Journal article
Natural history of thyroid function in ageing: an individual participant data analysis of 137 488 participants from 31 prospective cohort studies
The lancet. Diabetes & endocrinology, v 14(6), pp 485-497
01 Jun 2026
PMID: 42061390
Abstract
Evidence regarding thyroid function changes with ageing remains inconsistent and the implications of potential changes are unclear. We aimed to investigate ageing-related thyroid function changes and their associations with mortality.
In this individual participant data (IPD) analysis, prospective population-based cohorts were eligible for inclusion when data on thyroid function measurements and mortality were available in individuals aged 18 years and older. Eligible datasets were identified through a systematic search of PubMed. We excluded cohorts of participants with only thyroid disease or thyroid-altering medications, or pregnant individuals. We requested data from all eligible cohorts that agreed to participate in the study. Linear mixed models were used to investigate associations between age and thyroid function, stratified for sex and regional iodine status. Annual changes in thyroid-stimulating hormone (TSH) and free thyroxine (FT) were estimated per individual and categorised into quintiles, with the highest and lowest quintiles defined as increasing and decreasing, respectively, and the rest as stable. Patterns of thyroid function change were identified based on combined TSH and FTevolution. We used cohort-stratified Cox models to assess associations between changing patterns and all-cause mortality. This study is registered with PROSPERO, CRD42023408086.
In this IPD analysis, we analysed data collected between Jan 1, 2011, and Oct 13, 2022, from 31 cohorts across Europe (n=19), the USA (n=5), Asia (n=3), Brazil (n=2), and Australia (n=2; 137 488 participants; 68 322 [49·7%] were female and 69 166 [50·3%] were male; median age 60 years [range 18-106]). Cross-sectionally, older age was associated with higher TSH in iodine-sufficient regions and with lower TSH in iodine-insufficient regions. Longitudinal analyses showed that TSH increased with increasing age regardless of iodine status. The overall increase in TSH from age 18 years to 100 years was 0·61 mIU/L (0·52 SD) for female participants and 0·99 mIU/L (0·76) for male participants from iodine-sufficient regions. Greater variability in population distribution and longitudinal TSH changes was observed in adults aged 65 years or older. Higher FT with older age was suggested cross-sectionally, but longitudinally FT increased in iodine-sufficient regions and decreased in iodine-insufficient regions. Compared with stable thyroid function, all changing patterns were associated with increased all-cause mortality: hazard ratios of 1·80 (95% CI 1·57-2·06) for increasing TSH with stable or decreasing FT; 2·45 (2·01-2·97) for increasing TSH and increasing FT; 2·45 (1·99-3·01) for decreasing TSH with decreasing FT; and 1·94 (1·68-2·24) for decreasing TSH with stable or increasing FT.
Ageing-related changes in thyroid function varied by sex and iodine status. Most individuals had stable thyroid function during ageing with a slight increase in TSH, although older adults displayed greater variability. Patterns of changing thyroid function were associated with an increased all-cause mortality risk, warranting further exploration of the underlying mechanisms and clinical management.
None.
Metrics
1 Record Views
Details
- Title
- Natural history of thyroid function in ageing: an individual participant data analysis of 137 488 participants from 31 prospective cohort studies
- Creators
- Thyroid Studies Collaboration (Collaboration)Yanning Xu - Erasmus MCOla Hysaj - University of BernXiaoyi Qi - Erasmus MCMartin Feller - University of BernAlessandro Pingitore - Istituto di Fisiologia ClinicaSuzanne J Brown - Sir Charles Gairdner HospitalTill Ittermann - Universitätsmedizin GreifswaldMassimo Iacoviello - Polyclinic Medical CenterStella Trompet - Leiden University Medical CenterJi Won Han - Seoul National University Bundang HospitalBörge Schmidt - University of Duisburg-EssenJosé A Sgarbi - Faculdade de Medicina de MaríliaSergio Valdés - Instituto de Investigación Biomédica de MálagaAxel Muendlein - Vorarlberg Institute for Vascular Investigation and TreatmentJohannes Riis - Aalborg University HospitalStig Andersen - Aalborg UniversityHeinz Drexel - Vorarlberg Institute for Vascular Investigation and TreatmentAlexander Teumer - Universitätsmedizin GreifswaldMarcus Dörr - Universitätsmedizin GreifswaldMark P J Vanderpump - OneWelbeck Endocrinology, London, UKNick Wareham - University of CambridgeBert Vaes - KU LeuvenW Edward Visser - Erasmus MCJ Wouter Jukema - Leiden University Medical CenterMisa Imaizumi - Radiation Effects Research FoundationRobin P F Dullaart - University Medical Center GroningenMarco Medici - Erasmus MCHoward A Fink - Geriatric Research Education and Clinical CenterGraziano Ceresini - University of ParmaLuigi Ferrucci - National Institutes of HealthM Arfan Ikram - Erasmus MCGraeme J HankeyGiorgio Iervasi - National Research CouncilRichard Eastell - University of SheffieldDouglas C Bauer - University of California, San FranciscoGraham R Williams - Imperial College LondonKristien Boelaert - University of BirminghamBruce M Psaty - Kaiser Permanente Washington Health Research InstituteDagmar Führer-Sakel - University of Duisburg-EssenStephan J L Bakker - University Medical Center GroningenLambertus A L M Kiemeney - Radboud University Medical CenterNiels P Riksen - Radboud University NijmegenKi Woong Kim - Seoul National University Bundang HospitalFereidoun Azizi - Research Institute for Endocrine SciencesHenry Völzke - Universitätsmedizin GreifswaldBu B Yeap - The University of Western AustraliaSalman Razvi - Newcastle UniversityJacobijn Gussekloo - Leiden University Medical CenterJohn P Walsh - The University of Western AustraliaIsabela M Bensenor - Department of Internal Medicine, University of São Paulo Medical School, São Paulo, BrazilJennifer Mammen - Johns Hopkins UniversityNicolas Rodondi - University of BernAnne R Cappola - University of PennsylvaniaRobin P Peeters - Erasmus MCLayal Chaker - Erasmus MC
- Publication Details
- The lancet. Diabetes & endocrinology, v 14(6), pp 485-497
- Publisher
- ELSEVIER SCIENCE INC
- Number of pages
- 13
- Grant note
- Swiss National Science Foundation: SNSF 320033-200606, 320030-231242
The Thyroid Studies Collaboration is supported by grants from the Swiss National Science Foundation (SNSF 320033-200606 and 320030-231242, awarded to NR) . Additional acknowledgments and cohort-specific grants are described in the appendix (pp 35-36) .
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:001770731500001
- Scopus ID
- 2-s2.0-105038809657
- Other Identifier
- 991022182270904721