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

Abstract

Objective: Thyroid dysfunction predicts poorer health outcomes, but the relationship between thyroid hormone levels within the reference range and mortality in older adults remains unclear. In this study, we examined the associations between the concentrations of free thyroxine (FT 4 ) and TSH and allcause mortality in older men without thyroid disease. Subjects and methods: We performed a longitudinal study in community-dwelling men aged 70-89 years. Men with thyroid disease or taking thyroid-related medications were excluded. Baseline FT 4 and TSH levels were assayed. Incident deaths were ascertained using data linkage. Results: There were 3885 men without thyroid disease followed for (meanGS.D.) 6.4G1.5 years, during which time 837 had died (21.5%). Men who had died had higher baseline FT 4 levels (16.2G2.3 vs 15.8G2.1 pmol/l, P!0.001), but comparable TSH levels (2.4G1.5 vs 2.3G1.5 mIU/l, PZ0.250). After accounting for age, smoking, physical factors and medical comorbidities, higher circulating FT 4 levels predicted all-cause mortality (quartile Q4 vs quartiles Q1-Q3: FT 4 levels R17.32 vs !17.32 pmol/l: adjusted hazard ratio (HR)Z1.19, 95% CIZ1.02-1.39, PZ0.025). TSH levels did not predict mortality. After excluding men with subclinical hyperthyroidism or hypothyroidism, there were 3442 men and 737 who had died (21.4%). In these men, higher FT 4 levels remained independently associated with all-cause mortality (quartile Q4 vs quartiles Q1-Q3: adjusted HRZ1.19, 95% CIZ1.02-1.41, PZ0.032). Conclusions: Higher FT 4 levels are associated with all-cause mortality in euthyroid older men, independently of conventional risk factors and medical comorbidities. Additional research is needed to determine whether or not this relationship is causal and to clarify the utility of thyroid function testing to stratify mortality risk in ageing men.

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

“…It has been recently reported that all-cause mortality is associated with higher FT4 but not TSH variations in euthyroid elderly men. 30 The current study differs from that study on several points. First, only men were examined in that study, so it is difficult to draw any conclusions for the general population.…”

“…It has been recently reported that in euthyroid elderly men all-cause mortality is associated with higher FT4 but not TSH variations (30). Our study differs from the study reported above in several points.…”

Reply on the Letter by Stott et al. ‘The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines Do More Harm than Good'

“…The guidelines specifically recommend (recommendation 15) that the oldest old subjects (>80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. This procedure is supported by a recent study showing that older patients are at particular risk for overtreatment, as their upper limit of normal for the level of TSH is slightly higher than that in younger patients [7]. Among 3,900 community-dwelling apparently euthyroid Caucasian Australian men over 70 years of age, those whose free thyroxine was normal but in the highest quartile were 20% more likely to have died over 6 years of follow-up.…”

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

“…In another study by Murphy et al, evaluating 1278 healthy euthyroid postmenopausal women, higher FT4 within the normal range was associated with lower hip bone mineral density, increased bone loss and non-vertebral fracture risk (75). 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).…”