title: Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb).
abstract: BACKGROUND
  The National Academy of Clinical Biochemistry (NACB) stresses that the reference intervals for thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) should be based on young men who lack certain risk factors and have serum TSH between 0.5 and 2.0 mIU/L. However, some young men without any of the risk factors have autoantibodies, and cannot be identified by the present tools. A model for reference intervals and cut-off values should not be influenced by the prevalence of risk factors.
  
  
  METHODS
  We developed a model of "composite logarithmic Gaussian distributions" and tested it in 1441 well-characterised subjects without clinically overt thyroid disease.
  
  
  RESULTS
  TPOAb and TgAb could be measured in all individuals. The 97.5% upper limits 1) on a traditional non-parametric scale, 2) according to the NACB criteria, and 3) for our model were 284, 24 and 9.8 kIU/L for TPOAb, and 84, 22 and 19 kIU/L for TgAb, respectively. The decision value (defined as the concentration corresponding to 0.1% false positives) was 15 kIU/L for TPOAb and 31 kIU/L for TgAb. Concentrations above our reference intervals affected the corresponding distribution of TSH values. For TRAb the upper reference limits were 1) 0.75 and 2) 0.75 IU/L, while our model was not applicable to TRAb because only 2-3% of the results were above the functional assay sensitivity.
  
  
  CONCLUSIONS
  In contrast to the NACB guidelines, our model for TPOAb and TgAb is more robust, as it is independent of the characteristics of the reference population.
authors.affiliation: Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark. esther.jensen@ouh.fyns-amt.dk
authors.forename: Esther A
authors.initials: EA
authors.lastname: Jensen
authors.forename: Per Hyltoft
authors.initials: PH
authors.lastname: Petersen
authors.forename: Ole
authors.initials: O
authors.lastname: Blaabjerg
authors.forename: Pia Skov
authors.initials: PS
authors.lastname: Hansen
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Brix
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011989:Receptors, Thyrotropin / Q000097:blood / Q000276:immunology*; D012016:Reference Values; D012042:Registries; D013954:Thyroglobulin / Q000097:blood / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D018433:Twin Studies as Topic
chemical_list: D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013954:Thyroglobulin; D007453:Iodide Peroxidase