Cardiac complications of thyroid hormone resistance syndromes

Area of Science:

• Endocrinology
• Cardiology
• Molecular Biology

Background:

• Thyroid hormones regulate cardiac function via thyroid hormone receptors (TRs).
• Mutations in TRβ cause thyroid hormone resistance (TRH), affecting cardiac phenotype.
• TRα mutations also influence cardiac function, distinct from TRβ.

Purpose of the Study:

• To investigate the cardiac manifestations in patients with TRH due to TRβ mutations.
• To characterize the cardiac phenotype associated with TRα mutations.
• To explore potential genotype-phenotype correlations and treatment effects.

Main Methods:

• Review of patient cohorts with documented TRβ and TRα mutations.
• Clinical assessment of cardiac symptoms, rhythm, and function (systolic and diastolic).
• Comparison of cardiac parameters between mutated patients and euthyroid/hyperthyroid subjects.

Main Results:

• TRβ mutations are linked to tachycardia, palpitations, arrhythmias (up to 20% atrial flutter/fibrillation), and impaired systolic/diastolic function.
• No heart failure cases reported in TRβ patients; no genotype-phenotype correlation found.
• TRα mutations are associated with bradycardia and hypothyroid-like cardiac function; levothyroxine shows partial improvement.

Conclusions:

• Thyroid hormone receptor mutations significantly alter cardiac function and rhythm.
• TRβ mutations lead to a distinct cardiac phenotype, while TRα mutations mimic hypothyroidism.
• Current treatments offer limited improvement for these genetically driven cardiac conditions.