Higher Free Thyroxine Levels Are Associated With Frailty
Higher Free Thyroxine Levels Are Associated With Frailty
Objective Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men.
Design Cross-sectional epidemiological study.
Participants Community-dwelling men aged 70–89 years.
Measurements Circulating thyrotropin (TSH) and free thyroxine (FT4) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results.
Results Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log-linear association of TSH with FT4. There was no association between TSH and frailty. After adjusting for covariates, men with FT4 in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01–1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04–1·79, P = 0·010 for trend). Higher FT4 was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT4 and frailty remained significant when the analysis was restricted to euthyroid men.
Conclusions High-normal FT4 level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men.
Frailty is conceptualised as a deterioration of multiple organ systems, which leads to loss of physiological reserve, diminished capacity to cope with stressors and increased risk of death and disability. The prevalence of frailty increases with increasing age, and preventing the development of frailty in older people would be expected to preserve health and autonomy. One phenotype of frailty can be defined by the presence of three or more of the following five components: unintentional weight loss, exhaustion, poor grip strength, slow walking speed or low physical activity. An alternative method has been proposed using a tool for assessment of frailty, the FRAIL scale. This tool utilises five elements of Fatigue, Resistance, Ambulation, Illnesses and Loss of weight, with frailty represented by the presence of three or more of these elements. This approach to the definition of frailty has been validated against the criteria of subsequent disability and death. However, the underlying mechanisms that contribute to development of frailty as people age remain poorly understood.
Multiple endocrine changes occur during the life course, and some have been implicated in the genesis of frailty. Reduced testosterone levels in older men are associated with frailty and may contribute to fatigue and impairment of muscle function in older men. Insulin-like growth factor-I (IGF-I) is another anabolic hormone that regulates muscle mass, whose level declines with increasing age. There are limited data supporting a potential role for reduced IGF-I in the genesis of frailty in older adults.
Thyroid dysfunction (hyper- or hypothyroidism) is commonly associated with symptoms of fatigue, reduced muscle strength and weight change, with overt symptoms less likely to be recognised in older people. Subclinical hyperthyroidism occurs when circulating thyroid hormone levels are not elevated, but thyrotropin (TSH) levels are suppressed indicating increased pituitary exposure to thyroid hormone. This condition predicts increased risk of cardiovascular events and dysrhythmia. Subclinical hypothyroidism is present when TSH levels are moderately elevated with normal circulating thyroid hormone levels, and with TSH >10 mIU/l, it is associated with increased risk of coronary heart disease.
Recently, it has been recognised that even the small differences in thyroid function that exist between euthyroid subjects may be associated with differences in clinical parameters, including metabolic syndrome, atrial fibrillation, cardiovascular mortality, bone density and the risk of fracture. However, there are few data evaluating the potential contribution of thyroid dysfunction (or differences in thyroid function between euthyroid subjects) to frailty in older persons, particularly men. Identification of differences in thyroid function as a risk factor for frailty would improve understanding of endocrine pathophysiology and provide added opportunities for identifying men at risk of poorer health outcomes. We tested the hypothesis that TSH and/or free thyroxine (FT4) concentrations are associated with frailty in older men.
Abstract and Introduction
Abstract
Objective Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men.
Design Cross-sectional epidemiological study.
Participants Community-dwelling men aged 70–89 years.
Measurements Circulating thyrotropin (TSH) and free thyroxine (FT4) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results.
Results Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log-linear association of TSH with FT4. There was no association between TSH and frailty. After adjusting for covariates, men with FT4 in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01–1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04–1·79, P = 0·010 for trend). Higher FT4 was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT4 and frailty remained significant when the analysis was restricted to euthyroid men.
Conclusions High-normal FT4 level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men.
Introduction
Frailty is conceptualised as a deterioration of multiple organ systems, which leads to loss of physiological reserve, diminished capacity to cope with stressors and increased risk of death and disability. The prevalence of frailty increases with increasing age, and preventing the development of frailty in older people would be expected to preserve health and autonomy. One phenotype of frailty can be defined by the presence of three or more of the following five components: unintentional weight loss, exhaustion, poor grip strength, slow walking speed or low physical activity. An alternative method has been proposed using a tool for assessment of frailty, the FRAIL scale. This tool utilises five elements of Fatigue, Resistance, Ambulation, Illnesses and Loss of weight, with frailty represented by the presence of three or more of these elements. This approach to the definition of frailty has been validated against the criteria of subsequent disability and death. However, the underlying mechanisms that contribute to development of frailty as people age remain poorly understood.
Multiple endocrine changes occur during the life course, and some have been implicated in the genesis of frailty. Reduced testosterone levels in older men are associated with frailty and may contribute to fatigue and impairment of muscle function in older men. Insulin-like growth factor-I (IGF-I) is another anabolic hormone that regulates muscle mass, whose level declines with increasing age. There are limited data supporting a potential role for reduced IGF-I in the genesis of frailty in older adults.
Thyroid dysfunction (hyper- or hypothyroidism) is commonly associated with symptoms of fatigue, reduced muscle strength and weight change, with overt symptoms less likely to be recognised in older people. Subclinical hyperthyroidism occurs when circulating thyroid hormone levels are not elevated, but thyrotropin (TSH) levels are suppressed indicating increased pituitary exposure to thyroid hormone. This condition predicts increased risk of cardiovascular events and dysrhythmia. Subclinical hypothyroidism is present when TSH levels are moderately elevated with normal circulating thyroid hormone levels, and with TSH >10 mIU/l, it is associated with increased risk of coronary heart disease.
Recently, it has been recognised that even the small differences in thyroid function that exist between euthyroid subjects may be associated with differences in clinical parameters, including metabolic syndrome, atrial fibrillation, cardiovascular mortality, bone density and the risk of fracture. However, there are few data evaluating the potential contribution of thyroid dysfunction (or differences in thyroid function between euthyroid subjects) to frailty in older persons, particularly men. Identification of differences in thyroid function as a risk factor for frailty would improve understanding of endocrine pathophysiology and provide added opportunities for identifying men at risk of poorer health outcomes. We tested the hypothesis that TSH and/or free thyroxine (FT4) concentrations are associated with frailty in older men.