Hypothyroidism is a common endocrinopathy, and levothyroxine is commonly used to treat it. Despite agreement on the basic concepts of starting and modifying levothyroxine, there are many subtleties and complications to continuously sustaining euthyroidism. Understanding the influence of patient weight and residual thyroid function on initial levothyroxine dose, as well as taking age, comorbidities, thyrotropin target, life stage, and quality of life into account when levothyroxine is adjusted, was difficult and ever-changing. 

Because levothyroxine is a long-term drug, it was critical to prevent hazards associated with periods of overtreatment or undertreatment. Therefore, cases stemming from all areas of the patient’s life (coexisting medical disorders, stresses, lifestyle, psychological variables) should be explored extensively for the subset of patients who have not returned to baseline health with levothyroxine. If such variables did not appear to be a factor and biochemical euthyroidism had been effectively maintained, a trial of combination treatment with levothyroxine and liothyronine might be beneficial. 

Most randomized clinical trials did not support this, although other research with lower-quality evidence and animal studies might. Given the disparity, it was critical that any combination therapy trial be sustained only for as long as a patient benefit is obtained. In addition, it was crucial to monitor for side effects, especially in elderly or weak persons, and combination treatment should not be taken during pregnancy. A sustained-release liothyronine formulation has passed phase 1 testing and will soon be ready for better-designed and powered trials to determine if combination treatment is superior therapy for hypothyroidism.