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Establishing continuous reference intervals for thyroid function tests.

Funda İpekten1,2, Gökmen Zararsız3,4, Halef Okan Doğan5

  • 1Department of Biostatistics, Institute of Health Sciences, Erciyes University, Kayseri, Türkiye.

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|May 5, 2026
PubMed
Summary

This study established age- and gender-specific reference intervals for thyroid function tests, finding significant gender differences in free triiodothyronine (fT3) after age 12. The LMSP model best fit the data, offering a flexible framework for thyroid function evaluation.

Keywords:
GAMLSSThyroid function testsbiochemical markerscontinuous reference intervalspediatric and adult populationthyroid hormones

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Area of Science:

  • Endocrinology
  • Clinical Chemistry
  • Biostatistics

Background:

  • Establishing accurate reference intervals for thyroid function tests is crucial for diagnosing thyroid disorders.
  • Existing reference intervals may not adequately account for age- and gender-specific variations.
  • Continuous modeling approaches offer potential advantages over traditional partitioned methods for defining reference intervals.

Purpose of the Study:

  • To establish age- and gender-specific reference intervals for free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in pediatric and adult populations.
  • To determine age- and gender-specific reference intervals for anti-thyroid peroxidase (anti-TPO) antibodies in adults.
  • To compare partitioned and continuous modeling approaches for determining the most appropriate method for clinical interpretation of thyroid function tests.

Main Methods:

  • Retrospective analysis of laboratory data from Sivas Cumhuriyet University Hospital (2017-2022).
  • Partitioned reference intervals determined using the refineR method.
  • Continuous reference intervals modeled using Generalized Additive Models for Location, Scale, and Shape (GAMLSS) with LMS, LMST, and LMSP distributions.
  • Model selection based on Generalized Akaike Information Criterion (GAIC) values.

Main Results:

  • Significant gender differences in fT3 emerged after age 12 in pediatric subjects, with adult males generally having higher fT3 than females.
  • TSH levels showed minimal gender-related variation in both pediatric and adult groups.
  • The LMSP distribution within the GAMLSS framework provided the best fit for thyroid function parameters in both pediatric and adult datasets, capturing age-related changes effectively.

Conclusions:

  • Continuous reference interval modeling, particularly with the LMSP distribution, offers a superior and flexible approach for evaluating thyroid function across different ages and genders.
  • The established age- and gender-specific reference intervals can improve the clinical interpretation of thyroid function tests.
  • Further research may refine these models for broader clinical application.