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Mortality risk in patients with adrenal insufficiency using prednisolone or hydrocortisone: a retrospective cohort study

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Title: Mortality risk in patients with adrenal insufficiency using prednisolone or hydrocortisone: a retrospective cohort study
Authors: Ngaosuwan, K
Johnston, DG
Godsland, IF
Cox, J
Majeed, A
Quint, JK
Oliver, N
Robinson, S
Item 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.
Issue Date: 1-Aug-2021
Date of Acceptance: 4-May-2021
URI: http://hdl.handle.net/10044/1/91938
DOI: 10.1210/clinem/dgab347
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
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
adrenal failure
replacement therapy
adrenal failure
replacement therapy
adrenal failure
replacement therapy
Endocrinology & Metabolism
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Publication Status: Published
Conference Place: United States
Online Publication Date: 2021-05-16
Appears in Collections:Department of Metabolism, Digestion and Reproduction
National Heart and Lung Institute
School of Public Health