End-stage renal disease (ESRD) patients have an increased incidence of hypothyroidism, and those with serum thyroid stimulating hormone (TSH) levels above the reference range have excess mortality, increased cardiovascular disease, impaired health-related quality of life, and altered body composition. We report a patient with ESRD on chronic hemodialysis and Hashimotos disease, who is on chronic levothyroxine therapy. Despite a high levothyroxine dose of 2.12 mcg/kg and regular adherence, the patient had elevated TSH levels and a pattern of erratic TSH levels. The patient was on the phosphate binder, sevelamer, which has been associated with reduced levothyroxine absorption. The patient was switched to a liquid levothyroxine preparation at the same dose, and after two months, free thyroxine levels normalized and TSH levels improved. The implications of hypothyroidism in patients with ESRD are discussed, along with approaches to managing erratic serum TSH levels and the use of liquid levothyroxine preparations to improve serum TSH levels in patients taking medications that reduce absorption.