title: Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease.
abstract: OBJECTIVE
  Thyroid-associated ophthalmopathy (TAO) is a common and debilitating manifestation of Graves disease (GD). Presently little is known about factors that may increase the risk of developing TAO among patients with GD.
  
  
  OBJECTIVE
  To identify risk factors associated with the development of TAO among individuals with newly diagnosed GD.
  
  
  METHODS
  In this longitudinal cohort study, all beneficiaries 18 years of age or older with newly diagnosed GD who were continuously enrolled in a large nationwide US managed care network and who visited an eye care professional 1 or more times from 2001 to 2009 were identified. International Classification of Diseases, Ninth Revision, Clinical Modification billing codes were used to identify those who developed manifestations of TAO. Multivariable Cox regression was used to determine the hazard of developing TAO among persons with newly diagnosed GD, with adjustment for sociodemographic factors, systemic medical conditions, thyrotropin levels, and medical and surgical interventions for management of hyperthyroidism.
  
  
  METHODS
  Manifestations of TAO measured by hazard ratios (HRs) with 95% CIs.
  
  
  RESULTS
  Of 8404 patients with GD who met the inclusion criteria, 740 (8.8%) developed TAO (mean follow-up, 374 days since initial GD diagnosis). After adjustment for potential confounders, surgical thyroidectomy, alone or in combination with medical therapy, was associated with a 74% decreased hazard for TAO (adjusted HR, 0.26 [95% CI, 0.12-0.51]) compared with radioactive iodine therapy alone. Statin use (for ≥60 days in the past year vs <60 days or nonuse) was associated with a 40% decreased hazard (adjusted HR, 0.60 [CI, 0.37-0.93]). No significant association was found for the use of nonstatin cholesterol-lowering medications or cyclooxygenase 2 inhibitors and the development of TAO.
  
  
  CONCLUSIONS
  If prospective studies can confirm our finding that a thyroidectomy and statin use are associated with substantially reduced hazards for TAO among patients with GD, preventive measures for this burdensome manifestation of GD may become a reality.
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Stein
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor.
authors.forename: David
authors.initials: D
authors.lastname: Childers
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor.
authors.forename: Shivani
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Talwar
authors.affiliation: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor.
authors.forename: Bin
authors.initials: B
authors.lastname: Nan
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor3Department of Internal Medicine, School of Medicine, University of Michigan, Ann Arbor.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, University of Michigan, Ann Arbor4Veterans Administration Medical Center, Ann Arbor, Michigan.
authors.forename: Raymond
authors.initials: R
authors.lastname: Douglas
mesh_terms: D000328:Adult; D000368:Aged; D013956:Antithyroid Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000453:epidemiology / Q000628:therapy; D049970:Graves Ophthalmopathy / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006980:Hyperthyroidism / Q000453:epidemiology* / Q000628:therapy; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008329:Managed Care Programs / Q000706:statistics & numerical data; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D014481:United States
chemical_list: D013956:Antithyroid Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007457:Iodine Radioisotopes; D013972:Thyrotropin