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
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Background
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High androgen levels protect against hypothyroidism
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Monitoring the effects of iodine prophylaxis in the adult population of southern Italy with deficient and sufficient iodine intake levels: a cross-sectional, epidemiological study
Bonofiglio, D., Catalano, S., Perri, A., Santoro, M., Siciliano, L., Lofaro, D., Gallo, M., Marsico, S., Bruno, R., Giordano, C., et al. (2017) · British Journal Of Nutrition · doi:10.1017/s0007114516004499 · Cited by 10
Age-related change in thyroid-stimulating hormone: a cross-sectional study in healthy euthyroid population
Chen, J., Zhou, W., Pan, F., Cui, W., Li, M., & Hu, Y. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej18-0113 · Cited by 10
Subclinical Hypothyroidism: is it Really Subclinical with Aging?
Gourmelon, R., Donadio, S., Chikh, K., Rabilloud, M., Kuczewski, E., Gauchez, A., Charrié, A., Brard, P.-Y., Andreani, R., Bourre, J. C., et al. (2018) · Aging and Disease · doi:10.14336/ad.2018.0817 · Cited by 12
“Elevated TSH level which is not on line with T3 and T4 levels together with hCS could be indicative of reduced bioactivity of TSH (22, 25, 41).”
Background
Age-Related Serum Thyroid-Stimulating Hormone Reference Range in Older Patients Treated with Levothyroxine: A Randomized Controlled Feasibility Trial (SORTED 1)
Razvi, S., Ryan, V., Ingoe, L. E., Pearce, S. H. S., & Wilkes, S. (2019) · European Thyroid Journal · doi:10.1159/000504047 · Cited by 11
Endocrinology and Aging
Lamberts, S. W. J., & van den Beld, A. W. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00027-7 · Cited by 10
Thyrotropin reference interval in older adults
Zhai, X., Li, Y. J., Teng, X., Teng, W., Shi, X., & Shan, Z. (2024) · Endocrine Connections · doi:10.1530/ec-24-0435 · Cited by 9
“There was a 13% increase in TSH (55) or a mean TSH change of 0.32 mIU/L (9) over the 13-year period.”
Influential
Considerations in the Diagnosis and Management of Thyroid Dysfunction in Older Adults
Jasim, S., & Papaleontiou, M. (2025) · Thyroid · doi:10.1089/thy.2025.0128 · Cited by 13
Association of Thyroid-Stimulating Hormone with Resting Energy Expenditure in Euthyroid Elderly Subjects: A Cross-Sectional Study
Nagel, A., Spinneker, A., & Neuhäuser‐Berthold, M. (2015) · Annals of Nutrition and Metabolism · doi:10.1159/000441625 · Cited by 9
Influence of Smoking on Thyroid Function in Japanese Subjects: Longitudinal Study for One Year of On-Off Smoking
Nakajima, Y., Yamada, S., Nishikido, A., Katano-Toki, A., Ishida, E., Akuzawa, M., Sakamaki, K., Yamada, E., Saito, T., Ozawa, A., et al. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00155 · Cited by 9
“TSH level against thyroid hormone level or reductions in the biological activity of serum TSH [5].”
Background
Thyroid stimulating hormone values of clinical decisions of hypothyroidism measurement by three different automated immunoassays
Mirjanić-Azarić, B., Jerin, A., & Savic, Z. R. (2019) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2019.1703215 · Cited by 9
The reference intervals for thyroid hormones: A four year investigation in Chinese population
Xie, T., Su, M., Feng, J., Pan, X., Wang, C., & Tang, T. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1046381 · Cited by 9
Higher free thyroxine levels are associated with sarcopenia in elderly Koreans
Choi, Y. J., Lee, Y., Kim, K., Park, S.-E., & Chung, Y. (2015) · Osteoporosis and Sarcopenia · doi:10.1016/j.afos.2015.11.001 · Cited by 9
Pattern and factors associated with cardiovascular diseases among patients attending the cardiac center in Arar City, Northern Saudi Arabia
Altaleb, F. F., Alshammari, O. M., Alanazi, H. M. H., Aljaber, D. A., Alanazi, A. B., El-Fetoh, N. M. A., Mohammed, N. A., & Aljaber, H. A. A. (2017) · Electronic physician · doi:10.19082/5459 · Cited by 9
“The latter study was conducted among the elderly population and this may explain the higher rates revealed by this study as the prevalence of hypothyroidism shows a significant increase in the older age classes (21).”
Result
Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men
van der Spoel, E., Roelfsema, F., & van Heemst, D. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab075 · Cited by 8
Reference intervals for thyroid-stimulating hormone, free thyroxine, free triiodothyronine, and total triiodothyronine in the Lebanese adult population
Salameh, C., Achkar, A. A., Boustany, J. E., Sleilaty, G., & Gannagé‐Yared, M. (2022) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/00045632221077865 · Cited by 8
Age-associated increase of thyroid hormone receptor β gene promoter methylation coexists with decreased gene expression
Pawlik-Pachucka, E., Budzińska, M., Wicik, Z., Domaszewska-Szostek, A., Owczarz, M., Roszkowska-Gancarz, M., Gewartowska, M., & Puzianowska‐Kuźnicka, M. (2018) · Endocrine Research · doi:10.1080/07435800.2018.1469648 · Cited by 7
Low-Normal Thyroid Function Predicts Incident Anemia in the General Population With Euthyroid Status
Gu, Y., Quynh, V. T., Zhang, Q., Liu, L., Meng, G., Wu, H., Bao, X., Zhang, S., Sun, S., Wang, X., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00888 · Cited by 7
Multinational Survey of Treatment Practices of Clinicians Managing Subclinical Hypothyroidism in Older People in 2019
Razvi, S., Arnott, B., Teare, M. D., Hiu, S. K. W., O’Brien, N., & Pearce, S. H. S. (2020) · European Thyroid Journal · doi:10.1159/000509228 · Cited by 9
Iodine deficiency is associated with increased thyroid hormone sensitivity in individuals with elevated TSH
Sun, Y. J., Teng, D., Zhao, L., Shi, X., Li, Y., Shan, Z., & Teng, W. (2022) · European Thyroid Journal · doi:10.1530/etj-21-0084 · Cited by 8
The Prevalence of Subclinical Hypothyroidism in the Population of Elderly Nursing Home Residents in Zagreb
Jukić, T. (2022) · Acta Clinica Croatica · doi:10.20471/acc.2022.61.01.05 · Cited by 10
“Age (yrs) 45 (19-55) 42 (23-53) 45 (19-55) 72 (60-92) 67 (60-89) 71 (60-92)”
Age and Assay Related Changes of Laboratory Thyroid Function Tests in the Reference Female Population
Barhanovic, N. G., Antunović, T., Kavarić, S., Djogo, A., & Spasojevic, V. K. (2018) · Journal of Medical Biochemistry · doi:10.2478/jomb-2018-0020 · Cited by 8
“The results of our investigation are consistent with some other previously conducted large population studies in areas with adequate iodine supplementation (6, 22, 24), showing that the median, lower and upper reference limits of the serum thyrotropin values of female subjects continuously increased with age.”
BackgroundResult
Age moderates the associations between TRAbs, free T3 and outcomes of Graves’ disease patients with radioactive iodine treatment
Lu, L., Gao, C., & Zhang, N. (2020) · Clinical Endocrinology · doi:10.1111/cen.14301 · Cited by 8
Associations of thyroid hormones with chronic diarrhea and constipation in euthyroid individuals
Zeng, W., Wang, Y., & Zhang, L. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1395743 · Cited by 7
The Effects of Elaeagnus angustifolia L. on the Thyroid-Stimulating Hormone, Dehydroepiandrosterone-Sulfate, Prolactin and Cortisol Levels in Post-Menopausal Women: A Double-Blind, Randomized, and Placebo-Controlled Study
Jalalvand, F., Rezaei, A., Badehnoosh, B., Yaseri, M., Qorbani, M., Emaminia, F., & Shabani, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.654459 · Cited by 7
“In addition to levels of thyroid hormones, particularly free T4, other studies are needed to define an age-specific TSH reference range as part of clinical practice (Bremner et al., 2012; Leng and Razvi, 2019).”
Background
Changes in thyroid function with age: results from the Pizarra population-based longitudinal study
Lago-Sampedro, A. M., Gutiérrez‐Repiso, C., Valdés, S., Maldonado, C., Colomo, N., Almaraz, M. C., Rubio‐Martín, E., Morcillo, S., Esteva, I., de Adana, M. S. R., et al. (2015) · International Journal of Clinical Practice · doi:10.1111/ijcp.12545 · Cited by 7
Stress, relationship satisfaction, and health among African American women: Genetic moderation of effects.
Lei, M., Beach, S. R. H., Simons, R. L., Barr, A. B., Cutrona, C. E., & Philibert, R. A. (2015) · Journal of Family Psychology · doi:10.1037/fam0000140 · Cited by 7
“Therefore, some scholars (Bremner et al., 2012; Whisman et al., 2010) have attempted to incorporate biomarkers as indicators of physiological stress.”
The hypothalamic-pituitary-thyroid axis and personality in a sample of healthy subjects
Пискунов, А. К., Escolano, A. F., Teryaeva, N. B., Moshkin, A., & Rodríguez, J. R. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.10.023 · Cited by 7
Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS)
Amouzegar, A., Dehghani, M., Abdi, H., Mehran, L., Masoumi, S., & Azizi, F. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01876-6 · Cited by 7
“The elderly individuals with SCH tend to persist in this condition; the higher TSH level in old individuals might be due to reduced TSH bioactivity and alteration in TSH set point as a physiological adaptation rather than thyroid disease that must be considered as an important factor in interpreting the results of stu…”
Background
Thyroid Disorders in the Elderly
Higgins, K. M. (2018) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2018.01.011 · Cited by 6
Age-related thyroid hormone resistance: A friend or foe
Mooradian, A. D. (2023) · Endocrine and Metabolic Science · doi:10.1016/j.endmts.2023.100132 · Cited by 6
Ultrasonographic assessment of thyroid volume in oldest-old individuals
Duarte, G. C., Araújo, L. M. Q., Filho, F. M., Filho, C. D. M. A., & Cendoroglo, M. S. (2016) · Archives of Endocrinology and Metabolism · doi:10.1590/2359-3997000000223 · Cited by 6
“Although there has been an increasing prevalence of thyroid disorders in elderly individuals (25,26), most population studies have failed to dedicate exclusive attention to individuals aged 80 years or older.”
Background
Hypothyroidism Treatment Among Older Adults: Evidence from a Claims Database
Lage, M. J., Espaillat, R., Vora, J. B., & Hepp, Z. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01296-z · Cited by 6
Complex environmental contaminant mixtures and their associations with thyroid hormones using supervised and unsupervised machine learning techniques
Liberda, E. N., Zuk, A. M., Di, D. S., Moriarity, R. J., Martin, I., & Tsuji, L. J. S. (2021) · Environmental Advances · doi:10.1016/j.envadv.2021.100054 · Cited by 6
Transient high thyroid stimulating hormone and hypothyroidism incidence during follow up of subclinical hypothyroidism
Abu-Helalah, M. A., Alshraideh, H. A., Al-Sarayreh, S. A., & Alhader, A. A. (2021) · Endocrine Regulations · doi:10.2478/enr-2021-0022 · Cited by 6
“32 mIU/L over 13 years) with no significant change in FT4 concentrations with aging (Bremner et al. 2012).”
BackgroundResultInfluential

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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