The Thyroid Epidemiology, Audit, and Research Study (TEARS): Morbidity in Patients with Endogenous Subclinical Hyperthyroidism

Objective: Our objective was to investigate the long-term outcomes for patients with endogenous subclinical hyperthyroidism (SH). Design: Population record-linkage technology was used retrospectively to identify patients with SH and hospital admissions from January 1, 1993, to December 31, 2009. Patients: All Tayside residents over 18 yr old with at least two serum TSH measurements below the reference range for at least 4 months apart and normal free T-4/total T-4 and normal total T-3 concentrations at baseline were included as potential cases. Using a unique patient identifier, data linkage enabled a cohort of SH cases to be identified from biochemistry, prescription, admission, and radioactive iodine treatment records matched to five comparators from the general population. Outcome Measures: The association between endogenous SH and cardiovascular disease, fracture, dysrhythmia, dementia, and cancer was assessed. Results: Compared with the reference population, SH was associated with an increased risk of nonfatal cardiovascular morbidity, osteoporotic fracture, dysrhythmia, and dementia, with adjusted hazard ratios (HR) of 1.39 (1.22-1.58), 1.25 (1.04-1.50), 1.65 (1.26-2.17), and 1.64 (1.20-2.25), respectively. When SH patients who developed overt hyperthyroidism during follow-up were excluded, SH patients were associated with an increased risk of cardiovascular morbidity [HR = 1.36 (1.19-1.57)], dysrhythmia [HR = 1.39 (1.02-1.90)], and dementia [HR = 1.79 (1.28-2.51)] but not fracture and cancer. Conclusion: Patients with endogenous SH have an increased risk of cardiovascular disease and dysrhythmia. There is an association with fracture and dementia that is not related to TSH concentration and therefore is less likely to be causally related. No association was found between SH and cancer. (J Clin Endocrinol Metab 96: 1344-1351, 2011)