Abstract
Hypothyroidism is a common endocrinopathy, and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed on, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, comorbidities, thyrotropin goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. Because levothyroxine is a lifelong medication, it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient's life (coexistent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower-quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy be continued only as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be used during pregnancy. A sustained-release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.