A critical review and meta-analysis of the association between overt hyperthyroidism and mortality

Background: Overt hyperthyroidism has been associated with cardiac arrhythmias, hypercoagulopathy, stroke, and pulmonary embolism, all of which may increase mortality. Some, but not all, studies show an increased mortality in patients with hyperthyroidism. This inconsistency may be due to differences in study design, characteristics of participants, or confounders. In order to test whether hyperthyroidism influences mortality, we performed a critical review and statistical meta-analysis. Methods: Based on an electronic PubMed search, using the Medical Subject Heading words such as hyperthyroidism, thyrotoxicosis, and mortality or survival, case-control and cohort studies were selected and reviewed. Using meta-analysis, an overall relative risk (RR) of mortality was calculated. Results: Eight studies fulfilled the inclusion criteria, six of which showed an increased all-cause mortality; seven studies, including 31 138 patients and 4 00 000 person years at risk, allowed calculation of mortality in a meta-analysis. Based on this, the RR of overall mortality was 1.21 (95% confidence interval: 1.05-1.38). Analyses including studies considering setting, treatment, and control for co-morbidity did not significantly alter this finding. As the measured heterogeneity (I 2) ranges from 89.1 to 98.3%, which is much higher than the 50% generally viewed on as a threshold, the statistical heterogeneity is very pronounced in the included studies. Conclusion: In patients diagnosed with hyperthyroidism, mortality is increased by similar to 20%. Future studies need to address the cause of hyperthyroidism, impact of type of therapy, time dependency, as well as the potential influence of confounding or genetic susceptibility before the question of causality can be answered.