Subclinical thyroid dysfunction and mortality: an estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies

Objectives: To what extent persons with subclinical hyper- or hypothyroidism are more (or less) likely to die than euthyroid control subjects remains a matter of controversy. Methods: We searched electronic reference databases up to July 31. 2007. Three reviewers independently assessed eligibility. Cohort studies published in full that reported data on the hazard ratio (HR) for mortality from all causes in persons with subclinical thyroid dysfunction versus euthyroid controls were included. Results: Based on seven cohorts including 290 participants with subclinical hyperthyroidism, random-effects models estimated that the pooled HR for all-cause mortality was 1.41. (95% confidence interval (CI). 1.12-1.79: P=0.004). Using the pooled HR and standard life-table methods applied to a US reference population, we estimated that a white US woman, when diagnosed with subclinical hyperthyroidism at age of 70, has an excess mortality of 1.5, 4.0, and 8.7% at 2, 5. and 10 years respectively after diagnosis. Likewise, a white US man has an excess mortality of 2.3, 5.7, and 10.7%. For the nine cohorts including 1580 participants with subclinical hypothyroidism, observed heterogeneity (Q test P=0.006: I-2=63%) disappeared after pooling cohorts in predefined subgroups according to the presence or absence of a comorbid condition. In doing so. the pooled HR for all-cause mortality was 1.03 (95% CI, 0.78-1.35; P=0.83) in cohorts from the community and 1.76 (95% CI, 1.36-2.30; P<0.001) in cohorts of participants with comorbidities (P=0.014 for heterogeneity among study groups). Conclusions: Individuals with subclinical hyperthyroidism demonstrate a 41% increase in relative mortality from all causes versus euthyroid control subjects. Mathematical modeling suggests that absolute excess mortality after diagnosis might depend on age. with an increase beyond the age of 60. especially in aging men. For patients with subclinical hypothyroidism. the relative risk of all-cause mortality is increased only in patients with comorbid conditions.