In this review, researchers discuss the physiological mechanisms and rationale for the potential role of combined T3 and T4 therapy in hypothyroid patients. They first examine the complex feedback interaction between central hypothalamic control and the production and release of thyroid hormones to the periphery. Moreover, they discuss the intricacies underlying thyroid hormone metabolism by explaining the importance of deiodinases for tissue euthyroidism and the clinical consequences of some deiodinase polymorphisms. Subsequently, the will reassess the results of the available studies and review articles on combined treatment, examining the design of each study, the category of patients selected for this treatment, theT4/T3 ratio, the duration of this therapy, the levels of free thyroid hormone and TSH during the two regimens of replacement therapy (monotherapy vs. combined therapy), and the effects at the tissue level. This evaluation may help identify patients who could benefit from combined therapy, the sensitivity of some tissue parameters, and the potential physiological reasons why specific organs could be more sensitive to T3 than to T4. They believe that the complexities inherent in their analyses should reopen the controversy on the potential merits of combined therapy. The analysis may allow clinicians to consider alternative explanations for the lack of beneficial effects in past investigations and hopefully spur more research on this issue.
Biondi B, Wartofsky L. Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism? Journal of Clinical Endocrinology & Metabolism. http://jcem.endojournals.org/content/early/2012/05/15/jc.2011-3399.abstract (Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?)
Context: 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 T3 and T4 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.
Evidence Acquisition: 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 T4/T3 ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action.
Evidence Synthesis: The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients.
Conclusions: 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.
Biondi B, Wartofsky L. Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism? Journal of Clinical Endocrinology & Metabolism. http://jcem.endojournals.org/content/early/2012/05/15/jc.2011-3399.abstract (Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?)
Context: 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 T3 and T4 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.
Evidence Acquisition: 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 T4/T3 ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action.
Evidence Synthesis: The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients.
Conclusions: 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.
