Therapeutic use of triiodothyronine in hypothyroidism: Current status and the road ahead

Hypothyroidism is a common endocrine disorder affecting 1%–10% of the population. To date, levothyroxine (LT4) monotherapy is the standard of care in the management of hypothyroidism. However, approximately, 5%–10% of patients who normalize thyroid-stimulating hormone levels with LT4 monotherapy may have persistent symptoms that clinicians may attribute to tissue hypothyroidism. A long-standing debate in the literature iswhether the addition of levotriiodothyronine (LT3) to LT4 will ameliorate lingering symptoms. However, patients with hypothyroidism who have persistent symptoms despite the exclusion of other comorbid conditions or nutritional deficiencies and patients with specific genetic mutations in deiodinase enzyme may respond to a trial of LT3 alone or in combination with LT4 therapy. This article intends to review the current literature available to understand the drawbacks of thyroxine (T4) monotherapy, establish the concept of T3 + T4 combination therapy, its safety and efficacy based on evidence, recommendations from guidelines, and its implications.