Relationship Between Circulating Thyroid‐Stimulating Hormone, Free Thyroxine, and Free Triiodothyronine Concentrations and 9‐Year Mortality in Euthyroid Elderly Adults

Abstract

Objectives Thyroid dysfunction in the elderly is associated with adverse clinical outcomes, with mortality being associated with low TSH. However, it is still unknown whether variability of thyroid function test within the reference range is associated with mortality in older adults. We studied the association between plasma levels of TSH, free T3 (FT3), and free T4 (FT4), and all-cause mortality in older adults who had all three hormones within the normal range. Design Longitudinal study Setting Community-based Participants Total of 815 euthyroid participants of the InCHIANTI study, aged 65 years or older Measurements All subjects had TSH, FT3, and FT4 within the reference range at baseline. Plasma TSH, FT3 and FT4 were predictors and 9-year all-cause mortality was the outcome. Cox proportional hazards models adjusted for confounders were used to examine the relationship between quartiles of TSH, FT3, and FT4 and all-cause mortality over 9 years of follow-up. Results During the follow-up (mean persons-years 8643.74 [min-max, 35.36-16985.00]), 181 deaths occurred (22.2%). Participants with TSH in the lower quartile had higher mortality than the rest of the population. After adjusting for multiple confounders, participants with TSH in the lowest quartile (Hazard Ratio: 2.22; 95% Confidence Interval: 1.19–4.22) had significantly higher all-cause mortality than those with TSH in the highest quartile. Neither FT3 nor FT4 were associated with mortality. Conclusions In euthyroid elderly subjects, normal-low TSH represents an independent risk factor for all-cause mortality.

Thyroid status and mortality in nonagenarians from long-lived families and the general population

“…A higher BMI was found to be causally related to higher circulating levels of fT3 [ 19 ], and higher BMI has also been positively associated with old age survival [ 20 ]. The lower risk of mortality with higher levels of fT3 we found was reported by others only in crude analyses when illness was not taken into account [ 18 , 21 , 22 ]. Yet, adjustment for levels of hsCRP did not materially influence the results.…”

Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study

“…In contrast with subclinical hypothyroidism, many previous studies have shown that low serum TSH is associated with poor outcomes, either increased all-cause or vascular mortality, or AF (12–14, 17, 29, 36, 37). This has led to suggestions that patients with low TSH should be aggressively treated for hyperthyroidism to avoid these complications despite a complete lack of compelling (level 1) evidence to support the effectiveness of this strategy (1, 41, 42).…”

“…The most frequent abnormality found is a raised serum TSH with circulating thyroid hormone concentrations that are within reference range, correlating with the state of subclinical hypothyroidism, and some studies suggest an adverse effect of this state (8, 10, 22, 24) whereas others show a neutral or even protective effect on outcome (2, 17, 25, 29, 36, 37). Notably, the Leiden 85+ study, a cohort study of 85-year-olds with a similar design to our study, found that subclinical hypothyroidism was associated with reduced all-cause mortality and cardiovascular mortality (29).…”

Elevated TSH in adults treated for hypothyroidism is associated with increased mortality

“…Exploring the minimal and average TSH levels during follow-up proved a similar trend. Although several studies investigated the effects of subclinical and overt hypothyroidism on mortality, and others investigated the significance of single measurement of thyroid function tests, this is the first study to focus on levothyroxine-treated adult patients with repeated measurements of thyroid function tests (4,6,7,8,9,10,11,12,13,14,15,16,17) (Table 3).…”

“…Numerous studies investigated the link between subclinical and overt hypothyroidism and mortality, with conflicting results (4,6,7,8,9,10,11,12,13,14,15,16,17). Waring et al reported that a single measurement of thyroidstimulating hormone (TSH) and free T4 (fT4) did not predict the mortality in older men (7).…”