Levothyroxine and Liothyronine in Hypothyroidism: A Comparative Review of Safety and Efficacy

Hypothyroidism is one of the most prevalent endocrine disorders worldwide and represents a major clinical and public health challenge due to its diverse systemic manifestations. Epidemiological data from the National Health and Nutrition Examination Survey indicate that approximately 4.6%of the United States population is affected. With higher prevalence among women and the elderly. 1,2 The condition arises from deficient production of thyroid hormones and is regulated through the hypothalamic-pituitary-thyroid (HPT)axis, involving coordinated secretion of thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), and the peripheral conversion of thyroxine (T4) to the biologically active triiodothyronine (T3).3,4 Thyroid hormone plays a crucial role in maintaining basal metabolic rate, cardiovascular function, thermoregulation, lipid and carbohydrate metabolism, and neurodevelopment. Levothyroxine (LT4) monotherapy remains the standard of care and is effective in achieving biochemical euthyroidism in the majority of patients.6 However, a subset of individuals continues to experience persistent symptoms despite normalized thyroid function test, leading to interest in alternative therapeutic strategies. Combination therapy with LT4 and liothyronine (LT3) has been investigated in multiple clinical trials, with mixed results regarding symptomatic improvement and quality of life. At present, such combination therapy is considered experimental and has not been approved by the US Food and Drug Administration. This review summarizes the epidemiology, physiologic basis, clinical manifestation, and current management strategies of hypothyroidism, with particular emphasis on emerging evidence surrounding combination hormone therapy and its potential role in selected patient populations.12