Management of Cardiovascular Morbidity Associated with Resistance to Thyroid Hormone Beta

Background: Resistance to thyroid hormone beta (RTHβ) is a rare genetic disorder characterized by impaired thyroid hormone receptor β (TRβ) function, leading to resistance to thyroid hormones (THs) in TRβ-dependent tissues. Although traditionally considered a benign condition, emerging evidence highlights increased cardiovascular morbidity. Summary: In RTHβ, impaired TRβ2 function, responsible for central regulation of TH, leads to increased TH levels. The heart is TRα1-dependent, being chronically overexposed to TH, often resulting in sinus tachycardia and increased arrhythmic risk. Other cardiac changes include enlarged left chambers, increased cardiac output and valvular abnormalities, predisposing to heart failure and/or increased cardiovascular and all-cause mortality. Free thyroxine, age at diagnosis, and comorbidity burden positively correlate with risk of major adverse cardiovascular events. RTHβ is also associated to dyslipidemia and hepatic steatosis, further compounding cardiovascular risk. β-blockers are considered first-line therapy for tachycardia and atrial fibrillation, although they do not correct the underlying imbalance. The TRβ-selective analogue 3,5,3′-triiodothyroacetic acid (TRIAC) represents a theoretically promising therapeutic option. Key Messages: Cardiovascular complications in RTHβ are often underestimated. Management should include routine cardiac monitoring, aggressive control of cardiovascular risk factors, and consideration of emerging therapies such as TRIAC, though more trials are needed to confirm their safety and efficacy.