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

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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.·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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Background
The current debate over treatment of subclinical hypothyroidism to prevent cardiovascular complications
Chrysant, S. G. (2020) · International Journal of Clinical Practice · doi:10.1111/ijcp.13499 · Cited by 48
The landscape of expression and alternative splicing variation across human traits
García-Pérez, R., Ramírez, J. M., Ripoll-Cladellas, A., Chazarra-Gil, R., Oliveros, W., Soldatkina, O., Bosio, M., Rognon, P. J., Capella-Gutiérrez, S., Calvo, M., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100244 · Cited by 44
Hypothyroidism in the Elderly: Who Should Be Treated and How?
Calsolaro, V., Niccolai, F., Pasqualetti, G., Tognini, S., Magno, S., Riccioni, T., Bottari, M., Caraccio, N., & Monzani, F. (2018) · Journal of the Endocrine Society · doi:10.1210/js.2018-00207 · Cited by 52
“Indeed, a large, prospective cohort study on 3233 subjects older than 65 years did not show any relationship between cardiovascular disorders and sHT, apart from an association with the development of atrial fibrillation [43].”
Background
The log TSH–free T4 relationship in a community‐based cohort is nonlinear and is influenced by age, smoking and thyroid peroxidase antibody status
Brown, S. J., Bremner, A. P., Hadlow, N. C., Feddema, P., Leedman, P. J., O'Leary, P. C., & Walsh, J. P. (2016) · Clinical Endocrinology · doi:10.1111/cen.13107 · Cited by 46
Self-citation
Subclinical Hypothyroidism and Indices for Metabolic Syndrome in Japanese Women: One-Year Follow-Up Study
Nakajima, Y., Yamada, M., Akuzawa, M., Ishii, S., Masamura, Y., Satoh, T., Hashimoto, K., Negishi, M., Shimomura, Y., Kobayashi, I., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1353 · Cited by 47
TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects
Jun, J. E., Jin, S., Jee, J. H., Bae, J. C., Hur, K. Y., Lee, M., Kim, S. W., & Kim, J. H. (2017) · Endocrine · doi:10.1007/s12020-016-1221-1 · Cited by 44
Overtime trend of thyroid hormones and thyroid autoimmunity and ovarian reserve: a longitudinal population study with a 12-year follow up
Bahri, S., Tehrani, F. R., Amouzgar, A., Rahmati, M., Tohidi, M., Vasheghani, M., & Azizi, F. (2019) · BMC Endocrine Disorders · doi:10.1186/s12902-019-0370-7 · Cited by 44
Age- and Sex-Specific TSH Upper-Limit Reference Intervals in the General French Population: There Is a Need to Adjust Our Actual Practices
Raverot, V., Bonjour, M., du Payrat, J. A., Perrin, P., Roucher‐Boulez, F., Lasolle, H., Subtil, F., & Borson‐Chazot, F. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9030792 · Cited by 43
“Another limitation of the present study is that patients were not followed over time, but published longitudinal studies have reported that the increase in TSH over time was limited [3].”
Background
Association Between Exposure to Ambient Air Pollution and Thyroid Function in Korean Adults
Kim, H., Kwon, H., Yun, J. M., Cho, B., & Park, J. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa338 · Cited by 43
Familial longevity is associated with higher tsh secretion and strong TSH-fT3 relationship
Jansen, S. W., Roelfsema, F., van der Spoel, E., Akintola, A. A., Postmus, I., Ballieux, B. E., Slagboom, P. E., Cobbaert, C. M., van der Grond, J., Westendorp, R. G., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2624 · Cited by 41
“In population-based studies, mean TSH levels tend to increase with age(35-38), although some studies suggest that 24-h TSH levels are decreased in aging men(39).”
Background
The ageing thyroid: implications for longevity and patient care
van Heemst, D. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00911-7 · Cited by 43
“Several longitudinal studies analysed individual trajectories of thyroid status parameters over time and related these to relevant outcomes after follow-up 48–52 .”
Background
Thyroid hormones in extreme longevity
Garasto, S., Montesanto, A., Corsonello, A., Lattanzio, F., Fusco, S., Passarino, G., Giarritta, V. P., & Corica, F. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.03.002 · Cited by 41
Reference ranges of serum TSH , FT 4 and thyroid autoantibodies in the Thai population: the national health examination survey
Sriphrapradang, C., Pavarangkoon, S., Jongjaroenprasert, W., Chailurkit, L., Ongphiphadhanakul, B., & Aekplakorn, W. (2013) · Clinical Endocrinology · doi:10.1111/cen.12371 · Cited by 41
The aging thyroid
Tabatabaie, V., & Surks, M. I. (2013) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/01.med.0000433055.99570.52 · Cited by 40
Free Thyroxine and Functional Mobility, Fitness, and Fatigue in Euthyroid Older Men and Women in the Baltimore Longitudinal Study of Aging
Simonsick, E. M., Chia, C. W., Mammen, J. S., Egan, J. M., & Ferrucci, L. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glv226 · Cited by 38
Thyroglobulin Antibodies are Associated with Symptom Burden in Patients with Hashimoto’s Thyroiditis: A Cross-Sectional Study
Barić, A., Brčić, L., Gračan, S., Škrabić, V., Brekalo, M., Šimunac, M., Lovrić, V. T., Anić, I., Barbalić, M., Zemunik, T., et al. (2018) · Immunological Investigations · doi:10.1080/08820139.2018.1529040 · Cited by 39
Derivation of a multivariate reference range for pituitary thyrotropin and thyroid hormones: diagnostic efficiency compared with conventional single-reference method
Hoermann, R., Larisch, R., Dietrich, J. W., & Midgley, J. E. M. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0031 · Cited by 37
Italian association of clinical endocrinologists statement-replacement therapy for primary hypothyroidism: a brief guide for clinical practice
Guglielmi, R., Frasoldati, A., Zini, M., Grimaldi, F., Gharib, H., Garber, J. R., & Papini, E. (2016) · Endocrine Practice · doi:10.4158/ep161308.or · Cited by 39
Age-Specific Reference Intervals for Thyroid-Stimulating Hormones and Free Thyroxine to Optimize Diagnosis of Thyroid Disease
Jansen, H. I., Dirks, N. F., Hillebrand, J. J., ten Boekel, E., Brinkman, J. W., Buijs, M. M., Demir, A. Y., Dijkstra, I. M., Endenburg, S. C., Engbers, P., et al. (2024) · Thyroid · doi:10.1089/thy.2024.0346 · Cited by 38
“5 However, an increase in mean FT4 concentration varying from 0.26 pmol/L over 13 years and 4.5 pmol/L over 6.5 years of follow-up were reported as well at an older age (age at baseline around 70 years).”
Influential
Thyroid hormones associate with risk of incident chronic kidney disease and rapid decline in renal function: a prospective investigation
Huang, X., Ding, L., Peng, K., Lin, L., Wang, T., Zhao, Z., Xu, Y., Lu, J., Chen, Y., Wang, W., et al. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-1081-8 · Cited by 35
“It might be partially due to the reduced sensitivity of pituitary with the increasing age; and then high FT4 levels could not generate negative feedback to TSH and suppress secretion of TSH [32, 34].”
Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality
Mammen, J. S., McGready, J., Ladenson, P. W., & Simonsick, E. M. (2017) · Thyroid® · doi:10.1089/thy.2017.0211 · Cited by 34
“Regression to the mean has also been reported by Bremner et al . for those with lower TSH (24) and by Pearce et al . for those with higher TSH levels (25).”
Defective erythropoiesis caused by mutations of the thyroid hormone receptor α gene
Park, S., Han, C. R., Park, J. W., Zhao, L., Zhu, X., Willingham, M. C., Bodine, D. M., & Cheng, S.-Y. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006991 · Cited by 36
Age May Influence the Impact of TRAbs on Thyroid Function and Relapse-Risk in Patients With Graves Disease
Bano, A., Gan, E. H., Addison, C., Narayanan, K., Weaver, J. U., Tsatlidis, V., & Razvi, S. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01738 · Cited by 34
“Even in euthyroid persons, older age has been related to increasing circulating TSH without substantial changes in FT4 concentrations (21).”
Background
Progesterone therapy increases free thyroxine levels—data from a randomized placebo‐controlled 12‐week hot flush trial
Sathi, P., Kalyan, S., Hitchcock, C. L., Pudek, M. R., & Prior, J. C. (2012) · Clinical Endocrinology · doi:10.1111/cen.12128 · Cited by 34
Thyrotropin Versus Age Relation as an Indicator of Historical Iodine Intake
van de Ven, A. C., Netea-Maier, R. T., Smit, J. W. A., Kusters, R., van der Stappen, J. W. J., Pronk-Admiraal, C. J., Buijs, M. M., Schoenmakers, C. H. H., Koehorst, S. G. A., de Groot, M. J. M., et al. (2015) · Thyroid · doi:10.1089/thy.2014.0574 · Cited by 33
“It has been previously hypothesized that there is a change of the pituitary TSH set point in the elderly and higher FT 4 levels do not cause the same TSH suppression as in younger individuals (4,5).”
Influential
Prevalence of treated hypothyroidism in the community: Analysis from general practices in North‐East England with implications for the United Kingdom
Ingoe, L. E., Phipps, N., Armstrong, G., Rajagopal, A., Kamali, F., & Razvi, S. (2017) · Clinical Endocrinology · doi:10.1111/cen.13440 · Cited by 35
Expert consensus on diagnosis and treatment for elderly with thyroid diseases in China (2021)
Liu, Y., Shan, Z., & Endocrine Metabolic Diseases Group of the Chinese Geriatrics Society (2021) · Aging Medicine · doi:10.1002/agm2.12165 · Cited by 33
Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid
Cho, B. A., Yoo, S., Song, Y. S., Kim, S., Lee, K. E., Shong, M., Park, Y. J., & Seo, J. (2018) · Thyroid · doi:10.1089/thy.2017.0359 · Cited by 35
Ft3 is Higher in Males than in Females and Decreases Over the Lifespan
Strich, D., Karavani, G., Edri, S., Chay, C., & Gillis, D. (2017) · Endocrine Practice · doi:10.4158/ep171776.or · Cited by 32
Thyroid And Aging
Jasim, S., & Gharib, H. (2017) · Endocrine Practice · doi:10.4158/ep171796.ra · Cited by 35
Associations between thyroid function and mortality: the influence of age
van de Ven, A. C., Netea-Maier, R. T., de Vegt, F., Ross, H. A., Sweep, F. C. G. J., Kiemeney, L. A., Smit, J. W., Hermus, A. R., & den Heijer, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-1070 · Cited by 31
“Clinical Study A C van de Ven and others Thyroid function and mortality 171 :2 above the upper limit of the currently used reference range (29, 38, 39).”
Hypothyroidism after hemithyroidectomy: a systematic review and meta-analysis
Cooper, D., Kaur, R., Ayeni, F. E., Eslick, G. D., & Edirimanne, S. (2024) · Thyroid Research · doi:10.1186/s13044-024-00200-z · Cited by 33
“Age has been observed to be associated with thyroid decline and elevated TSH levels [76–78], with studies showing a TSH increase of 0.08 mU/L per decade of age [79] which may explain the preponderance of older patients in the hypothyroid group.”
BackgroundInfluential
Reference intervals for thyrotropin in an area of Northern Italy: the Pordenone thyroid study (TRIPP)
Tozzoli, R., D’Aurizio, F., Metus, P., Steffan, A., Mazzon, C., & Bagnasco, M. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0825-0 · Cited by 29
Thyroid Function Reference Intervals by Age, Sex, and Race
Li, Q., Tang, Y., Yu, X., Qin, G., Tian, L., Cheng, L., Lü, Y., Zhao, Z., Liu, L., Zhang, K., et al. (2025) · Annals of Internal Medicine · doi:10.7326/annals-24-01559 · Cited by 29
Aging, Hormones and Receptors
Hill, M., Třískala, Z., Honců, P., Krejčí, M., Kajzar, J., Bičı́ková, M., Ondřejíková, L., Jandová, D., & Sterzl, I. (2020) · Physiological Research · doi:10.33549/physiolres.934523 · Cited by 31
Heterogeneity and Dynamics of Vasculature in the Endocrine System During Aging and Disease
Stücker, S., Angelis, J. E. D., & Kusumbe, A. P. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.624928 · Cited by 32
Draft of Russian Clinical Practice Guidelines «Male hypogonadism»
Dedov, I. I., Mokrysheva, N. G., Mel'nichenko, G. A., Rozhivanov, R. V., Kamalov, A. A., Mkrtumyan, A. M., Khalimov, Y. S., & Ворохобина, Н. В. (2022) · Obesity and metabolism · doi:10.14341/omet12817 · Cited by 32
Thyroid function tests and early outcomes of acute ischemic stroke in older euthyroid patients
Forti, P., Maioli, F., Coveri, M., Nativio, V., Arnone, G., Loreti, A., Zoli, M., Sacquegna, T., & Procaccianti, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.11.011 · Cited by 29
“Possible explanations for these changes include age-related alteration in the hypothalamic-pituitary set point for TSH because of diminished sensitivity to negative feed-back, a decrease in TSH bioactivity, decreased responsiveness of the thyroid gland, or alterations in the clearance of peripheral thyroid hormones (B…”
Influential

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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