Experimental and clinical evidence suggests that a TSH level within the reference range is not a sufficiently optimal marker of adequate thyroid hormone replacement therapy in hypothyroid patients… Conceivably, four different groups of hypothyroid patients could benefit from combination treatment with T4 and T3: 1) patients with hypothyroidism due to an under- lying autoimmune condition (38, 64, 65); 2) thyroidectomized patients or patients submitted to radioiodine activities resulting in a lack of sufficient endogenous thyroid function and absence of residual thyroidal T3 production (36); 3) patients with certain D2 polymorphisms (the enzyme responsible for T3 tissue availability) who tend to have a preference for combination T4/T3 replacement therapy (66, 67); and 4) depressed hypothyroid patients who might benefit from the antidepressant effect of lio-thyronine (68)…


Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic.
We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action.
The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients.
Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.