Increased risk of multisystem comorbidities and disease trajectories following hyperthyroidism: evidence from the 0.5 million UK Biobank population.

Background and aims: Hyperthyroidism is a clinical syndrome caused by the excessive production of thyroid hormones, which can have a broad impact on overall health. We systematically investigated the subsequent multisystem comorbidities associated with hyperthyroidism and the progression of these conditions. Methods: After a 1:4 propensity score matching, a total of 5,832 hyperthyroidism patients and 22,579 controls from the UK Biobank were included in this study. Phenome-wide association study was conducted to explore the associations between hyperthyroidism and a broad range of subsequent diseases, supplemented by landmark analysis to depict the time-varying effects. Disease trajectory analysis was used to explore the sequential pattern of comorbidity progression of hyperthyroidism. Results: Patients with prior diagnosed hyperthyroidism were observed to have an elevated risk of developing 110 subsequent diseases across multiple systems and all-cause mortality and four causes of death, with particularly marked short-term adverse effects. Disease trajectory analysis demonstrated that the three disease clusters most affected by hyperthyroidism were cardiovascular disease cluster, gastrointestinal inflammatory disease cluster and diabetes-mediated disease cluster. Conclusion: Hyperthyroidism is associated with an elevated risk of subsequent multisystem diseases and mortality. Disease trajectory analysis has elucidated critical sequential patterns of disease progression, offering valuable insights for the management of comorbidities in patients with hyperthyroidism.