are known adverse events of glucocorticoids. However, no population estimates of dose-related risks are available.ObjectiveTo investigate dose-related risks of adrenal dysfunction and death in adults with six chronic inflammatory diseases treated with oral glucocorticoids.Design and settingRetrospective, record-linkage, open-cohort study spanning primary and hospital care in England.PatientsA total of 70,638 oral glucocorticoid users and 41,166 nonusers aged ≥18 years registered in 389 practices in 1998 to 2017.Main outcome measuresIncidence rates and hazard ratios (HRs) of diagnosed adrenal dysfunction and death.ResultsDuring 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).ConclusionWe 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.
Highlights
Context: Adrenal insufficiency and Cushing syndrome are known adverse events of glucocorticoids
The increases in hazard ratio (HR) were 1.07 for every increase of 5 mg per day and 2.25 per 1000 mg of cumulative prednisolone-equivalent dose over the past year
The respective increases in HRs for Cushing syndrome were 1.09 and 2.31 and for mortality 1.26 and 2.05
Summary
Study population The study was conducted among patients registered in general practices of the Clinical Practice Research Datalink (CPRD) who had consented to data linkage between 1 January 1998 and 15 March 2017. Patient data from three linked data sources spanning primary and hospital care were used. Primary health care records from the CPRD [13] were used to identify diagnoses of diseases (e.g., adrenal insufficiency), prescribed medication, and results of laboratory tests. Hospital records from the Hospital Episode Statistics (www.hscic.gov.uk/hes) were used to identify diagnoses recorded during hospitalization. Data from the Office for National Statistics Codes used to identify patients with each of the chronic inflammatory diseases are shown in an online repository [15]
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