FRI496 A Rare Case Of Thyroid Hormone Resistance Beta

Abstract

Abstract Disclosure: H.K. Rai: None. R.M. Pradhan: None. A. Chaudhuri: None. Background: Genetic mutation in the thyroid hormone receptor leads to the reduced affinity of hormone binding; thus, causing thyroid hormone resistance. It is characterized by a wide range of phenotypic variations and subsequent diagnostic and treatment challenges. Here, we present a case of resistance to the thyroid hormone Beta, with a rare genetic abnormality, that was misdiagnosed as hyperthyroidism. Case: A 46-year-old woman diagnosed with hyperthyroidism s/p RAIA resulting in hypothyroidism on levothyroxine therapy (112mcg daily, weight: 55kg), presented with ten pounds of weight gain, constipation, and cold intolerance for the past six months. TFTs were as follows: TSH: 6.493 mcUnits/ml (normal: 0.400-5.00 mcUnits/ml), and free T4: 1.83 ng/dL (normal: 0.80-1.80 ng/dL). The patient was clinically hypothyroid despite having an elevated FT4 and TSH level. She was also on metoprolol succinate 25 mg daily for sinus tachycardia for the past 1 year. Upon inquiring about further details, the patient informed that at the age of 22, she had significant weight loss, palpitations, and anxiety, but also reported dry skin. The patient was seen by multiple endocrinologists and was provided with contradictory diagnoses. She had RAI scan which was significant for increased uptake and subsequently underwent RAIA. The patient was seen by multiple physicians in the past, levothyroxine dose was adjusted on various occasions but her TFTs never normalized. Post-ablation, she continued to require a higher than the weight-based dose of levothyroxine. Upon review of family history, the patient reported that her father, sister, and daughter had a similar pattern of TFTs with elevated FT4 and TSH values. All of them had palpitations and anxiety that were not severe enough to seek medical care. Family history was also significant for ADHD and hyperlipidemia present in the daughter and father. All affected family members have short stature. The levothyroxine dose was slowly titrated based on the clinical presentation. She was euthyroid with 150 mcg daily of levothyroxine with TSH of 4.869 mcUnits/ml and free T4: 1.85 ng/dl. Given her presentation and suspicion of thyroid hormone resistance, we decided to proceed with genetic testing. The result was positive for the THRB (Resistance to thyroid hormone beta) variant c.904A>G.p.(IIe302Val), which is classified as a variant of uncertain significance, as there is currently insufficient evidence to support its disease-causing role. However, there is a strong association between the gene and the patient's phenotype. Conclusion: The distinctive feature of RTH beta is high levels of free T4 while TSH concentration is normal or elevated, with a combination of hypothyroid and hyperthyroid symptoms. Such patients are often misdiagnosed. We herein describe a novel pathogenic RTH beta gene variant causing thyroid hormone resistance that needs to be further explored. Presentation: Friday, June 16, 2023