8747 A Rare Receptor Resistance with Paradoxical Outcomes!

Abstract Disclosure: I. Patoli: None. S. Batool: None. A.S. Gill: None. A. Makdissi: None. Introduction: Resistance to thyroid hormone receptor is an uncommon cause of abnormal TFTs. (1) We present an interesting case of THRB resistance with cardiac arrhythmia (CA). Clinical Case: 46-year-old man with history of atrial fibrillation (Afib) was referred to endocrinology for evaluation of abnormal TFTs and thyroid nodule. He had a recent hospital admission for Afib with rapid ventricular response; 3 years ago, he was treated with amiodarone for 2 months. TFTs revealed normal TSH of 1.375, elevated FT4 of 2.76 (normal ranges 0.55-4.78 and 0.89-1.76, respectively). Neck CT scan showed large peripherally enhancing centrally necrotic mass with calcification encompassing nearly the entirety of left thyroid lobe measuring 2.2 x 3.6 x 4.6 cm. A 0.8 cm hypodensity within right thyroid lobe also visualized. Thyroid ultrasound showed nodules bilaterally with the largest one in the lower pole of left lobe. FNA biopsy showed Bethesda category- II benign, benign appearing follicular cells and abundant colloid. Repeat labs showed similar results with persistently elevated free T4 (2.56) with equilibrium dialysis, normal alpha subunit, normal TSH (2.14) with human anti-mouse antibody (HAMA) antibody was negative. Alpha subunit:TSH ratio was <1. He remained clinically euthyroid over the course of 1.5 year but repeat labs at that time indicated that TSH had increased to 17 with elevated free T4 (2.6) . MRI brain ruled out TSH secreting adenoma. He reported thyroid abnormalities in son and brother but was unable to provide details. He was referred for genetic screening which showed THRB with pathogenic variant: c.9628> G (p.Y321C). Conclusion: THRB resistance is an uncommonly diagnosed modality in endocrinology. The genes encoding thyroid hormone receptors are THRα gene and THRβ gene (2). Patients with inherited THRB pathogenic variants present with resistance to thyroid hormone and often enlarged thyroid gland. Interestingly, despite having receptor resistance, patients may manifest with CA. This is hypothesized to be due to elevated T4 and T3 concentration in the heart which primarily has higher expression of THRA (3). The diagnosis of thyroid hormone resistance is important to avoid treating asymptomatic patients where treatment is not warranted. References: 1. Larsen CC, et al. Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease. Thyroid. 2013 Dec;23(12):1638-43. 2. Ortiga-Carvalho TM, et al. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol. 2014;10(10):582-591. 3. Wikström L, et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. EMBO J. 1998 Jan 15;17(2):455-61. Presentation: 6/2/2024