Are traditional reference ranges adequate for geriatric individuals? an indirect approach to thyroid testing

Abstract Objectives Physiological changes during aging may complicate the interpretation of thyroid function tests in elderly individuals. This study aimed to establish age- and sex-specific indirect reference intervals for thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) in individuals aged 65 years and older. Methods Large-scale laboratory data collected between 2016 and 2025 were analyzed. Reference intervals were calculated using the refineR package with a Box-Cox transformation model and bootstrap resampling. Subgroup analyses were performed by age (65–74, 75–84, 85–96) and sex. Results The upper limit of TSH decreased with advancing age, particularly in female, while FT3 levels showed a significant decline in older age groups. FT4 intervals remained relatively stable across age groups, though female exhibited higher upper limits compared to male. Conclusions Manufacturer-provided adult reference intervals may be inadequate or less representative for the geriatric population. Implementing age- and sex-specific reference intervals in clinical practice will improve diagnostic accuracy and help prevent misdiagnosis and unnecessary treatment.