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

School of Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 02/2012; 97(5):1554-62. DOI: 10.1210/jc.2011-3020
Source: PubMed


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.
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.
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.
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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    • "These results are in accordance with previously published data on mobility in elderly individuals [9, 32]. Several studies have presented evidence supporting a change in the distribution of the serum TSH normality curve according to age, with a shift to higher values for very old individuals [16, 17, 49, 50]. This change, underlain by genetic factors, modifications in central set-point for thyroid hormone feed-back, and dietary iodine supply, would provide better guidance for further evaluation of thyroid dysfunction and would reflect growing support for the assumption that minimally elevated serum TSH levels in elderly subjects should be considered normal [16, 17, 49, 50]. "
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    ABSTRACT: This study aimed to evaluate the prevalence of thyroid dysfunction in elderly subjects attending an outpatient clinic at a tertiary hospital and to assess whether subclinical hypothyroidism (SCH) or aging affected activities of daily living (ADLs), instrumental activities of daily living (IADLs), cognitive status, or depressive symptoms. This crosssectional study included 411 patients recruited in the outpatient geriatric setting. 48 subjects reported levothyroxine use and were evaluated separately. After excluding subjects with diseases or drugs which could influence thyroid status, the 284 subjects remaining were classified as having euthyroidism (n = 235, 82.8 %), subclinical hypothyroidism (n = 43, 15.1 %), subclinical hyperthyroidism (n = 4, 1.4 %), or overt hyperthyroidism (n = 2, 0.7 %). ADLs and IADLs were assessed using the Katz Index (ranging from 0 [independence] to 6 [dependence in all activities]) and Health Assessment Questionnaire (ranging from 0 to 3 [severely disabled]), respectively. Cognition was assessed using the mini mental state depressive symptoms that were assessed using the Geriatric depression scale or cornell scale for depression in dementia. SCH did not reduce performance in ADLs or IADLs in elderly subjects as a whole, but was an independent protective factor against dependence in ADLs (OR = 0.196 [0.045-0.853]; p = 0.003) and IADLs (OR = 0.060 [0.010-0.361]; p = 0.002) in subjects aged ≥85 years. Very old subjects with SCH showed better performance in ADLs than did those with euthyroidism (Katz Index: 0.9 ± 1.6 [median: 0.5] vs. 1.7 ± 1.7 [1.0], p = 0.024; HAQ: 1.2 ± 0.8 [0.9] vs. 1.8 ± 1.0 [1.9], p = 0.015). This putative protective effect of SCH was not found in subjects aged <85 years. The number of falls, number of medications used, depressive symptoms, and cognitive impairment did not differ among thyroid status groups, regardless of age. In conclusion, SCH does not have impact functional performance in the elderly population as a whole, but was associated with better functional status in subjects aged ≥85 years.
    Endocrine 11/2013; 47(1). DOI:10.1007/s12020-013-0077-x · 3.88 Impact Factor
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    • "The Shire has been the site of repeated cross-sectional surveys of adults from 1966 to 2009, with participation rates ranging from 64 to 91% [13]. Health surveys have previously focused on specific systems or diseases: respiratory [14,15]; cardiovascular [16-18]; gastrointestinal [19]; endocrine [20]; iron metabolism [21,22]; cancer mortality [23]; the “metabolic syndrome” [24]; dementia and diabetes [25] and genetic epidemiology [13,26-28]. "
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    ABSTRACT: The global trend of increased life expectancy and increased prevalence of chronic and degenerative diseases will impact on health systems. To identify effective intervention and prevention strategies, greater understanding of the risk factors for and cumulative effects of chronic disease processes and their effects on function and quality of life is needed.The Busselton Healthy Ageing Study aims to enhance understanding of ageing by relating the clustering and interactions of common chronic conditions in adults to function. Longitudinal (3--5 yearly) follow-up is planned.Methods/design: Phase I (recruitment) is a cross-sectional community-based prospective cohort study involving up to 4,000 'Baby Boomers' (born from 1946 to 1964) living in the Busselton Shire, Western Australia. The study protocol involves a detailed, self-administered health and risk factor questionnaire and a range of physical assessments including body composition and bone density measurements, cardiovascular profiling (blood pressure, ECG and brachial pulse wave velocity), retinal photography, tonometry, auto-refraction, spirometry and bronchodilator responsiveness, skin allergy prick tests, sleep apnoea screening, tympanometry and audiometry, grip strength, mobility, balance and leg extensor strength. Cognitive function and reserve, semantic memory, and pre-morbid intelligence are assessed. Participants provide a fasting blood sample for assessment of lipids, blood glucose, C-reactive protein and renal and liver function, and RNA, DNA and serum are stored. Clinically relevant results are provided to all participants. The prevalence of risk factors, symptoms and diagnosed illness will be calculated and the burden of illness will be estimated based on the observed relationships and clustering of symptoms and illness within individuals. Risk factors for combinations of illness will be compared with those for single illnesses and the relation of combinations of illness and symptoms to cognitive and physical function will be estimated. This study will enable a thorough characterization of multiple disease processes and their risk factors within a community-based sample of individuals to determine their singular, interactive and cumulative effects on ageing. The project will provide novel cross-sectional data and establish a cohort that will be used for longitudinal analyses of the genetic, lifestyle and environmental factors that determine whether an individual ages well or with impairment.
    BMC Public Health 10/2013; 13(1):936. DOI:10.1186/1471-2458-13-936 · 2.26 Impact Factor
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    • "Consequently, the authors have suggested that age-based reference ranges for TSH should be considered [18]. Moreover, a recent longitudinal study from Western Australia (Busselton survey), for the first time, showed that serum TSH increases (mean increase of 0.32 mU/L over 13 years) with no significant change in free T4 concentrations with aging [19]. Similarly, another longitudinal thyroid function evaluation in a very elderly subgroup (mean age 85 years) of the Cardiovascular Health Study (All Stars Study) found that serum TSH increased by 13% over an average of 13 years of follow-up associated with a 1.7% increase in FT4 and a 13% reduction in total T3 levels [20]. "
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    ABSTRACT: Thyroid hormone production, metabolism, and action change with aging. The reference ranges for serum thyrotropin and thyroid hormones are derived mainly from younger populations. Thus, the prevalence of subclinical thyroid dysfunction is increased greatly in the elderly. However, it is unclear whether mild thyroid dysfunction in the elderly is associated with adverse outcomes. In this review, we discuss current evidence-based literature on thyroid function in the elderly and whether subclinical thyroid dysfunction in the elderly should be treated.
    Journal of Thyroid Research 09/2013; 2013:481287. DOI:10.1155/2013/481287
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