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

Eur J Endocrinol. 2013 Sep 12;169(4):401-8. doi: 10.1530/EJE-13-0306. Print 2013 Oct.


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 (FT4) and TSH and all-cause 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 FT4 and TSH levels were assayed. Incident deaths were ascertained using data linkage.

Results: There were 3885 men without thyroid disease followed for (means.d.) 6.41.5 years, during which time 837 had died (21.5%). men who had died had higher baseline ft4 levels (16.22.3 vs 15.82.1 pmol/l, p0.001), but comparable tsh levels (2.41.5 vs 2.31.5 miu/l, P=0.250). After accounting for age, smoking, physical factors and medical comorbidities, higher circulating ft4 levels predicted all-cause mortality (quartile Q4 vs quartiles Q1Q3: FT4 levels ≥ 17.32 vs <17.32 pmol/l: adjusted hazard ratio (HR)=1.19, 95% CI=1.02-1.39, P=0.025). 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 FT4 levels remained independently associated with all-cause mortality (quartile Q4 vs quartiles Q1-Q3: adjusted HR=1.19, 95% CI=1.02-1.41, P=0.032).

Conclusions: Higher FT4 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Asymptomatic Diseases / mortality
  • Comorbidity
  • Humans
  • Hyperthyroidism / blood
  • Hyperthyroidism / mortality*
  • Hypothyroidism / blood
  • Hypothyroidism / mortality*
  • Incidence
  • Longitudinal Studies
  • Male
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Reference Values
  • Risk Factors
  • Thyroid Function Tests / standards
  • Thyroid Gland / physiology*
  • Thyrotropin / blood
  • Thyroxine / blood*


  • Thyrotropin
  • Thyroxine