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JAMA Publishes New Research Saying T3 Offers No Benefit

Updated June 10, 2015.

by Mary Shomon

December 11, 2003 ? The use of the thyroid drug triiodothyronine ? also known as T3 -- as an adjunct to levothyroxine (T4) therapy has been dealt another blow by the research community in an article published in the December 10, 2003 issue of the Journal of the American Medical Association (JAMA) (Clyde, Patrick W. e. al. ?Combined Levothyroxine Plus Liothyronine Compared With Levothyroxine Alone in Primary Hypothyroidism: A Randomized Controlled Trial? Journal of the American Medical Association. 2003;290:2952-2958) The study was conducted by a joint team of researchers from the Naval Medical Centers in Bethesda, MD and San Diego, CA.

By way of background, the recommended hormone replacement therapy for the treatment of hypothyroidism since the 1960s was synthetic T4 given alone. This therapeutic approach was challenged in 1999 with the publication of the famous Prange/Bunevicius study, which appeared in the New England Journal of Medicine. (NEJM) Patients receiving combined synthetic T4 plus T3 treatment performed better on a variety of standard neurophysiological tasks. There also was an improvement in the psychological state of these patients. When asked at the end of this study which treatment they preferred, twenty said they preferred the synthetic T4 plus T3 treatment, eleven had no preference, and only two preferred T4 alone. Patients who preferred the combined T4 plus T3 treatment reported that they had more energy, improved concentration, and felt better overall. This led researchers to state that ?treatment with thyroxine plus triiodothyronine improved the quality of life for most [hypothyroid] patients.? The researchers also recommended that the ideal thyroid hormone replacement program for someone without a thyroid gland, or whose thyroid gland is nearly non-functioning, would be 10ug of T3 daily in sustained-release form?along with enough T4 to ensure euthyroidism.

This NEJM study appeared to provide a research basis behind the growing practice of using supplemental T3 for hypothyroid patients who had persistent symptoms despite so-called ?normal? blood tests on T4 alone.

The newly published JAMA study was designed to avoid some of the shortcomings associated with the 1999 NEJM study. A study design was used that avoided the possibility of a ?practice effect? (patients scoring better due to repetition/practicing) on the mental functioning tests. Most of the forty-six patients in this study had hypothyroidism resulting from autoimmune thyroid disease (Hashimoto?s Disease). In the JAMA study, the two groups of patients either continued to receive their current synthetic T4 dose or received 50 µg less of their current dose of T4 plus 7.5 µg of T3, twice daily. The synthetic T4 doses of patients in both groups were adjusted to keep patients at so-called ?normal? thyroid levels, according to blood tests.

After four months, there were no differences in body weight, blood pressure, or lipid levels between the two groups of patients after this four-month study. Additionally, no significant differences were observed in any of the standardized tests that assessed hypothyroidism symptoms or mental function.

This led researchers to conclude that ?compared with levothyroxine alone, treatment of primary hypothyroidism with combination levothyroxine plus liothyronine demonstrated no beneficial changes in body weight, serum lipid levels, hypothyroid symptoms?and standard measures of cognitive performance??

The JAMA study echoes the findings of two studies reported on in the October 2003 Journal of Clinical Endocrinology and Metabolism.

In one of the JCEM studies, the effectiveness of combination T4/T3 treatment was studied. ( Walsh et. al. "Combined Thyroxine/Liothyronine Treatment Does Not Improve Well-Being, Quality of Life, or Cognitive Function Compared to Thyroxine Alone: A Randomized Controlled Trial in Patients with Primary Hypothyroidism," The Journal of Clinical Endocrinology & Metabolism, Vol. 88, No. 10 4543-4550)

In this study, 10 µg of T3 was substituted for 50 µg of the patients? usual synthetic T4 dose. The double-blind, random order, crossover trial compared the impact of the two treatments on quality of life, cognitive function and subjective satisfaction in 110 hypothyroid patients. In this study, approximately one-half of the subjects received T4 therapy for 10 weeks and then T4 and T3 therapy for 10 weeks. The other half of the subjects received the combination therapy first. The researchers found no significant benefits for combination therapy compared to T4 alone. However, they did find that anxiety and nausea were significantly worse for patients on the combined therapy.

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