Higher Free Thyroxine Levels Predict Increased Incidence of Dementia in Older Men: The Health In Men Study

Abstract

Higher FT(4) levels predict new-onset dementia in older men, independently of conventional risk factors for cognitive decline. Additional studies are needed to explore potential underlying mechanisms and to clarify the utility of thyroid function testing in older men at risk of dementia.

Higher free thyroxine levels are associated with all-cause mortality in euthyroid older men: the Health In Men Study

“…This may reflect reduced sensitivity of the pituitary to T 4 -or liothyronine (T 3 )-mediated suppression of TSH levels, altered TSH bioactivity or reduced thyroid sensitivity to TSH, requiring compensatory elevation of levels to maintain thyroid homeostasis (10). Small differences in thyroid function between euthyroid subjects have been reported to be associated with specific health-related outcomes including atrial fibrillation, reduced bone mineral density and incident dementia (12,13,14). However, the effect of differences in thyroid function in euthyroid older people on the key outcome of mortality remains unclear, with limited available data and inconsistent findings reported (11,15,16,17).…”

MANAGEMENT OF ENDOCRINE DISEASE: l-Thyroxine replacement therapy in the frail elderly: a challenge in clinical practice

“…Even though the group of subjects seropositive for thyroid antibodies had a higher prevalence of abnormal serum TSH concentrations, this inverse correlation persisted after adjusting for TSH values and was therefore independent of TSH (69). A similar lack of association between TSH and frailty was reported in men also (among more than 3000 participants ≥70 years) (70). Simonsick et al showed that older individuals with elevated TSH levels do not demonstrate increased risk of mobility problems; rather, those with mild TSH elevation showed a slight functional advantage (71).…”

“…In a cohort of 3485 euthyroid men aged 70-89 years from the Health In Men Study, higher FT4 levels were found to be associated with all-cause mortality, independently of conventional risk factors and medical comorbidities (76). Noteworthy, in the same cohort from the Health In Men Study, higher FT4 was an independent and significant predictor of frailty, suggesting that circulating FT4, even within the normal range, might contribute to weight loss and reduced physical capability (70). Similar findings had been reported by van den Beld et al who noted that in euthyroid men aged 73-94 years, higher serum FT4 concentrations were associated with reduced physical function, while low serum FT4 was associated with better 4-year survival (77).…”

“…Contrary to expectations, no relationship was found between SHypo and either frailty at baseline or subsequent frail status after a 5-year follow-up (68). Other two cross-sectional studies have assessed the relationship between TSH levels and frailty among older subjects and both have failed to find any (69,70) (Table 2). In a cohort of women (641 participants aged 70-79 from the Women's Health and Aging Studies), Wang et al reported an inverse association between thyroid antibodies and frailty, irrespective of thyroid functional status.…”

“…On this evidence, frail individuals who suffer from weight loss and reduced lean mass, appear to be particularly at risk of overtreatment among older people, and thyroid hormone excess may have negative consequences beyond the well-known adverse effects, contributing to the pathogenesis of frailty itself. Indeed, besides lowering TSH, thyroid replacement therapy excess affects serum FT4 levels, which are independent predictors of frailty (68,70,77,78). Several studies have demonstrated that patients under l-T4 therapy have higher levels of FT4 than controls, even if within normal values, and serum FT4 concentrations are often at the upper limits of normal range (27,45).…”