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Paediatric reference interval and biological variation trends of thyrotropin (TSH) and free thyroxine (T4) in an
Tze Ping Loh1, Sunil Kumar Sethi1, Michael Patrick Metz2
1Department of Laboratory Medicine, National University Hospital, Singapore, Singapore.
Insights
This study establishes reference intervals and biological variation for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in Asian children. Data shows age-related changes, highlighting challenges in standardizing pediatric thyroid reference values globally.
Area of Science:
- Pediatric Endocrinology
- Clinical Biochemistry
- Thyroid Function Testing
Background:
- Thyroid function tests, including TSH and FT4, are crucial for diagnosing pediatric thyroid disorders.
- Establishing accurate reference intervals and understanding biological variation are essential for reliable interpretation of these tests in diverse populations.
- Existing pediatric thyroid reference intervals show significant heterogeneity, complicating clinical practice.
Purpose of the Study:
- To define age-specific reference intervals for TSH and FT4 in a mixed Asian pediatric population.
- To characterize the biological variation of TSH and FT4 in this cohort.
- To compare findings with existing international reports on pediatric thyroid function.
Main Methods:
- Retrospective analysis of TSH and FT4 measurements from children over a 7-year period (2008-2014).
- Application of the Lambda-Mu-Sigma (LMS) method for deriving age-related reference intervals.
- Calculation of age-partitioned biological variation data following established recommendations.
Main Results:
- TSH and FT4 levels were highest at birth and decreased with age in the study population.
- Both within-individual and between-individual biological variation for TSH and FT4 were greater at birth, declining with age.
- The derived data generally aligned with previous studies, though direct numerical comparison was limited by heterogeneity in methodologies and populations.
Conclusions:
- This study provides essential centile trends and reference values for TSH and FT4 in a mixed Asian pediatric cohort.
- It offers valuable age-partitioned biological variation data, filling critical knowledge gaps in pediatric thyroid function.
- The observed variability in published reference intervals underscores the challenges in harmonizing pediatric thyroid reference ranges and establishing universal clinical cut-offs.
Aims:
To describe the reference intervals and biological variation data for thyrotropin (TSH) and free thyroxine (FT4) in a mixed Asian population using an indirect sampling approach and to compare them with published reports.
Methods:
TSH and FT4 of children measured once or twice over a 7-year period (2008-2014) at primary-care and tertiary-care settings were extracted from the laboratory information system. After excluding outliers, age-related reference intervals were derived using the Lambda-Mu-Sigma (LMS) approach, while age-partitioned biological variation data were obtained according to recommendations by Fraser and Harris.
Results:
Both TSH and FT4 were very high at birth and declined with age. Similarly within-individual and between-individual biological variations were higher for both TSH and FT4 at birth and also declined with age. Our data were broadly similar to previous studies. Significant heterogeneity in study population and methods prohibited direct numerical comparison between this and previously published studies.
Conclusions:
This study fills two important gaps in our knowledge of paediatric thyroid function by reporting the centile trends (and reference values) in a mixed Asian population, as well as providing age-partitioned biological variation data. The variation in published reference intervals highlights the difficulty in harmonising paediatric thyroid reference intervals or recommending universal clinical cut-offs.
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