title: Mortality in Graves' orbitopathy is increased and influenced by gender, age and pre-existing morbidity: a nationwide Danish register study.
abstract: BACKGROUND
  It is unclear whether the excess mortality associated with Graves' disease differs between individuals with Graves' orbitopathy (GO) or without (GD).
  
  
  METHODS
  A nationwide, register-based cohort study in which all adult Danes diagnosed with GD (n= 28 461) and GO (n= 3965) between 1995 and 2012 were matched for age and gender with four control subjects. Median follow-up time was 7.9 years (range 0-17.5). Mortality risk in GO patients compared to the control population and compared to GD patients was calculated using Cox regression analyses, adjusting for pre-existing morbidity using the Charlson score.
  
  
  RESULTS
  Adjusted mortality in Graves' disease overall (GD + GO) was significantly increased compared to that in the background population (HR = 1.18 (95% confidence interval: 1.15-1.21)). In GD and GO separately, adjusted mortality was also significantly higher than that in their respective control populations (HR: 1.19 (1.16-1.22) and HR: 1.23 (1.12-1.35) respectively). However, mortality in GO compared to that in GD was decreased (HR: 0.64 (0.59-0.69)), although this difference attenuated after adjustment for pre-existing morbidity, age and gender. Both GD and GO males had a significantly higher mortality than those in females. For GO, but not for GD, mortality risk was the highest in the youngest and decreased with increasing age.
  
  
  CONCLUSIONS
  GD and GO were associated with increased mortality, especially in males. In GO, but not in GD patients, there was an inverse relationship between age and mortality. Surprisingly, and in need of further study, mortality was not higher in GO than that in GD individuals.
authors.affiliation: Department of Endocrinology and MetabolismOdense University Hospital, Odense, Denmark.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Schwensen
authors.affiliation: Department of Internal MedicineHospital of Southern Jutland, Sønderborg, Denmark.
authors.forename: Frans
authors.initials: F
authors.lastname: Brandt
authors.affiliation: Department of Endocrinology and MetabolismOdense University Hospital, Odense, Denmark.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
authors.affiliation: Department of Endocrinology and MetabolismOdense University Hospital, Odense, Denmark.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Brix
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006111:Graves Disease / Q000401:mortality; D049970:Graves Ophthalmopathy / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult