Mortality risk and causes of death in exogenous Cushing's syndrome: a systematic review and meta-analysis
Authors' conclusion
Chronic oral GC exposure was associated with increased mortality across disease groups, with higher cumulative and early-treatment doses correlating with higher risk. However, causal attribution remains uncertain due to confounding by indication, limited disease-severity data, and exposure misclassification. These findings support GC stewardship and targeted cardiovascular and infection risk mitigation, rather than indiscriminate dose reduction.
Study context
- Population
- Adults receiving chronic oral glucocorticoids (GCs); studies searched 1945 to March 2019
- Participants
- 51,380 adults116 studies128 cohorts
- Comparison
- Chronic oral GC exposure vs general population
- Outcome
- Overall mortality associated with chronic oral GC exposure (SMR)
Methodological detailsPRISMA, random-effects meta-analysis, mixed-effects meta-regression
- PRISMA
- Random-effects meta-analysis
- Mixed-effects meta-regression
Pooled result
As reported in the abstract
Overall mortality
Pooled SMR
1.87
95% CI 1.32–2.61; I2 74.0%
Pooled proportion of death
12.0%
95% CI 10–14%
Further pooled results
Mortality by disease group
- Inflammatory diseases
- 30.0%
- Vasculitides
- 18.0%
Dose-response
- Higher cumulative dose (≥5 g prednisolone-equivalent), average daily dose >5 mg/day and higher initial dose each independently associated with increased mortality
Causes of death
- CVD
- 25.6%
- Malignancy
- 15.7%
- Infection
- 13.4%
Original publication
Mortality risk and causes of death in exogenous Cushing's syndrome: a systematic review and meta-analysis. J Clin Endocrinol Metab. Published 24 March 2026. doi:10.
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