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Mortality in Patients Treated for Cushing’s Disease Is Increased, Compared with Patients Treated for Nonfunctioning Pituitary Macroadenoma

Departments of Endocrinology and Metabolic Diseases (O.M.D., N.R.B., A.M.P., F.R., M.O.v.A., J.A.R.), Neurosurgery (J.H.C.V.), and Clinical Epidemiology (O.M.D.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: O. M. Dekkers, M.D., M.A., Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: o.m.dekkers{at}lumc.nl.

Context: Increased mortality in patients with pituitary tumors after surgical treatment has been reported. However, it is unknown to what extent excess mortality is caused by pituitary tumors and their treatment in general and to what extent by previous exposure to hormonal overproduction.

Objective: The aim of the study was to compare mortality between patients treated for Cushing’s disease and nonfunctioning pituitary macroadenomas (NFMAs).

Design: This was a follow-up study.

Patients: We included 248 consecutive patients with pituitary adenomas treated by transsphenoidal surgery in our hospital for NFMAs (n = 174) and ACTH-producing adenomas (n = 74). The mean duration of follow-up after surgery was 10.1 ± 7.2 yr for the whole cohort.

Outcome Measures: The standardized mortality ratio (SMR) was calculated for the whole cohort and also for the two diseases separately. Cox regression analysis was used to compare mortality in patients with Cushing’s disease with NFMA patients.

Results: Patients with Cushing’s disease (39.1 ± 16.1 yr) were significantly younger at time of operation than NFMA patients (55.3 ± 13.4 yr). The SMR for the whole cohort was 1.41 [95% confidence interval (CI), 1.05–1.86]. The SMR in NFMA patients was 1.24 (95% CI, 0.85–1.74) vs. 2.39 (95% CI, 1.22–3.9) in patients with Cushing’s disease. In patients with Cushing’s disease, compared with NFMAs, the age-adjusted mortality was significantly increased: hazard ratio 2.35 (95% CI, 1.13–4.09, P = 0.008).

Conclusions: Mortality in patients previously treated for Cushing’s disease is increased, compared with patients treated for NFMAs. This implies that previous, transient overexposure to cortisol is associated with increased mortality.

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