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Excess Morbidity Persists in Patients With Cushing's Disease During Long-term Remission: A Swedish Nationwide Study
Eleni Papakokkinou1,2, Daniel S Olsson1,2, Dimitrios Chantzichristos1,2
1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
Patients with Cushing's disease (CD) face elevated risks of stroke, thromboembolism, and sepsis even after achieving remission. Long-term monitoring for these comorbidities is crucial for managing their health.
Area of Science:
- Endocrinology
- Internal Medicine
- Public Health
Background:
- Cushing's disease (CD) can lead to multisystem morbidity.
- The long-term health implications of CD during remission are not fully understood.
Purpose of the Study:
- To investigate the prevalence and incidence of comorbidities in patients with Cushing's disease.
- To assess if elevated morbidity persists during long-term remission of CD.
Main Methods:
- Retrospective nationwide study using the Swedish National Patient Register (1987-2013).
- Included 502 patients with confirmed CD, analyzing medical records for diagnosis and remission status.
- Calculated standardized incidence ratios (SIRs) comparing patients to the general population across different time periods: pre-diagnosis, diagnosis to 1-year post-remission, and long-term remission.
Main Results:
- Before diagnosis, patients showed increased SIRs for myocardial infarction, fractures, and deep vein thrombosis.
- From diagnosis to 1 year post-remission, elevated SIRs were observed for thromboembolism, stroke, and sepsis.
- During long-term remission, SIRs remained significantly increased for thromboembolism, stroke, and sepsis.
Conclusions:
- Cushing's disease patients experience a heightened risk of stroke, thromboembolism, and sepsis, persisting even after remission.
- These findings underscore the necessity of proactive risk factor management and continuous follow-up for these comorbidities in CD survivors.
Context:
Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.
Objective:
To investigate comorbidities in patients with CD.
Design, Setting, And Patients:
A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.
Main Outcomes:
Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.
Results:
We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.
Conclusion:
Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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