Mortality risk in patients with adrenal insufficiency using prednisolone or hydrocortisone: a retrospective cohort study
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
CONTEXT: Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due its longer duration of action and lower cost. OBJECTIVE: To determine mortality rates with prednisolone versus hydrocortisone. DESIGN: Observational study. SETTING: A UK primary care database (Clinical Practice Research Datalink). PARTICIPANTS: Patients with primary and secondary adrenal insufficiency, treated with either prednisolone or hydrocortisone, and controls individually matched for age, sex, period and place of follow-up. INTERVENTIONS: Nil. OUTCOMES: Mortality relative to individually matched controls. RESULTS: As expected, mortality in adrenal insufficiency irrespective of cause was increased, based on 5478 patients (4228 on hydrocortisone; 1250 on prednisolone) and 54314 controls (41934 and 12380, respectively). Overall, the adjusted hazard ratio (HR) was similar with the two treatments (prednisolone, 1.76 [95% CI, 1.54-2.01] vs. hydrocortisone 1.69 [1.57-1.82]; p=0.65). This was also the case for secondary adrenal insufficiency. In primary disease (1405 on hydrocortisone vs. 137 on prednisolone:13965 and 1347 controls, respectively), prednisolone-users were older, more likely to have another autoimmune disease and malignancy, and less likely to have mineralocorticoid replacement. Nevertheless, after adjustment, the HR for prednisolone-treated patients remained higher than for those taking hydrocortisone (2.92 [2.19-3.91] vs. 1.90 [1.66-2.16]; p=0.0020). CONCLUSIONS: In primary but not in secondary adrenal insufficiency mortality was higher with prednisolone. The study was large, but the number of prednisolone-treated patients was small, and they had greater risk factors. Nonetheless the increased mortality associated with prednisolone persisted despite statistical adjustment. Further evidence is needed regarding the long-term safety of prednisolone as routine replacement.
Date Issued
2021-08-01
Date Acceptance
2021-05-04
Citation
Journal of Clinical Endocrinology and Metabolism, 2021, 106 (8), pp.2242-2251
ISSN
0021-972X
Publisher
Endocrine Society
Start Page
2242
End Page
2251
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism
Volume
106
Issue
8
Copyright Statement
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This is a pre-copy-editing, author-produced version of an article accepted for publication in Journal of Clinical Endocrinology and Metabolism following peer review. The definitive publisher-authenticated version is available online at: https://academic.oup.com/jcem/article/106/8/2242/6276537
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33993277
PII: 6276537
Subjects
adrenal failure
glucocorticoids
replacement therapy
steroids
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-05-16