Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England.

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.

SUBMITTER: Mebrahtu TF 

PROVIDER: S-EPMC6656418 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature