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Resistance to thyroid hormone in a patient with coexisting Graves' disease.

BACKGROUND
Resistance to thyroid hormone (RTH) is a rare disorder in which an abnormality in the binding domain of the thyroid hormone receptor results in end-organ insensitivity to the actions of thyroid hormones. This disorder is sometimes misdiagnosed as Graves' disease due to the presence of a goiter with high Iodine-123 thyroid uptake and high levels of total and free thyroid hormones. Additionally, some patients with RTH may experience palpitations or tachycardia. There is a previous report of a patient with pituitary RTH and concurrent Graves' disease.


SUMMARY
We describe a patient who was found to have a goiter with signs and symptoms of hyperthyroidism by his primary care physician. Work-up revealed a low thyroid stimulating hormone (TSH), high thyroid-stimulating immunoglobulins, high Iodine-123 thyroid uptake, as well as increased homogenous activity in both thyroid glands on nuclear scan and a suppressed TSH. Diagnosis of Graves' disease was made, and the patient underwent radioactive ablation of the thyroid gland. The patient subsequently developed hypothyroidism and required a much higher dose of levothyroxine than his weight-based estimate of a full replacement dose to maintain euthyroidism. On 325 micog of daily levothyroxine the patient was clinically euthyroid and had a normal TSH although his levels of T3 and T4 were high. Work-up revealed a mutation in the thyroid hormone beta-receptor gene, consistent with diagnosis of RTH.


CONCLUSIONS
RTH is often misdiagnosed as Graves' disease. However, these disorders can coexist, and the concurrent presence of both disorders in a patient can present diagnostic challenges. A previous report of a patient with Graves' disease associated with RTH was published before gene sequencing could be used to confirm diagnosis of RTH. We present a patient with Graves' disease and concurrent RTH that was confirmed by gene sequencing, showing a mutation in the thyroid hormone receptor beta gene.