7009 Resistance to Thyroid Hormone

Disclosure: S. Gill: None. L.F. Chavez: None. Resistance to thyroid hormone is a unique phenomenon presenting with a variety of clinical findings due to biochemical elevations in thyroid hormones. We describe a case of a 52 year old male diagnosed with hypertension at age 25 followed by atrial flutter resulting in tachycardia induced cardiomyopathy who presented to the emergency department for lightheadedness and palpitations. He was found to be in atrial flutter and converted to normal sinus rhythm after receiving diltiazem. Labs showed a T4 of 17.4 with a TSH of 2.48. On examination, he was back to baseline and denied heat intolerance, changes in bowel habits, weight loss, hair loss, sweating, recent falls or fragility fractures, and in fact felt cold. Physical exam was remarkable for goiter. Patient was previously referred to endocrinology given an elevated FT4 and total T3 with a non-suppressed TSH level concerning for a TSH producing adenoma. He underwent extensive hormonal workup that revealed normal pituitary functioning apart from elevated FT4, FT3, and FT4 by dialysis. MRI of the brain was performed on two occasions, last done a few months prior to hospitalization which showed no focal lesions in the sella or parasellar regions. Given normal TSH and elevated FT4 levels in the setting of negative imaging, patient thought to likely have resistance to thyroid hormone (RTH). RTH is a rare inherited condition seen in as few as 1 in 40, 000 live births. It stems from an inability of target cells to respond appropriately to thyroid hormones due to dysfunction of thyroid hormone receptors (TRs). The most common variant of RTH is due to a mutation in the THRB gene encoding thyroid hormone receptor beta (RTH beta) located on chromosome 3 followed by defects in the THRA gene encoding thyroid hormone receptor alpha (RTH alpha) located on chromosome 17. Others may not have an identifiable genetic defect and are thought to be due to alterations in TR cofactors. Elevations of all three serum iodothyronines with non-suppressed TSH is seen with RTH beta while borderline high T3 and normal or slightly elevated TSH is seen in RTH alpha. Inadequate response to thyroid hormones can lead to feedback mechanisms attempting to resolve this relative deficiency by promoting synthesis of higher than normal thyroid hormone levels. Treatment is usually not required due to this adaptive mechanism but on occasion levothyroxine is supplemented to normalize the TSH in patients with limited thyroid reserve. Despite elevated circulating thyroid hormones, individuals can be clinically euthyroid or experience symptoms of thyroid hormone excess or deficiency. Conditions mimicking RTH including TSH producing adenomas should be ruled out which present with overt hyperthyroidism as opposed to the more subtle symptoms that can be seen with RTH. Overall, clinicians should be aware of RTH to prevent misdiagnosis and pursue treatment modalities that may otherwise not have been needed. Presentation: 6/1/2024