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A bivariate reference interval for TSH and free thyroxine.

Arne Åsberg1, Gustav Mikkelsen1,2

  • 1Department of Clinical Chemistry, St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.

Scandinavian Journal of Clinical and Laboratory Investigation
|December 9, 2024
PubMed
Summary
This summary is machine-generated.

A new bivariate reference interval for thyroid hormones, including thyroid-stimulating hormone (TSH) and free thyroxine (FT4), offers a more accurate assessment of thyroid function compared to traditional univariate methods. This approach improves classification accuracy in clinical settings.

Keywords:
Bivariate reference intervalMahalanobis distanceTSHconfidence ellipsefree thyroxine

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Area of Science:

  • Endocrinology
  • Clinical Chemistry
  • Biostatistics

Background:

  • Thyroid status is commonly assessed using serum TSH and FT4 levels.
  • Current practice relies on univariate reference intervals for individual hormone measurements.
  • Bivariate analysis may offer a more comprehensive evaluation of thyroid function.

Purpose of the Study:

  • To construct and evaluate a bivariate reference interval for serum TSH and FT4.
  • To compare the diagnostic performance of bivariate versus univariate reference intervals for thyroid function.

Main Methods:

  • A bivariate reference interval was constructed using Mahalanobis distances from data of 495 healthy donors.
  • Box-Cox transformation was applied to hormone measurements.
  • Classification agreement was assessed using kappa statistics in a large outpatient cohort (177,514 specimens).

Main Results:

  • The bivariate reference interval classified 76.6% of specimens as normal, compared to 68.9% (95% univariate) and 76.2% (97.5% univariate).
  • Higher agreement was observed between the bivariate and the 97.5% univariate intervals (kappa=0.881) than the 95% univariate interval (kappa=0.790).
  • The bivariate method demonstrated improved classification of thyroid function.

Conclusions:

  • Bivariate reference intervals provide a more accurate assessment of thyroid function than univariate intervals.
  • This method enhances the interpretation of TSH and FT4 measurements in clinical practice.
  • Further validation is needed to confirm the clinical superiority of the bivariate approach.