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Mortality Risk in Patients With Adrenal Insufficiency Using Prednisolone or Hydrocortisone: A Retrospective Cohort

Kanchana Ngaosuwan1,2, Desmond G Johnston1, Ian F Godsland1

  • 1Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College, London, UK.

The Journal of Clinical Endocrinology and Metabolism
|May 16, 2021
PubMed
Summary

Prednisolone may increase mortality in primary adrenal insufficiency compared to hydrocortisone, despite similar overall mortality rates. Further research is needed on long-term safety for this glucocorticoid replacement therapy.

Keywords:
adrenal failureglucocorticoidsreplacement therapysteroids

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Area of Science:

  • Endocrinology
  • Pharmacovigilance
  • Clinical Trials

Background:

  • Glucocorticoid replacement therapy is essential for adrenal insufficiency management.
  • Prednisolone is often recommended over hydrocortisone due to its longer action and lower cost.
  • Comparative safety and efficacy data, particularly regarding mortality, are crucial.

Purpose of the Study:

  • To compare mortality rates between patients treated with prednisolone and hydrocortisone for adrenal insufficiency.
  • To investigate potential differences in mortality risk based on the type of adrenal insufficiency (primary vs. secondary).

Main Methods:

  • Observational study using UK primary care database (Clinical Practice Research Datalink).
  • Matched cohort analysis comparing mortality in patients on prednisolone versus hydrocortisone.
  • Inclusion of control individuals matched for age, sex, and follow-up period.

Main Results:

  • Overall mortality was increased in adrenal insufficiency patients compared to controls, irrespective of glucocorticoid treatment.
  • No significant difference in adjusted mortality was observed between prednisolone and hydrocortisone for overall or secondary adrenal insufficiency.
  • In primary adrenal insufficiency, prednisolone users had higher adjusted mortality (HR 2.92) compared to hydrocortisone users (HR 1.90), despite greater risk factors in the prednisolone group.

Conclusions:

  • Prednisolone was associated with higher mortality in primary adrenal insufficiency, but not in secondary adrenal insufficiency.
  • Despite statistical adjustments, the increased mortality with prednisolone in primary disease persisted.
  • Further investigation into the long-term safety of prednisolone as a routine replacement therapy is warranted.