The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort
Abstract
CONTEXT: In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or occult thyroid failure. METHODS: We measured serum TSH, free T(4), thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469. RESULTS: At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter [95% confidence interval (CI) 0.27, 0.38, P < 0.001], whereas mean free T(4) concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each decade of baseline age. People with higher baseline TSH values had proportionally smaller increases in TSH, with each additional 1.0 mU/liter of baseline TSH associated with a 0.13 mU/liter decrease (age and gender adjusted) in ΔTSH (95% CI 0.09, 0.16). The ΔTSH did not differ significantly by CAPZB genotype. CONCLUSIONS: Aging is associated with increased serum TSH concentrations, with no change in free T(4) concentrations. The largest TSH increase is in people with the lowest TSH at baseline. This suggests that the TSH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.
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“The first, a study of 908 individuals in the Busselton health survey, showed that TSH levels increased after a 13-year period but with no significant change in FT4 [97].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [97]
In the citing paper
“Furthermore, a multitude of physiological and pathophysiological influences modulates the relationship between TSH and thyroid hormones at various sites of action, thereby influencing the location of the set point in health and disease (Table 2) (8, 9, 76, 91–111).”
From Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment (2015) · cites this paper as [95]
Citations
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Bricaire, L. (2019) · Elsevier eBooks · doi:10.1016/b978-2-294-74372-6.00033-3
Parker, D., & Heflin, M. T. (2020) · Springer eBooks · doi:10.1007/978-3-319-47771-8_3
McKee, A. M., & Morley, J. E. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780198701590.003.0148
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“…varied among the studies, with some studies including exclusively elderly individuals or a high proportion of elderly (Gopinath et In addition, the metabolism of thyroid hormones declines with increased age, resulting in an increase in the TSH level (Bremner et al., 2012; Waring et al., 2012).”
Mo, C., Wang, Y., Tong, T., Chen, H., Guo, Y., & Zhong, L. (2023) · Research Square · doi:10.21203/rs.3.rs-2592836/v1
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TSH Spontaneously Normalizes in Many Older Adults with Subclinical Hypothyroidism
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Role of Artificial Intelligence in Thyroid Disorder
Guleria, D., & Garg, V. K. (2023) · International Conference on Innovative Sustainable Computational Technologies (CISCT) · doi:10.1109/cisct57197.2023.10351217
The effect of periodontal status on the TSH and FT4 levels
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“20,21 Of note, Lee et al. found no significant difference among individuals aged below 60 years with regard to serum TSH values.”
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Abdullah, N. A. A.-H., & Hassan, E. A. (2025) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-025-03937-0
“The Busselton survey, a recent longitudinal study from Western Australia, showed for the first time that blood TSH levels increase with age without a noticeable shift in free T4 concentrations [23].”
Special Considerations in the Treatment of Hypothyroidism
Hoermann, R., & Dietrich, J. W. (2025) · Springer eBooks · doi:10.1007/978-981-96-3682-2_12
Zhao, L., Mu, R., Zhang, X., Wang, S., Zhao, M., & Shang, H. (2025) · Research Square · doi:10.21203/rs.3.rs-6780346/v1
Hypothyreose - Hausärztliche Diagnostik und Therapie
Schübel, J. (2025) · CME · doi:10.1007/s11298-025-4258-8
Changes in serum TSH across the adult lifespan: 22-year follow-up of the HUNT Study
Åsvold, B. O., Denos, M., Taylor, P. N., Razvi, S., Bjøro, T., Brumpton, B. M., & Haug, E. B. (2026) · European Journal of Endocrinology · doi:10.1093/ejendo/lvag097
Additional file 1 of Hypothyroidism after hemithyroidectomy: a systematic review and meta-analysis
Cooper, D., Kaur, R., Ayeni, F. E., Eslick, G. D., & Edirimanne, S. (2024) · Figshare · doi:10.6084/m9.figshare.26740619
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Additional file 2 of Hypothyroidism after hemithyroidectomy: a systematic review and meta-analysis
Cooper, D., Kaur, R., Ayeni, F. E., Eslick, G. D., & Edirimanne, S. (2024) · Figshare · doi:10.6084/m9.figshare.26740622
Role of thyroid dysfunction in long-term psychological prognosis of sepsis
Zhao, E., Hu, C., Jia, W., Zhang, T., & Shao, H. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1699248
“Given that age is signi fi cantly associated with both sepsis prognosis and thyroid function (26, 27), patients were divided into a middle-aged ( 60 years old) and an elderly ( ≥ 60 years old) group, and the prior analysis was replicated (Table 4).”
Kikhtyak, O. P., Moskva, K. A., Сергієнко, В. О., & Kikhtiak, T. A. (2025) · Lviv clinical bulletin · doi:10.25040/lkv2025.04.038
Thyroid disorders in the elderly
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“39 Our fi ndings also con fi rmed that sex is one of the objective factors in fl uencing TSH levels.”
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“It has also been proposed that aging may be associated with reduced TSH bioactivity or altered thyroidal responsiveness to TSH, although the underlying mechanisms remain incompletely understood [10].”
Thyroid hormones and energy metabolism in amyotrophic lateral sclerosis
Novikova, L., Lang, C., Tumani, H., Klose, V., Kassubek, J., Dreyhaupt, J., Dupuis, L., Wabitsch, M., & Ludolph, A. (2026) · Brain Communications · doi:10.1093/braincomms/fcag198
“33,34 Our study revealed a significant negative correlation between TSH levels and age in ALS patients, particularly in males ( r = − 0.1210, P 0.05), suggesting a sex-dependent modulation of thyroid function.”
InfluentialJiao, Y., Sun, J., Li, Y., & Mao, F. (2026) · Journal of Cardiothoracic Surgery · doi:10.1186/s13019-026-04589-6
“Age plays a significant role in assessing CVD risk and is also closely related to the HPT axis, which changes with advancing age [4, 29, 30].”
Zhao, L., Mu, R., Zhang, X., Wang, S., Zhao, M., & Shang, H. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1857191
Thyroid ultrasound and thyroid function findings in 3029 hospital employees: a short report
Lu, X., Yang, W., & Zhang, F. (2026) · International Journal of Radiation Research · doi:10.66224/ijrr.24.3.43
Dadel, E. V., Oraon, A. P. O., & Aziz, T. (2026) · PAIN JOINTS SPINE · doi:10.1922/pjs.16.7s.2026.1212
“Longitudinal observations from community cohorts have similarly suggested that FT4 may remain relatively stable with advancing age [3].”
Akbaş, S., Uçkun, A., Gümüşçubuk, O., Yalçın, A., Varlı, M., & Atmış, V. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15208059
“Large cross-sectional datasets have frequently shown an upward shift in the TSH distribution with age [4,5], and longitudinal data have also described within-person increases [6].”
Li, H., Wang, N., Ran, X., Fan, Z., Zhao, T., & Ma, X. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.2000192
“A longitudinal cohort by Bremner et al. revealed no evidence accompanying T4 changes, suggesting that changes in serum TSH are not the consequence of pituitary-thyroid axis feedback (21, 22).”
Metadata
- Authors
- Bremner, A. P., Feddema, P., Leedman, P. J., Brown, S. J., Beilby, J. P., Lim, E. M., Wilson, S. G., O'Leary, P. C., & Walsh, J. P.
- Affiliations
- The University of Western Australia (AU)
- Curtin University (AU)
- Corresponding author
- Walsh, John P.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-05
- Volume
- 97
- Issue
- 5
- Pages
- 1554-1562
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1978327859
- Cited by
- 336
- References
- 33
- Citations by year
- 2026: 22 · 2025: 18 · 2024: 22 · 2023: 30 · 2022: 23 · 2021: 30 · 2020: 16 · 2019: 27 · 2018: 27 · 2017: 30 · 2016: 20 · 2015: 23 · 2014: 12 · 2013: 24 · 2012: 9
- FWCI
- 17.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- eSpace (Curtin University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- serum TSH, free thyroxine, healthy aging, thyroid peroxidase antibodies, thyroglobulin antibodies, longitudinal cohort
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Aging, Autoantibodies, Cross-Sectional Studies, Female, Health Surveys, Humans, Iodide Peroxidase, Longitudinal Studies, Male, Middle Aged, Thyroglobulin, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine
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