MON-465 Novel Thyroid Hormone β Mutation L266s Causes Atrial Fibrillation & Cerebral Infarction

Abstract Background: Resistance against thyroid hormone β (RTHβ) is characterized by reduced tissue sensitivity to thyroid hormone. Patients with RTHβ resistance typically demonstrate increases in FT3 and FT4 accompanied by inappropriately elevated TSH. Mutations in the TRβ gene are the most common genetic disorder in thyroid hormone resistance and result in impaired thyroid receptor functions due to a dominant negative effect. Here, we describe a case with a novel TRβ mutation, presenting atrial fibrillation and cerebral infarction. Clinical case: A 55-year-old man presented chronic atrial fibrillation and tachycardia as the onset of cerebral infarction. Because blood tests revealed 5.6 pg/ml FT3 (reference range: 2.36–4.06), 3.39 ng/ml FT4 (0.71–1.5), 0.98 TSH μIU/ml (0.541–4.261), and negative TRAb, suggesting inappropriate secretion of TSH (SITSH). He was referred to our department for further investigation. All three test kits, including LUMIPULSE, ECLusys, and TOSOH, showed an unsuppressed TSH value despite hyperthyroxinemia, demonstrating genuine SITSH. His family history was unclear, but his father had died of heart disease. A pituitary MRI suggested microadenoma, but TSH-secreting pituitary adenoma was excluded because of a negative α subunit and responsiveness to a TRH stimulation test. The TRβ gene was analyzed with informed consent from the patient, and a novel mutation replacing the 266th amino acid serine (TCG) with leucine (TTG) in the 8th exon was found, confirming the diagnosis of RTHβ. Tachycardia and atrial fibrillation were considered to be caused by thyrotoxicosis in heart, which dominantly expresses TRα rather than TRβ. Therefore, β-blockers and anticoagulants, were continued. Conclusion: This is the first report of a case of RTHβ with the TRβ L266S mutation. This novel mutation is located in the thyroid hormone-binding area of the TRβ gene, suggesting that reduced hormone binding may cause thyroid hormone resistance.