Endocrine Abstracts

Resistance to Thyroid Hormone-β (RTHβ) is a rare disorder characterised by hormone resistance in the pituitary-thyroid axis which results in elevated, circulating thyroid hormones. Although some patients display features of hyperthyroidism, the natural history of RTHβ with respect to cardiovascular disease or death is unknown. In this presentation, I will review our recent data which used a linked health record approach in Wales to demonstrate reduced survival and increased cardiovascular risk in patients with RTHβ. Compared to unaffected controls, RTHβ patients exhibited a three-fold increase in all-cause mortality or major cardiovascular events, particularly excess risks of atrial fibrillation and heart failure. The median age of first occurrence of any adverse event was 11 years earlier in patients compared to controls. Positive associations were observed between thyroid hormone levels at baseline and cardiovascular morbidity or death, suggesting that lifelong exposure to elevated thyroid hormones mediates the increased morbidity and mortality. Conventional treatments for hyperthyroidism (antithyroid drugs, radioiodine ablation or thyroidectomy) did not control thyroid hormone levels effectively. Our findings suggest that careful management of cardiovascular risk in RTHb patients is warranted and that clinical trials of therapies that target hormone resistant pathways are needed.