title: Indirect estimation of age-related reference limits of thyroid parameters: a cross-sectional study of outpatients' results.
abstract: OBJECTIVE
  Defining adequate reference limits (RLs) for thyroid hormones is an important task for support monitoring and the treatment of subclinical thyroid disease. We determined whether there are age-related RLs for thyroid parameters in male and female outpatients free of overt thyroid disease.
  
  
  METHODS
  We analyzed 22,860 results (11,440 male and 11,420 female outpatients above the age of 18) for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that were stored in our laboratory information system between 2008 and 2011. We calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters.
  
  
  RESULTS
  Our results indicate higher TSH levels with ageing, with a significant difference (p < 0.05) between the 97.5th centiles for males and females older than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9 pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect estimates of the 97.5th centiles for TSH for males and females were not significantly different and were below the generally recommended upper limit (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically significant change in mean T3 values in the analyzed population.
  
  
  CONCLUSIONS
  This cross-sectional study indicates change in TSH and fT4 levels with ageing and gender-related upper limits. This suggests that by using indirect estimation a laboratory could provide clinicians with more accurate gender- and age-specific RLs for thyroid parameters.
authors.affiliation: Center for Medical Biochemistry, Clinical Center of Serbia , Belgrade , Serbia.
authors.forename: Neda
authors.initials: N
authors.lastname: Milinković
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ignjatović
authors.forename: Miloš
authors.initials: M
authors.lastname: Žarković
authors.forename: Snežana
authors.initials: S
authors.lastname: Jovičić
authors.forename: Branimir
authors.initials: B
authors.lastname: Radosavljević
authors.forename: Sandra
authors.initials: S
authors.lastname: Singh
authors.forename: Nada
authors.initials: N
authors.lastname: Majkić-Singh
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012016:Reference Values; D012727:Sex Characteristics; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: Reference limits; TSH; subclinical thyroid disease; thyroid parameters