Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry

OBJECTIVE: Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. METHODS: Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). RESULTS: Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). CONCLUSION: Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population.