Prevalence and Risk Factors of Thyroid Dysfunction in Older Adults in the Community

Prevalence estimates and evidence informing treatment targets for thyroid dysfunction largely come from studies of middle-aged adults. We conducted a cross-sectional analysis to determine the prevalence of thyroid dysfunction and risk factors for abnormal thyroid tests in participants aged ≥65 in the Atherosclerosis Risk in Communities (ARIC) study (N = 5,392). We measured serum concentrations of triiodothyronine (T3), free thyroxine (FT4), thyroid peroxidase antibody (Anti-TPO), and thyroid stimulating hormone (TSH). In this population (58% women, 22% black), 17% reported medication use for thyroid dysfunction. Among those not on treatment, the prevalence of overt and subclinical hypothyroidism was 0.82% and 6.06%, respectively. Overt and subclinical hyperthyroidism affected 0.26% and 0.78%, respectively. Multivariable adjusted TSH, FT4 and T3 levels were 25%, 1.3% and 3.9% lower in blacks compared to whites, respectively. Men were less likely to be anti-TPO positive compared to women (p < 0.001). Former and never smoking were associated with lower T3 and FT4 levels compared to current smoking. The prevalence of thyroid dysfunction in older adults is nearly 25%. Multiple illnesses can interact to contribute to declines in health. Additional attention to thyroid dysfunction and screening in this age group is recommended.


Results
Among the 5,392 participants, using the ARIC defined (or Roche defined) cut-offs, the prevalence of hypothyroidism was 23.78% (28.90%) and the prevalence of hyperthyroidism was 1.15% (0.36%). Among those with hypothyroidism and hyperthyroidism, 71.06% (56.13%) and 9.68% (30%), respectively, were treated previously. The prevalence of overt hypothyroidism in untreated participants was 0.82% (2.21%), subclinical hypothyroidism was 6.06% (10.5%), overt hyperthyroidism was 0.26% (0.07%), subclinical hyperthyroidism was 0.78% (0.18%) and euthyroidism was 75.07% (70.74%). The prevalence of participants with treated hypothyroidism or hyperthyroidism was 16.90% (16.22%) and 0.11% (0.11%) respectively (Table 1). Significant differences in prevalence of thyroid dysfunction were observed across participant characteristics. Women had a higher prevalence of treated hypothyroidism compared to males (P < 0.001). Subclinical hypothyroidism and treated hypothyroidism were significantly greater in whites compared to blacks (P < 0.001), while prevalence of subclinical hyperthyroidism was greater in blacks compared to whites (P = 0.002). Higher age and BMI were significantly associated with higher prevalence of subclinical hypothyroidism (P = 0.008 and 0.004 respectively) and treated hypothyroidism (P = 0.001 and 0.049 respectively) ( Table 1).  show the prevalence of thyroid dysfunction categories by race and age group. Across each age group, the prevalence of subclinical hypothyroidism was higher in whites compared to blacks, with the highest prevalence found in the oldest age group (Fig. 2). The opposite trend was observed for subclinical hyperthyroidism, in which prevalence was greater in blacks compared to whites at any given age group (Fig. 4). No clear racial differences were observed for untreated overt hypothyroidism and untreated overt hyperthyroidism (Figs 1, 3).
In adjusted analyses, TSH levels in black individuals, on average, were 24.7% lower compared to whites (P < 0.001) after adjusting for sex, age, BMI, smoking and drinking history, physical activity and anti-TPO positivity (Table 2). Racial differences were also observed with FT4 and T3, in which levels were 1.32% (P = 0.023) and 3.89% (P < 0.001) lower in blacks compared to whites, respectively. Both FT4 and T3 were associated with sex, with levels 1.25% (P = 0.009) and 1.75% (P = 0.001) lower in men compared to women respectively. There were no significant independent differences in TSH by sex.
Of all three blood tests, T3 was most strongly associated with age, with levels up to 6.6% lower in individuals older than 80 years of age compared to those ages 65-70. A clear association with age was not observed for FT4. TSH on the other hand, was positively associated with age, with levels up to 9.1% higher in individuals >80 years-old compared to 65-70 years-old (P = 0.003) ( Table 2). T3 levels were 3.5% higher in overweight or obese individuals compared to individuals with a normal BMI. By contrast, FT4 was lower at higher BMI categories. No statistically significant association was observed between TSH and BMI after adjustment.
Smoking status was significantly associated with TSH, FT4, and T3 levels. Current smokers had lower TSH levels compared to former or never smokers (P < 0.001). An inverse relationship was observed for FT4 and T3, in which current smokers had higher levels compared to former or never smokers (P < 0.001). We did not observe an association of TSH or FT4 with drinking history, although T3 levels were lower for current drinkers as compared to never or former drinkers (P < 0.001) ( Table 2). We observed sex differences in anti-TPO positivity. Men were much less likely to be auto-antibody

Discussion
In this study, we assessed the prevalence of thyroid dysfunction, and the associations of TSH, FT4, T3 levels and anti-TPO positivity with various demographic and clinical risk factors. Our study has the following important findings: (1) the prevalence of thyroid dysfunction in an older age population was nearly 25% when accounting for treated and untreated thyroid dysfunction categories, (2) significant sex and racial differences were observed in subclinical hypothyroidism, subclinical hyperthyroidism, and treated hypothyroidism in this age group, (3) significantly lower TSH, FT4 and T3 levels were observed in older males and older black individuals, and 4) thyroid hormone levels were associated with clinical risk factors including smoking history, and BMI category.
Data from the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994 in individuals aged 12 and older and representative of the general U.S. population found that approximately 4.6% had undiagnosed hypothyroidism (0.3% clinical and 4.3% subclinical) and 1.3% had undiagnosed hyperthyroidism (0.5% clinical and 0.7% subclinical). This survey also observed the prevalence of anti-TPO positivity and TSH concentrations to be greater in females, increase with age, and greater in whites and Mexican Americans compared to blacks 10 . In our study of an older population, we observed a higher prevalence of undiagnosed hypothyroidism (6.88%, 0.82% overt and 6.06% subclinical) and a smaller prevalence of undiagnosed hyperthyroidism (1.04%, 0.26% overt and 0.78% subclinical). We did observe higher levels of TSH in white participants, and men were less likely to have anti-TPO positivity compared to women. Racial disparities in thyroid hormones have been previously reported in the literature 18,21 . Although TSH levels were lower in men compared to women, our results were not significant after adjustment, and only FT4 and T3 demonstrated sex differences in older adults. One explanation for these findings could be related to hormonal action, given that women in our cohort were post-menopausal. Some studies have demonstrated that higher estrogen levels contribute to elevated levels of TSH or lower levels of FT4, resulting in hypothyroid symptoms 22,23 . In our cohort of post-menopausal women, this mechanism would be diminished.
Compared to NHANES, our estimates demonstrated a greater prevalence for all thyroid dysfunction categories (except for overt hyperthyroidism), particularly in subclinical hypothyroidism, which could partly be explained by the older population used in our analysis. Previous studies have demonstrated a higher prevalence of thyroid dysfunction in older individuals 9,24 . One study suggested that with aging, the set point for TSH secretion is altered, resulting in higher serum TSH concentrations due to diminished sensitivity of thyrotropes to negative feedback of thyroid hormones 11 . Other studies demonstrated that if age-adjusted normal ranges are used in older adults, the prevalence of thyroid dysfunction may not increase with old age and some individuals might be reclassified from "abnormal" to "normal", avoiding unnecessary treatment 11,12 . The debate regarding age-specific cut-points for thyroid dysfunction has clinical and economic implications, given the high prevalence in older adults and decreasing TSH threshold levels for treatment over the years 25 .
The strong association between smoking and thyroid hormone levels has been previously demonstrated 17 . In a cross-sectional study of the effect of smoking on TSH levels, serum TSH levels were significantly lower in current smokers than in non-smokers 17 . Similar to these findings, we observed significantly lower levels of TSH, and higher levels of FT4 and T3 in current smokers compared to never or former smokers. Lower serum TSH levels have also been observed in active smokers in the NHANES III study 15 . While the mechanism for an association of smoking with thyroid hormone levels is unknown, one proposed explanation is that nicotine's effect on sympathetic activation could enhance thyroid hormone secretion 17 . If causal, smoking in older adults may be an important consideration when deciding on initiating or changing thyroid hormone therapy, given that higher levels of FT4 and T3 could change treatment decisions.
Limitations of our study include the cross-sectional design, while ideal for establishing prevalence, we are unable to establish temporality of the observed risk factor associations. Furthermore, this study does not account for the general variability of thyroid function tests in an individual, and there is a possibility that some patients with transient thyroid function tests changes have been misclassified due to the cross-sectional design. As our study used a community-based population, power was limited for some analyses, especially for hyperthyroidism (n = 56 in our study population). Although we adjusted for multiple demographic and clinical risk factors in our analyses, as with any observational study, residual confounding may be a concern. Our study demonstrated a high prevalence of thyroid dysfunction in an older, community-based population, which is higher than the previously reported prevalence of thyroid dysfunction in community-based studies with younger and middle-aged populations. Furthermore, our study demonstrated that the prevalence of undiagnosed hypothyroidism in older individuals is higher than what has previously been reported. There were clear differences by sex and race, with older women having a higher prevalence of treated hypothyroidism compared to older men, and older whites having a higher prevalence of subclinical hypothyroidism and treated hypothyroidism compared to older blacks. The prevalence of subclinical hyperthyroidism was greater in blacks compared to whites.
With rising life expectancies and aging populations, it is increasingly important to understand variations in thyroid dysfunction in older individuals and their association with risk factors encountered in daily clinical practice. Our study demonstrated a thyroid dysfunction prevalence of nearly 25% in older individuals. This high prevalence sheds a light on the potential for the underappreciation of both overt and subclinical thyroid diseases, which can have substantial effects on the management and treatment of older patients who might also present with other complex comorbidities. Our results call for greater awareness of thyroid dysfunction, and the potential need for more thyroid function screening in this age group.

Methods
We conducted a cross-sectional study using data from the Atherosclerosis Risk in Communities (ARIC) study. This is a prospective epidemiologic cohort that began with 15,792 individuals recruited between 1987-1989 from 4 study centers in the United States (Forsyth County, North Carolina, Jackson, Mississippi, Minneapolis, Minnesota, and Washington County, Maryland) 26 . The current study involves visit 5 (2011-2013). All study participants provided informed consent at each study visit.