Thyroid hormone deficiency-induced cardiac ion channel dysfunction: Molecular mechanisms and arrhythmic implications.

Thyroid hormones are essential regulators of cardiac excitability, contractility, and rhythm. Hypothyroidism induces profound electrophysiological remodeling through both genomic and non-genomic pathways, leading to altered expression and function of key ion channels, including HCN, Kv, and Ca²⁺-handling proteins. These changes result in reduced pacemaker activity, prolonged repolarization, and impaired excitation-contraction coupling, which collectively contribute to bradycardia, QT prolongation, and increased arrhythmogenic risk. Elevated thyroid-stimulating hormone (TSH) levels further exacerbate electrical instability through direct myocardial signaling. Experimental and clinical evidence indicates that many of these abnormalities could be reversible upon thyroid hormone replacement, emphasizing the importance of early diagnosis and multidisciplinary management. Understanding the molecular basis of thyroid-induced electrical remodeling provides insight into arrhythmogenesis and may guide therapeutic strategies to prevent cardiac complications in hypothyroidism.