Free T4 Age-Specific Reference Intervals from Birth to the 10 ^th Decade of Life Using Direct Dialysis

<b><i>Background:</i></b> Free thyroxine (FT4) reference intervals (RIs) provided by many laboratories do not adequately represent the differences in FT4 levels observed across age groups, limiting their usefulness in the diagnosis and management of disease, most particularly at the extremes of age. Interpretive criteria specific to neonates, young children, and older adults are rarely provided. This work was undertaken to develop comprehensive age-based RIs from birth to age 100 to provide clinicians with precise context for result interpretation. <b><i>Methods:</i></b> RIs were calculated through multi-modal decomposition (MMD) analysis performed on de-identified retrospective FT4 results from specimens submitted for routine testing by direct dialysis at a commercial reference laboratory. Intervals were validated using a separate data set. The study population for MMD analysis included individuals from age 0 days to 100 years who submitted specimens for FT4 testing. <b><i>Results:</i></b> A total of 1,862,273 results were included in the analysis. MMD analysis yielded 14 distinct RIs by age. FT4 intervals were broadest, with higher upper reference limit (URL) and lower reference limit (LRL) at birth, narrowing toward adult ranges throughout childhood. A mild increase in the URL was observed in older adults. <b><i>Conclusions:</i></b> The development and validation of FT4 RIs provides interpretive criteria for FT4 results for patients throughout the lifespan. By providing RIs for distinct neonatal, pediatric, and adult age groups, this work enables clinicians to evaluate FT4 results in the appropriate context, allowing more accurate classification of abnormal results.