Evidence map›Paper›PMID 42163258›Full record

ArticleBMC medicine2026

Application of age- and sex-specific reference intervals for thyroid-stimulating hormone and free thyroxine in evaluating incidence and trends of thyroid dysfunctions: A population-based cohort study.

Jiawen Lu, Ching-Man Tang, Grace Meng-Qin Ge, Kenneth King-Yip Cheng, Keith Cheuk-Lun Lee, Kathryn Choon-Beng Tan, Stanley Kam-Ki Lam, Elaine Yun-Ning Cheung, Ching-Lung Cheung, Gloria Hoi-Yee Li

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Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Jiawen LuDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.
Ching-Man TangDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.
Grace Meng-Qin GeDepartment of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Kenneth King-Yip ChengDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.
Keith Cheuk-Lun LeeDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.
Kathryn Choon-Beng TanDepartment of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Stanley Kam-Ki LamThe Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Elaine Yun-Ning CheungHong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Ching-Lung CheungDepartment of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Gloria Hoi-Yee LiDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China. gloria-hy.li@polyu.edu.hk.

Funding

Health Bureau 20211121
6 · The paper itself

Abstract

backgroundDiagnosis of thyroid dysfunctions heavily relies on the biochemical tests for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Conventional laboratory-specific reference intervals (RIs) for TSH and FT4 are uniform across adults and ignore age-, sex-, and time-related variations, which may lead to misdiagnosis of thyroid dysfunction. This study aimed to establish the age- and sex-specific RIs for TSH and FT4, and to evaluate their implications on the incidence and secular trends of thyroid dysfunctions.

methodsUsing a population-based electronic health record database in Hong Kong, we identified individuals without thyroid-related disorders who had valid TSH (N = 2,111,661) and FT4 (N = 825,522) measurements from 2006 to 2019. After harmonizing data across multiple institutions, we derived age- and sex-specific lower and upper reference limits (LRLs and URLs) for TSH and FT4 using the 2.5th and 97.5th percentiles of the biomarker distribution in seven age groups for both females and males. In comparison with the laboratory-specific RIs, we reclassified the thyroid status of the cohort individuals. We also compared the standardized incidence rates and secular trends in thyroid dysfunctions defined by the age- and sex-specific RIs and the conventional RIs.

resultsTSH and FT4 distributions varied by age, sex, and calendar year. Age- and sex-specific RIs for TSH and FT4 were significantly wider among elderly individuals (≥ 70 years) compared to the youngest adults (18-29 years). Among those with both TSH and FT4 measurements, 30.78% were classified as having thyroid dysfunctions using laboratory-specific RIs, whereas applying age- and sex-specific RIs reduced this proportion to 18.57%. The use of age- and sex-specific RIs was associated with lower observed incidence rates and revealed estimates of incidence and secular trends that are likely closer to the underlying disease burden.

conclusionsAge- and sex-specific RIs could mitigate misdiagnosis of thyroid dysfunctions, thereby improving diagnostic accuracy and enabling more precise monitoring of secular trends. The secular trends and joinpoints identified for the age- and sex-specific URLs and LRLs of TSH and FT4 from 2006 to 2019 indicate that regular RI review is needed to ensure their continued clinical relevance. Future validation in geographically and ethnically diverse populations is warranted.

Indexed as

Thyroid DiseasesThyrotropinThyroxineAdolescentAdultAgedAged, 80 and overAge FactorsChildCohort StudiesFemaleHong KongHumansIncidenceMaleMiddle AgedThyrotropinThyroxineAge- and sex-specific reference intervalsElectronic health recordsFree thyroxineThyroid-stimulating hormone

Identifiers

PMID42163258
PMCPMC13360042

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.