Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study

Abstract

Background: Age- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSHbasal (TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences.

Methods: 2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 - 12 months, and 1 - 5, 6 - 10, 11 - 14, and 15 - 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia(R) Centaur automated immunoassay system.

Results: The final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age.

Conclusion: Our results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.

Figure 1

Reference intervals for TSH of age groups listed in table 2. The central 95% range (2.5^th, 25^th, 50^th, 75^th, and 97.5^th percentiles) is shown. Due to resolution reasons lines start at zero, although no samples were taken within the first hours after birth.

Figure 2

The central 95% range for fT3 in females (2.5^th, 25^th, 50^th, 75^th, and 97.5^th percentiles) is shown.

Figure 3

The central 95% range for fT3 in males (2.5^th, 25^th, 50^th, 75^th, and 97.5^th percentiles) is shown.

Figure 4

Age-related reference values for fT4 (both sexes). The central 95% range (2.5^th, 25^th, 50^th, 75^th, and 97.5^th percentiles) is shown. Due to resolution reasons lines start at zero, although no samples were taken within the first hours after birth.