Abstract
Disclosure: S.V. Ribeiro: None. T. Moreno: None. A. Varela: None. P. Freitas: None. D.M. Carvalho: None. Resistance to thyroid hormone (RTH) is a rare clinical syndrome defined by hyposensitivity to thyroid hormone (TH) and characterized by elevated TH levels in the absence of TSH suppression. In most subjects with RTH, treatment is not required as tissue resistance is adequately compensated for by an increase in the endogenous supply of TH. This is not the case in patients with limited thyroidal reserve. Here we describe the clinical features of two unrelated patients with RTH and coexisting thyroid disease. Patient 1 was an 18-year-old female medical student referred to our consultation from Pediatrics. She had been diagnosed with autoimmune thyroiditis at age of 7 following the development of an obvious goiter. By then her thyroid-function tests (TFT) showed elevated TSH (8.75 µIU/mL, NR 0.41-3.67) and a normal free T4 (1.3 ng/dL, NR 0.82-1.76). She tested positive for the presence of antibodies to thyroperoxidase and thyroglobulin. The cytological findings on aspiration biopsy were consistent with Hashimoto’s thyroiditis. Throughout the years, despite levothyroxine supplementation she displayed systematically elevated TSH and normal FT4. The results of a thyrotropin stimulation test were normal. The suspicious of erratic compliance to therapy was raised.Follow-up at our outpatient clinic confirmed requirement for unusually high replacement doses of levothyroxine in order to maintain TSH within normal limits at expense of elevated FT4 and FT3 levels, suggesting the possibility of RTH. She was found with a THRβ c.1292T>C p.(Iso431Thr) heterozygous mutation. She remains clinically euthyroid under supplementation. Patient 2 was an asymptomatic 54-year-old female who consulted us for further evaluation of a thyroid nodule. Thyroid-FT showed an elevated FT3, at 3.86 μg/dL (NR, 1.75 to 3.71), an elevated FT4 at 1.86 ng/dL (NR 0.70 to 1.48), and a normal TSH level at 1.55 µIU/mL (NR, 0.40 to 4.50). A diffuse goiter was revealed by scintigraphy and the ultrasound showed no relevant findings. A diagnosis of RTH was genetically confirmed (THRβ c.1707C>G p.(P453A)). After a 6-year follow-up, she was diagnosed with supraventricular tachyarrhythmia for which she was started on amiodarone. Shortly after, her TFT revealed elevated TSH that normalized a few months after amiodarone withdrawal. Three years later, she was admitted to the intensive care unit due to cardiogenic shock attributed to tachycardia-induced cardiomyopathy and restarted on amiodarone. Her subsequent TFT showed elevated TSH (42.07 µIU/mL), with decreasing levels of TH (FT3 2.02 μg/dL, FT4 1.06 ng/dL). A diagnosis of amiodarone-induced hypothyroidism was made and levothyroxine supplementation was initiated and adjusted considering the patient’s symptoms. These cases show that the coexistence of RTH with other thyroidal disease can make diagnosis and management challenging and requires awareness and long-term follow-up. Presentation Date: Saturday, June 17, 2023