Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort

Bremner, Alexandra P.; Feddema, Peter; Leedman, Peter J.; Brown, Suzanne J.; Beilby, John P.; Lim, Ee Mun; Wilson, Scott G.; O'Leary, Peter C.; Walsh, John P.

doi:10.1210/jc.2011-3020

Cited by 336Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentHormonal and reproductive studies

Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort

Bremner, Alexandra P., Feddema, Peter, Leedman, Peter J., Brown, Suzanne J., Beilby, John P., Lim, Ee Mun, Wilson, Scott G., O'Leary, Peter C. +1 more·2012·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2011-3020

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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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In the Busselton health survey, TSH levels increased after a 13-year period but with no significant change in FT4.
“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]
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.
“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]

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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: Bremner, Alexandra P.
Leedman, Peter J.
Brown, Suzanne J.
Beilby, John P.
Lim, Ee Mun
Wilson, Scott G.
O'Leary, Peter C.
Walsh, John P.
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
DOI: 10.1210/jc.2011-3020
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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Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort

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