Multigenerational thyroid hormone resistance due to THRβ mutation

Area of Science:

• Endocrinology
• Cardiology
• Genetics

Background:

• Resistance to thyroid hormone (RTH) is a rare genetic disorder stemming from mutations in thyroid hormone receptor genes (THRα, THRβ).
• While systemic effects are known, cardiac manifestations like cardiomyopathy and heart failure are often overlooked.
• This case highlights the critical need for cardiological awareness in RTH diagnosis and management.

Observation:

• A 50-year-old female with a THRβ gene mutation (c.1357C > A, p.P453T) presented with goiter, hypothyroidism, and progressive cardiac issues.
• She experienced angina, atrial fibrillation, heart failure, and dilated cardiomyopathy (DCM) with ejection fraction <30%, ultimately requiring heart transplantation.
• The mutation was familial, indicating autosomal dominant inheritance.

Findings:

• RTH can be a significant, yet underrecognized, cause of refractory cardiac failure.
• The patient's cardiac condition worsened despite optimal medical therapy, necessitating heart transplantation.
• Management was complex due to thyroidectomy, levothyroxine therapy, and post-transplant immunosuppression.

Implications:

• Cardiologists should suspect RTH in unexplained or treatment-resistant cardiomyopathy, especially with a family history of thyroid disease or arrhythmias.
• Early diagnosis of RTH-related cardiomyopathy is vital for effective management.
• A multidisciplinary approach involving endocrinology and cardiology is essential for optimizing patient outcomes.