Thyroid Function and All-cause Mortality in the Context of Multimorbidity: Results From 2 Population-based Studies

Thyroid dysfunction is common in aging populations and associated with increased noncommunicable disease risk. Complex disease interactions in multimorbidity may influence this association. We aimed to examine the association between thyroid function and all-cause mortality in the context of multimorbidity.

We included participants with thyroid function measurements and recorded disease status from the PREVEND and the Rotterdam studies and categorized them into 3 groups (no disease, 1 disease, and multimorbidity). We used Cox proportional hazards models for the associations between thyroid function and all-cause mortality. Hazard ratios (HRs) were expressed per 1-unit increment in thyroid function Z-scores.

A total of 5537 participants (mean age, 53.0 years) from PREVEND and 9080 participants (mean age, 64.9 years) from the Rotterdam Study were included. Higher free T4 concentrations were associated with a higher all-cause mortality risk in the Rotterdam Study, with HRs per 1-unit increase in a Z-score of 1.07 (1.03-1.12), 1.09 (1.04-1.15), 1.21 (1.11-1.31) for individuals with no disease, 1 disease, and multimorbidity, respectively (P for trend <.001), whereas a similar but nonsignificant trend was observed in PREVEND. We show a lower mortality risk for higher free T3 concentrations among individuals with 1 disease (HR per 1-unit increase in Z-score: 0.82, 0.70-0.97) and multimorbidity (HR, 0.80; 0.61-1.05) (P for trend = .002).

We show an association between higher free T4 and mortality for individuals with multimorbidity, whereas lower free T3 was associated with poor survival in individuals with multimorbidity. Our results extend findings from patient populations to people with multimorbidity from the general population. Future research is needed to investigate whether these findings extend to levothyroxine users.