Establishing Age- and Sex-Specific Reference Intervals for Thyroid Function Tests in the Older People of Eastern Anatolia: A Population-Based Indirect Approach

TL;DR

This study establishes age- and sex-specific reference intervals for thyroid tests in older adults in Eastern Turkey to improve clinical accuracy.

Contribution

The study provides new, locally relevant reference intervals for thyroid hormones in older populations using an indirect statistical method.

Findings

fT3 levels decrease with age, while TSH and fT4 remain stable across age subgroups.

Males had higher fT3 levels, while females had higher fT4 and TSH levels.

Sex-specific reference intervals are recommended for thyroid function tests in this population.

Abstract

Background and Objectives: Given that hormone levels vary with age, the application of age-specific reference intervals in older populations is clinically essential. In this study, we aimed to establish age- and sex-specific reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy individuals aged ≥65 in Eastern Turkey using an indirect statistical method. Materials and Methods: This retrospective study included 3835 individuals (1986 males and 1849 females) who were evaluated at Elazığ Fethi Sekin City Hospital between 2020 and 2025. According to the Clinical and Laboratory Standards Institute (CLSI) C28-A3 guidelines, reference intervals were determined using a laboratory database–based indirect reference interval estimation approach with nonparametric percentile methods following a posteriori reference population selection, and the Harris–Boyd criteria were applied for age and sex partitioning. Results: The established reference intervals for those aged ≥65 years were 2.40–4.03 pg/mL for fT3, 0.60–1.27 ng/dL for fT4, and 0.41–3.94 mIU/L for TSH. While fT3 levels declined with age, TSH and fT4 levels did not differ consistently across age subgroups. Sex-based differences were significant: fT3 levels were higher in males, whereas fT4 and TSH levels were higher in females. According to the Harris–Boyd analysis, separate reference intervals are recommended for males and females. Conclusions: For healthy older individuals living in Eastern Türkiye, sex-specific reference intervals should be used for thyroid function tests, whereas age-specific reference intervals are sufficient for fT3.

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