title: Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma.
abstract: BACKGROUND
  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).
  
  
  METHODS
  This was a follow-up study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. o.m.dekkers@lumc.nl
authors.forename: O M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: N R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: A M
authors.initials: AM
authors.lastname: Pereira
authors.forename: F
authors.initials: F
authors.lastname: Roelfsema
authors.forename: M O
authors.initials: MO
authors.lastname: van Aken
authors.forename: J H C
authors.initials: JH
authors.lastname: Voormolen
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
mesh_terms: D000236:Adenoma / Q000401:mortality* / Q000628:therapy; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000401:mortality* / Q000628:therapy; D010911:Pituitary Neoplasms / Q000401:mortality* / Q000628:therapy; D016019:Survival Analysis; D016896:Treatment Outcome