Review: The association of thyroid dysfunction with all-cause and circulatory mortality: is there a causal relationship?

Context: Currently there is ongoing debate on whether subclinical and overt thyroid dysfunction may exert deleterious effects on the cardiovascular system with the consequence of increased mortality in affected individuals. We systematically review studies on the relation of thyroid dysfunction with all-cause and circulatory mortality questioning whether thyroid dysfunction is a causal factor for mortality.

Methods: Two investigators independently searched the MEDLINE database. All case-control and cohort studies published in peer-reviewed journals were selected. Studies on nonthyroidal illness or low-T3 syndrome and reports from highly selected populations were not considered. Risk estimates from studies with appropriate adjustment for confounders were metaanalyzed.

Results: Four among eight studies performed to investigate the association between hyperthyroidism and mortality revealed an increased risk of either all-cause or circulatory mortality. Only the minority of studies, however, adjusted analyses for relevant confounders besides age, sex, and race. Studies after radioiodine therapy were generally biased by indication. Findings from 11 studies that investigated the relation between hypothyroidism and mortality were highly discrepant and partly even mutually exclusive. Some of these discrepancies are explained by confounding and selection.

Conclusions: The currently available evidence for a causal relation of both hyperthyroidism and hypothyroidism with mortality is weak and should particularly not be used to decide whether patients with subclinical thyroid conditions should be treated. Very old individuals might represent an exception from this rule and may benefit from mildly reduced thyroid function, but this has to be substantiated by further research.