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Background: Patients with Cushing´s disease (CD) in remission have increased mortality compared to the general population. To date, large cohort studies, performed to assess long-term comorbidities in patients with CD, are lacking. Objective: To study the incidence of cardiovascular disease, sepsis, fractures and cancer in an unselected nationwide cohort of patients with CD. Methods: Patients with CD, diagnosed between 1987 and 2013, were identified in the Swedish National Patient Registry. Medical records were systematically reviewed to verify the diagnosis and remission status. Standardized incidence ratios (SIRs) for comorbidities after CD was diagnosed, with 95% confidence intervals (CI), were calculated by using the Swedish general population as the reference. Patients: A total of 502 patients had confirmed diagnosis of CD. Of these, 419 (83%) patients [325 (78%) women] were in remission at the last follow-up, and thereby eligible for the analysis. The mean±SD age at diagnosis was 41±15 years and median (interquartile range) time in remission was 10 years (4-21). Out of 419 patients in remission, 315 (75%) had been treated with pituitary surgery, 116 (28%) with radiotherapy and 102 (25%) with bilateral adrenalectomy. Results: SIR in patients in remission was 2.6 (1.9-3.4) for stroke, 1.8 (1.1-2.6) for myocardial infarction, 4.4 (2.5-7.1) for pulmonary embolism and 3.4 (1.8-6.0) for deep vein thrombosis. The risk for sepsis was markedly elevated with a SIR of 5.8 (3.8-8.4). SIR for all fractures was 1.7 (1.3-2.1), 2.6 (1.4-4.6) for wrist fracture and 1.6 (0.9-2.6) for hip fracture. The overall incidence of cancer was not increased [SIR 1.2 (0.9-1.5)] in comparison with the background population. Conclusions This large nationwide study shows that patients with CD in remission have an increased risk for cardiovascular disease, thromboembolism, fractures and severe infections. The excess morbidity in these patients illustrate the importance of early identification and management of risk factors for these comorbidities during long-term follow-up. |
