Levothyroxine is a synthetically produced form of thyroxine, a major endogenous hormone secreted by the thyroid gland. Also known as L-thyroxine or the brand name product Synthroid, levothyroxine is used primarily to treat hypothyroidism, a condition where the thyroid gland is no longer able to produce sufficient quantities of the thyroid hormones T (tetraiodothyronine or thyroxine) and T (triiodothyronine or Liothyronine), resulting in diminished down-stream effects of these hormones. Without sufficient quantities of circulating thyroid hormones, symptoms of hypothyroidism begin to develop such as fatigue, increased heart rate, depression, dry skin and hair, muscle cramps, constipation, weight gain, memory impairment, and poor tolerance to cold temperatures. In response to Thyroid Stimulating Hormone (TSH) release by the pituitary gland, a normally functioning thyroid gland will produce and secrete T, which is then converted through deiodination (by type I or type II 5′-deiodinases) into its active metabolite T. While T is the major product secreted by the thyroid gland, T exerts the majority of the physiological effects of the thyroid hormones; T and T have a relative potency of ~1:4 (T4:T3). T and T act on nearly every cell of the body, but have a particularly strong effect on the cardiac system. As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status. Prior to the development of levothyroxine, Thyroid, porcine or desiccated thyroid, used to be the mainstay of treatment for hypothyroidism. However, this is no longer recommended for the majority of patients due to several clinical concerns including limited controlled trials supporting its use. Desiccated thyroid products contain a ratio of T4 to T3 of 4.2:1, which is significantly lower than the 14:1 ratio of secretion by the human thyroid gland. This higher proportion of T3 in desiccated thyroid products can lead to supraphysiologic levels of T3 which may put patients at risk of thyrotoxicosis if thyroid extract therapy is not adjusted according to the serum TSH.