Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort
ABSTRACT 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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ABSTRACT: Context: The appropriateness of current reference ranges for thyroid function testing in older adults has been questioned. Objective: To determine the relationship between thyroid function tests within the euthyroid range and adverse outcomes in older adults not taking thyroid medication. Design, Setting, and Participants: 2843 US community-dwelling adults aged ≥ 65 years enrolled in the Cardiovascular Health Study with TSH, free T4 (FT4), and total T3 concentrations in the euthyroid range Main Outcome Measures: Incidence of atrial fibrillation, coronary heart disease, heart failure, hip fracture, dementia, and all-cause death Results: No departures from linearity were detected. Higher TSH was negatively associated (p=0.03) and higher FT4 was positively associated (p=0.007) with mortality. Higher FT4 was associated with atrial fibrillation (p<0.001) and heart failure (p=0.004). Compared with the first quartile, individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia (p<0.05) and those with FT4 in the fourth quartile had higher incidences of atrial fibrillation, coronary heart disease, heart failure and mortality (11.0, 8.0, 7.8, and 14.3 per 1000 person-years, respectively, all p <0.05). Total T3 was not associated with any outcome. Conclusions: Higher TSH and lower FT4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events in older people, including mortality. This suggests tolerance for lower thyroid hormone levels in this age group. Clinical trials are needed to evaluate the risk-benefit profile of new thresholds for initiating treatment and optimal target concentrations for thyroid hormone replacement in older people.Journal of Clinical Endocrinology & Metabolism 12/2014; 100(3):jc20143586. DOI:10.1210/jc.2014-3586 · 6.31 Impact Factor
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ABSTRACT: Abstract Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.The Aging Male 02/2015; 18(1):1-11. DOI:10.3109/13685538.2015.1004049 · 1.85 Impact Factor
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ABSTRACT: Older men have lower circulating testosterone (T) and insulin-like growth factor-I (IGF-I) but higher levels of thyrotrophin (TSH) compared with younger men, and exhibit poorer health. Whether age-associated differences in hormone levels are causally related to cardiovascular disease, or are biomarkers reflecting accumulated ill-health remains under debate. Lower T levels are associated with aortic, peripheral vascular, and cardiovascular disease in middle-aged and older men. In some but not all studies, lower levels of T predict increased incidence of cardiovascular events and mortality. Recently, dihydrotestosterone (DHT) has also been identified as a predictor for peripheral vascular and ischemic heart disease. Small scale randomized clinical trials (RCTs) of T supplementation suggest a protective effect against myocardial ischemia in men with coronary artery disease. There have been no RCTs with the prespecified outcomes of cardiovascular events or mortality. One RCT of T in older men with mobility limitations was stopped due to an excess of cardiovascular adverse events in men receiving T, but other RCTs have not raised similar concerns. Observational studies of testosterone supplementation have reported contrasting results. Levels of IGF-I and its binding proteins 1 and 3 have been variably associated with mortality in some but not all studies, and RCTs of interventions to modulate IGF-I levels are either lacking or lacking in power to examine outcomes of cardiovascular events or mortality. Subclinical hyper- and hypothyroidism predict poorer outcomes, and emerging data implicate higher levels of free thyroxine with other outcomes such as dementia and mortality in older men. However, RCTs that manipulate free thyroxine levels within the normal range are lacking and would be challenging to perform. Further research is needed to clarify the role of these hormones as predictors of cardiovascular outcomes in aging men, and to test whether interventions that modulate levels of T, DHT, IGF-I or free thyroxine would reduce cardiovascular morbidity and mortality.Journal of the American Medical Directors Association 02/2014; 15(5). DOI:10.1016/j.jamda.2013.12.004 · 4.78 Impact Factor