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

Abstract

<jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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.</jats:p><jats:p>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 hypothyroidism, 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.</jats:p><jats:p>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.</jats:p>

2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

“…Dynamic changes in thyroid function occur following delivery in the newborn infant, but a serum TSH concentration >5 mU/l can be considered to be abnormal after 1 month of age when modern third-generation assays are used [111,112]. Thereafter, both the serum TSH and thyroid hormone levels continue to decline gradually to values more typical of the adult.…”

Paediatric reference interval and biological variation trends of thyrotropin (TSH) and free thyroxine (T4) in an Asian population

“…By contrast, the lower reference values for TSH were more consistent across the studies. Interestingly, Chaler et al ,8 Kratzsch et al ,10 Marwaha et al ,11 Iwaku et al 13 and their colleagues reported a rise in the lower reference values in children aged between 1 and 12 years that is not seen in the other studies.…”

“…Chaler et al 8 reported considerably higher upper reference values for FT4 in children aged >2 years using indirect sampling approach of outpatients measured by Abbott AxSYM analyser. By contrast, the upper reference values of FT4 that were derived from direct sampling approach were lower when measured by Abbott Architect analyzers 12 14 17 18.…”

“…Since that report, there have been many recent publications on the use of indirect sampling (data-mining) methods to obtain reference intervals for various populations. Indeed, three of 11 (27%) of the reference interval studies, including this study, summarised in online supplementary table S7 employed various forms of statistical analysis to obtain representative data 8 9. Thoughtful application of statistical techniques can transform existing laboratory data into one that reflects a representative population.…”

“…Serum thyroxine binding globulin (TBG) concentration increases with age up to 5 years contributing to the gradual dissociation between total T4 and FT4 8. Subsequently, TBG concentration declines through 15–16 years of age, resulting in a gradual fall in serum total T3 and total T4 concentrations 26.…”