Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study
Open accessAbstract
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.
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Cross-sectional studies generally show higher TSH upper limits in younger children (<5 years) compared with older children (≥5 years), with a gradual decline in TSH concentration towards adult age (15-18 years), and lower FT3 with higher increases in FT4 concentrations from age 4 years.
“Cross-sectional studies generally show higher TSH upper limits in younger children (<5 years) compared with older children (≥5 years), with a gradual decline in TSH concentration towards adult age (15-18 years), 119-124 and lower FT3 with higher increases in FT4 concentrations from age 4 years.[125][126][127][128]”
From Hypothyroidism (2024) · cites this paper as [121]
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Experimental — accuracy not yet measuredThyroid hormone levels change markedly during childhood and adult reference intervals are not universally applicable to children.
“Importantly, thyroid hormone levels change markedly during childhood and adult reference intervals are not universally applicable to children [22].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [22]
Small studies in children indicate marked variation in thyroid hormone reference ranges such that adult reference intervals are not universally applicable to children.
“Small studies in children indicate marked variation in thyroid hormone reference ranges such that adult reference intervals are not universally applicable to children [33–35].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [33]
Cross-sectional studies generally show higher TSH upper limits in younger children (<5 years) compared to older children, with a gradual decline in TSH concentration as adult age is approached.
“Cross-sectional studies generally show higher TSH upper limits in younger children (< 5 years) compared to older children, with a gradual decline in TSH concentration as the adult age is approached [33, 36–39].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [33]
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References 42 · Cited by 203
- Authors
- Kapelari, K., Kirchlechner, C., Högler, W., Schweitzer, K., Virgolini, I., & Moncayo, R.
- Affiliations
- Innsbruck Medical University (AT)
- Corresponding author
- Kapelari, Klaus
- Venue
- BMC Endocrine Disorders
- Published
- 2008-11-27
- Volume
- 8
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1472-6823 (ISSN-L)
- PMC
- PMC2645400
- OpenAlex
- W2075021290
- Cited by
- 203
- References
- 42
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 14 · 2023: 23 · 2022: 10 · 2021: 17 · 2020: 8 · 2019: 21 · 2018: 15 · 2017: 14 · 2016: 11 · 2015: 13 · 2014: 9 · 2013: 11 · 2012: 10
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Endocrine Disorders (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- pediatric reference intervals, thyroid hormones, thyroid-stimulating hormone, free T3, free thyroxine, age-related reference values, sex differences, neonatal thyroid function
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