OR26-06 Cardiovascular Morbidity And Mortality In Patients With Resistance to THYROID Hormone (RTH): A Linked Record Study

Disclosure: O. Okosieme: None. D. Usman: None. P. Taylor: None. C. Dayan: None. G. Lyons: None. C.M. Moran: None. V.K. Chatterjee: None. A. Rees: None. Introduction: Individuals with Resistance to Thyroid Hormone β (RTH-β) may develop cardiac disease, including cardiomyopathy or arrhythmia. Long-term survival outcomes in this group of patients have not been systematically evaluated. Objectives: We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTH-β in endocrine clinics in Wales. Methods: In a retrospective cohort study using linked datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank, Welsh patients with genetically-proven RTH-β were identified from laboratory records (n=55), matched to population controls by age and sex (n=2750), and linked to outcomes in SAIL. We used Kaplan-Meier and Cox regression models to analyse the association of RTH-β with all-cause mortality, acute myocardial infarction, atrial fibrillation, heart failure, strokes and major adverse cardiovascular events (MACE; a composite of cardiovascular death, acute myocardial infarction, heart failure, and strokes). We also investigated any association between baseline thyroid hormone concentrations and outcomes using restricted cubic splines. Results: Compared to controls, patients had an increased risk of all-cause mortality (Hazard ratio [HR] 2.84, 95% Confidence Interval [95%CI] 1.59-5.08), MACE (HR 3.49, 95%CI 2.04-5.99), atrial fibrillation (HR 10.56, 95%CI 4.72-23.63), and heart failure (HR 6.35, 95%CI 2.26-17.86). Positive associations between FT4 concentration at diagnosis and subsequent cardiovascular morbidity or death were observed, with a 7% increased risk of death per pmol/L increase in FT4. The relationship between FT4 and outcomes was non-linear, with increased risk associated with FT4 concentration exceeding 30 pmol/L. When compared to no intervention, treatment with antithyroid drugs, radioiodine/surgical ablation or levothyroxine, alone or in combination, did not effectively control thyroid hormone excess in the long-term. Conclusion: Patients with RTH-β have increased mortality and cardiovascular outcomes that correlates with high, circulating thyroid hormone levels. Ideal future therapies would target both thyroid hormone excess and tissue resistance and could potentially reduce cardiovascular risk in this disorder. Presentation: Saturday, June 17, 2023