Outcomes of Thyroid Dysfunction in People Aged Eighty Years and Older: An Individual Patient Data Meta-Analysis of Four Prospective Studies (Towards Understanding Longitudinal International Older People Studies Consortium)
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Background: Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations in very old persons, however, are currently lacking. This study aimed to investigate the associations between (sub-)clinical thyroid dysfunction and disability in daily living, cognitive function, depressive symptoms, physical function, and mortality in people aged 80 years and older. Methods: Four prospective cohorts participating in the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included. We performed a two-step individual participant data meta-analysis on source data from community-dwelling participants aged 80 years and older from the Netherlands, New Zealand, United Kingdom, and Japan. Outcome measures included disability in daily living (disability in activities of daily living [ADL] questionnaires), cognitive function (Mini-Mental State Examination [MMSE]), depressive symptoms (Geriatric Depression Scale [GDS]), physical function (grip strength) at baseline and after 5 years of follow-up, and all-cause five-year mortality. Results: Of the total 2116 participants at baseline (mean age 87 years, range 80–109 years), 105 participants (5.0%) were overtly hypothyroid, 136 (6.4%) subclinically hypothyroid, 1811 (85.6%) euthyroid, 60 (2.8%) subclinically hyperthyroid, and 4 (0.2%) overtly hyperthyroid. Participants with thyroid dysfunction at baseline had nonsignificantly different ADL scores compared with euthyroid participants at baseline and had similar MMSE scores, GDS scores, and grip strength. There was no difference in the change of any of these functional measures in participants with thyroid dysfunction during five years of follow-up. Compared with the euthyroid participants, no 5-year survival differences were identified in participants with overt hypothyroidism (hazard ratio [HR] 1.0, 95% confidence interval [CI 0.6–1.6]), subclinical hypothyroidism (HR 0.9 [CI 0.7–1.2]), subclinical hyperthyroidism (HR 1.1 [CI 0.8–1.7]), and overt hyperthyroidism (HR 1.5 [CI 0.4–5.9]). Results did not differ after excluding participants using thyroid-influencing medication. Conclusions: In community-dwelling people aged 80 years and older, (sub-)clinical thyroid dysfunction was not associated with functional outcomes or mortality and may therefore be of limited clinical significance.
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No association between overall mortality and subclinical hypothyroidism was confirmed by a recent meta-analysis of four prospective cohort studies including subjects older than 80 years.
“Similarly, no association between overall mortality and SC-HT was confirmed by an extremely recent meta-analysis performed on four prospective cohort studies including subjects older than 80 years, which showed no correlation between SC-HT and all-cause mortality[28].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [28]
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Abouglila, K., Mukhtar, S. F., Hajjaji, I. M., Sheikh, S., & Beshyah, S. (2024) · Journal of Diabetes and Endocrine Practice · doi:10.1055/s-0044-1788596
Hormones and Antiaging Medicine: Thyroid Hormones and Antiaging
Hamaguchi, M. (2024) · Springer eBooks · doi:10.1007/978-981-97-8514-8_45
Zhao, L., Mu, R., Zhang, X., Wang, S., Zhao, M., & Shang, H. (2025) · Research Square · doi:10.21203/rs.3.rs-6780346/v1
Kurzweil, E., Nissan, R., Sharir-Levy, D., Elazar, A., Kornyukov, N., & Hershkovitz, A. (2026) · Archives of Gerontology and Geriatrics Plus · doi:10.1016/j.aggp.2026.100267
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“63 – 0.94) (50),andpatients aged 70 – 79 with TSH values between 4.5 and 7 mIU/L showed improved mobility (51).”
Influential
- Authors
- Du Puy, R. S., Poortvliet, R. K. E., Mooijaart, S. P., den Elzen, W. P. J., Jagger, C., Pearce, S. H. S., Arai, Y., Hirose, N., Teh, R., Menzies, O., Rolleston, A., Kerse, N., Gussekloo, J., & for the TULIPS Consortium
- Affiliations
- Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
- Leiden University Medical Center (NL)
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
- Newcastle Hospitals - Campus for Ageing and Vitality (GB)
- Royal Victoria Infirmary (GB)
- Keio University (JP)
- University of Auckland (NZ)
- ORCID
- Venue
- Thyroid®
- Publisher
- SAGE Publications
- Published
- 2021-04
- Volume
- 31
- Issue
- 4
- Pages
- 552-562
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W3091283751
- Semantic Scholar
- 79bb7d81c935ffef554c6b61bdfd637d6a7209fb
- Cited by
- 27
- References
- 62
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Medical Research Council (MR/J50001X/1)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- thyroid dysfunction, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, overt hyperthyroidism, oldest old, activities of daily living, cognitive function, depressive symptoms, physical function, grip strength, mortality, community-dwelling older adults, individual patient data meta-analysis, functional decline, thyroid hormone replacement
- MeSH terms
- Functional Status, Age Factors, Aged, 80 and over, Humans, Hyperthyroidism, Hypothyroidism, Mental Health, Prognosis, Prospective Studies, Risk Factors, Thyroid Function Tests, Time Factors, Geriatric Assessment, Risk Assessment, Asymptomatic Diseases
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