title: High age predicts low referral of hyperthyroid patients to specialized hospital departments: evidence for referral bias.
abstract: BACKGROUND
  Hospital-based studies may be hampered by referral bias. We investigated how the phenomenon may influence studies of hyperthyroid patients.
  
  
  METHODS
  By means of a computer-based linkage to the laboratory database and subsequent detailed evaluation of subjects with abnormal test results, we prospectively identified all 1148 patients diagnosed with overt hyperthyroidism in a four-year period in and around Aalborg City, Denmark. Each patient was classified according to nosological type of hyperthyroidism. We studied the referral pattern of patients to local hospital units, and analyzed how referral depended on subtype of disease, sex, age, and degree of biochemical hyperthyroidism.
  
  
  RESULTS
  In a 4-year period, 1032 hyperthyroid patients were diagnosed at primary care offices, and 435 of these (42.2%) were referred to specialized units, 92 patients had hyperthyroidism diagnosed in other hospital departments (referral: 43, 46.7%), and 24 patients had hyperthyroidism diagnosed at the specialized unit after referral for other diseases. Patients suffering from Graves' disease (GD; n=474, median age=65.8 years) were referred more often (odds ratio=1.7 [95% confidence interval 1.3-2.2]) than those diagnosed with multinodular toxic goiter (MNTG; n=525, median age=74.6 years). Higher age was associated with less referral of patients suffering from MNTG (referred vs. nonreferred patients, 64.0 vs. 77.4 years, p<0.001) and GD (43.9 vs. 56.4 years, p<0.001), whereas GD patients referred to a hospital had more severe biochemical hyperthyroidism (serum total triiodothyronine, 4.86 vs. 3.79 nmol/L; serum total thyroxine, 204 vs. 180 nmol/L; both p<0.001). Findings were confirmed in multivariate models reporting age as a significant predictor for referral in both GD and MNTG patients (both p<0.001). Among referred hyperthyroid patients (all combined), those aged up to 40 years (referral rate, 66.8%) were represented 11.6 (6.6-20.6) times more often than those aged 80 years and above (referral rate, 14.8%).
  
  
  CONCLUSIONS
  Hyperthyroid patients referred to a specialized hospital unit were younger (GD+MNTG) and had more severe biochemical hyperthyroidism (GD) compared to nonreferred patients. Thus, referral bias may influence hospital-based studies of hyperthyroid patients, and may hamper external generalization of such studies. Whether the referral bias of hyperthyroid patients in Denmark can be generalized to other countries or cultures remains unknown.
authors.affiliation: 1 Department of Endocrinology and Medicine, Aalborg University Hospital , Aalborg, Denmark .
authors.forename: Allan
authors.initials: A
authors.lastname: Carlé
authors.forename: Inge Bülow
authors.initials: IB
authors.lastname: Pedersen
authors.forename: Hans
authors.initials: H
authors.lastname: Perrild
authors.forename: Lars
authors.initials: L
authors.lastname: Ovesen
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Peter
authors.initials: P
authors.lastname: Laurberg
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003718:Denmark; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012017:Referral and Consultation; D012720:Severity of Illness Index