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Paediatric reference interval and biological variation trends of thyrotropin (TSH) and free thyroxine (T4) in an Asian population
  1. Tze Ping Loh1,
  2. Sunil Kumar Sethi1,
  3. Michael Patrick Metz2,3
  1. 1Department of Laboratory Medicine, National University Hospital, Singapore, Singapore
  2. 2Division of Chemical Pathology, SA Pathology, Women's and Children's Hospital, Adelaide, South Australia, Australia
  3. 3School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia
  1. Correspondence to Dr Tze Ping Loh, Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore; tploh{at}


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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