T4 PLUS T3, AGAIN

Biondi B, Wartofsky L. Combination treatment with t4 and t3: toward personalized replacement therapy in hypothyroidism? J Clin Endocrinol Metab. 2012 Jul;97(7):2256-71.
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.
COMMENT- This article is presented just to alert any interested party to this very nice, and thorough, review of the possible benefits of T4+T3 therapy. The authors conclude that T4 mono-therapy probably does leave certain patients clinically not normal, in line with biochemical observations. All said and done, the evidence remains “iffy”, but who knows? Maybe further progress in micro-endocrinology will really prove the concept that some patients need T4 plus some T3. It is a careful and enjoyable read and synthesizes a huge amount of data. L De Groot, MD