Prednisolone Vs Hydrocortisone Associated with Higher Mortality in Primary Adrenal Insufficiency

Pavankumar Kamat


May 24, 2021


  • The risk of mortality was significantly higher in patients with adrenal insufficiency compared with control participants, regardless of the glucocorticoid replacement agent.

  • Mortality risk relative to their matched control participants was higher in patients with primary adrenal insufficiency taking prednisolone vs hydrocortisone.

Why this matters

  • As prednisolone has a longer duration of action and is relatively cheaper, it is recommended as an alternative to hydrocortisone for patients with adrenal insufficiency.

  • However, mortality risk with the 2 glucocorticoid replacement agents needs investigation.

Study details

  • This retrospective study included 6821 patients with adrenal insufficiency (primary, n=2052; secondary, n=3948) from a UK primary care database treated with an oral glucocorticoid, i.e., hydrocortisone, cortisone acetate, prednisolone or prednisone.

  • Patients with adrenal insufficiency were matched 1:10 with age-, sex- and GP-matched control participants.

  • Funding: None.

Key results

  • Overall, 62% and 18% of patients with adrenal insufficiency were treated with hydrocortisone and prednisolone, respectively.

  • The risk of mortality was higher in patients receiving prednisolone (adjusted HR [aHR], 1.75; 95% CI, 1.53-2.00) or hydrocortisone (aHR, 1.70; 95% CI, 1.58-1.83) vs control participants.

  • In patients with primary adrenal insufficiency, prednisolone use was associated with higher mortality risk relative to control participants vs hydrocortisone (aHR, 2.87 vs 1.92; P=.004).

  • This difference was not observed in secondary adrenal insufficiency (P=.69).


  • The proportion of patients with primary adrenal insufficiency treated with prednisolone was small.

  • Cause of death and glucocorticoid dosages were not considered in the analysis.


Ngaosuwan K, Johnston DG, Godsland IF, Cox J, Majeed A, Quint JK, Oliver N, Robinson S. Full Mortality risk in patients with adrenal insufficiency using Prednisolone or Hydrocortisone: A Retrospective Cohort study. J Clin Endocrinol Metab. 2021 May 16 [Epub ahead of print]. doi: 10.1210/clinem/dgab347. PMID: 33993277.  View abstract 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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