Age-specific thyroid hormone and thyrotropin reference intervals for a pediatric and adolescent population

Background: Establishment of reliable reference intervals remains valuable for confirming validity and advancing standardization across methods and populations. Moreover, knowledge of the measurement uncertainty (U) and of the reference change value (RCV) has important applications in clinical chemistry. Methods: Starting from the information available in the laboratory data base (29,901 subjects) an initial selection was carried out by eliminating all subjects with a clinical or laboratory pathological report; data from 7581 0- to 20-year-old subjects (53.87% girls) remained in the study. These subjects, divided into nine age groups, were used to define reference distribution percentiles (2.5th, 50th and 97.5th) of serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), and free T4 (fT4), as well as U and RCV of these assays. Results: In early infancy, T4 and fT4 values were higher than in the older age groups. Serum T4 95th percentile reference value, useful for the diagnosis of hyperthyroidism, was 142.9 in 20-year-old boys and 230.4 nmol/L in early infants and serum T3 95th percentile was 2.6 and 3.5 nmol/L, respectively, while fT4 2.5th percentile reference value, useful for the diagnosis of hypo-thyroidism, was 9.6 and 13.0 pmol/L, respectively. Serum TSH 97.5th percentile showed less age variation, 4.38-4.88 mIU/L. Performance of the four assays resulted in approximately 20% Us, reflecting simple and complex imprecision, trueness, analytical and functional sensitivity. RCV of serum TSH (58.6%) was larger than for thyroid hormones (28.3%-34.7%), probably due to the high biological variation of this hormone. Conclusions: We have established reference interval for TSH and thyroid hormones, as well as Us for assessing reliability of measurements, and RCVs to alert users on the presence of clinical significant changes.