Establishing continuous reference intervals for thyroid function tests.

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.