Endocrine Abstracts

A 42-year-old man with resistance to thyroid hormone (RTH) and a recognised thyroid hormone receptorβ mutation (R383C) mutation, presented with atrial fibrillation (AF) which was resistant to DC cardioversion until initiation of amiodarone therapy.

As expected in RTH, his baseline TFTs were abnormal (FT₄ 34.6 pmol/l, TSH 2.27 mU/l), but rose further (FT₄ 45 pmol/l, TSH 0.93 mU/l) following commencement of amiodarone. However, shortly thereafter, his thyroid hormones (FT₄ >100 pmol/l, FT₃ 22 pmol/l) became very elevated with suppressed TSH (<0.01), positive anti-TSH receptor antibodies (10.4, NR<1) and proptosis, consistent with Graves’ disease. Amiodarone was discontinued and high dose carbimazole (60 mg) restored euthyroidism. However, following discontinuation of titrated thionamide therapy at 6 months, his thyrotoxicosis has recurred and he is now controlled with carbimazole. We are considering definitive treatment.

Due to predominance of normal TRα in myocardium, cardiac sensitivity to elevated thyroid hormones is retained in RTH, manifesting as tachycardia (26%) or atrial fibrillation (6%) (1); known association of the R383C TRβ mutation with greater pituitary than peripheral resistance, may have predisposed to AF in this case. As in conventional thyrotoxicosis, AF in RTH is resistant to cardioversion and controlling heart rate with β blockade is usually advised. Although effective, amiodarone therapy can result in thyrotoxicosis (AIT), which can be especially challenging to manage in the context of RTH. Surgical or radioiodine ablation of the thyroid may be required, but the appropriate dose of subsequent hormone replacement is difficult to determine. Thyroxine replacement in conventional dosage is associated with chronically elevated TSH levels, with attendant risk of pituitary thyrotroph hyperplasia or even adenoma formation (2); conversely, supraphysiological T₄ treatment risks cardiac hyperthyroidism and recurrence of AF.

References

1. Kahaly G. Cardiac involvement in thyroid hormone resistance JCEM 2002 87 (1) 204–212.

2. Gurnell M. Reversible pituitary enlargement in the syndrome of resistance to thyroid hormone Thyroid 1998 8 679–682.