SAT-409 Evaluating the Role of Liothyronine and Levothyroxine Combination Therapy in Persistent Hypothyroidism Symptoms: A Case Series

Abstract Disclosure: R.N. Tacata: None. K. Peterman: None. N. Cerezo: None. I. Casimiro: None. Background: Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism, relying on peripheral conversion of T4 to the active T3 hormone. However, a subset of patients with hypothyroidism on levothyroxine (LT4) monotherapy experience dissatisfaction, fatigue, and depression despite a normal thyroid stimulating hormone (TSH). Here we explore the possibility that some patients may require treatment with synthetic liothyronine (LT3) in addition to LT4 in order to achieve both biochemical and clinical euthyroidism. Objectives: This study aims to explore the use of LT3 and LT4 combination therapy in patients with hypothyroidism. Methods: Three patients with hypothyroidism were evaluated for ongoing symptoms such as fatigue, bradycardia, constipation and/or weight gain despite normal TSH on LT4 monotherapy. Each had TSH and Free T4 within normal limits but T3 levels were below normal. Combination therapy was initiated by reducing LT4 dosage and adding LT3, with clinical and biochemical follow-up. Results: Case 1: A 67-year-old female with idiopathic bradycardia and persistent hypothyroid symptoms demonstrated improved TT3 from 67 ng/dL to 107 ng/dL with resolution of fatigue and improvement in episodes of bradycardia, following LT3 initiation. Case 2: A 58-year-old female with post-ablative hypothyroidism due to Graves’ disease showed improved TT3 from 72 ng/dL to 86 ng/dL and improved fatigue and constipation after LT3 addition. Case 3: A 40-year-old male status post-thyroidectomy for papillary thyroid carcinoma experienced an increase in TT3 from 78 ng/dL to 96 ng/dL and alleviation of fatigue after combination therapy. Conclusion: This case series highlights the potential benefit of LT3 and LT4 combination therapy for patients with hypothyroidism and persistent symptoms despite normalized TSH level. Impaired peripheral T3 conversion may play a role in these cases and monitoring TT3 alongside TSH and FT4 can guide therapy adjustments. Further research is needed to better understand the role of managing the role of combination therapy in patients with refractory hypothyroid symptoms. Presentation: Saturday, July 12, 2025