Thyroid Function and Mortality Risk in Multimorbidity: Insights from Two Cohorts
Overview
This study investigated the relationship between thyroid hormone levels and all-cause mortality in individuals with varying degrees of multimorbidity using data from the PREVEND and Rotterdam population-based cohorts. Higher free T4 levels were associated with increased mortality risk, particularly in those with multimorbidity, while higher free T3 levels correlated with lower mortality risk in individuals with one or multiple diseases.
Background
Multimorbidity, defined as the coexistence of two or more chronic diseases, is prevalent in aging populations and is linked to higher mortality and healthcare burden. Thyroid dysfunction is common in these populations and influences cardiovascular and other noncommunicable disease risks. Nonthyroidal illness syndrome, characterized by low free T3 without elevated TSH, often occurs in severe illness and may be related to multimorbidity. Understanding how thyroid function impacts mortality in multimorbid individuals is clinically important but not well established.
Data Highlights
Cohort
Participants (n)
Mean Age (years)
HR per 1-unit increase in free T4 Z-score (No disease)
HR per 1-unit increase in free T4 Z-score (1 disease)
HR per 1-unit increase in free T4 Z-score (Multimorbidity)
HR per 1-unit increase in free T3 Z-score (1 disease)
HR per 1-unit increase in free T3 Z-score (Multimorbidity)
Rotterdam Study
9080
64.9
1.07 (1.03-1.12)
1.09 (1.04-1.15)
1.21 (1.11-1.31)
0.82 (0.70-0.97)
0.80 (0.61-1.05)
PREVEND
5537
53.0
Trend similar but nonsignificant
Trend similar but nonsignificant
Trend similar but nonsignificant
Not specified
Not specified
Key Findings
Higher free T4 concentrations were significantly associated with increased all-cause mortality risk in the Rotterdam Study, especially among individuals with multimorbidity (HR 1.21 per 1-unit Z-score increase).
A similar but statistically nonsignificant trend for free T4 and mortality was observed in the PREVEND cohort.
Higher free T3 concentrations were associated with lower mortality risk in individuals with one disease (HR 0.82) and showed a trend toward lower mortality in those with multimorbidity (HR 0.80) in the Rotterdam Study.
The association between thyroid function and mortality varied according to disease burden, with stronger effects seen in multimorbid individuals.
Participants on thyroid medications or with diagnosed thyroid disease were excluded to avoid confounding.
Clinical Implications
Clinicians should be aware that elevated free T4 levels may indicate increased mortality risk in patients with multimorbidity, while higher free T3 levels might be protective. Monitoring thyroid hormone levels could provide prognostic information in multimorbid populations. Further research is needed to determine if these associations apply to patients receiving thyroid hormone replacement therapy.
Conclusion
This study demonstrates that thyroid hormone levels, particularly free T4 and free T3, are differentially associated with mortality risk depending on multimorbidity status in the general population. These findings highlight the importance of considering thyroid function in the clinical management of patients with multiple chronic diseases.
References
Author/Source/2024 -- Thyroid Activity and Overall Mortality in Relation to Multimorbidity: Findings from Two Population-Based Studies
