Focus on Research

Archived Article – The Thyroid Society (1998 – 2003)

Over 100 years ago, Dr. George Murray first treated hypothyroid patients with a crude extract of sheep thyroid that contained both forms of thyroid hormone, the longer acting T4 and shorter acting T3. This breakthrough medication provided the first specific hormone replacement therapy for a hormone deficiency condition. For over 50 years, this combination of hormones was the standard treatment for hypothyroidism. However, several scientific findings led physicians to switch to synthetic T4 (thyroxine) as the treatment of choice.

First, it was discovered that most of the T3 circulating in the blood is derived from T4 rather than direct synthesis by the thyroid gland. Second, patients treated with products containing T3 often spent the first few hours after taking the drug mildly hyperthyroid, experiencing palpitations or rapid heart beats. However, when patients are treated with T4 only, the blood levels of T4 and T3 tend to stay fairly constant during a 24-hour period—with T4 concentrations toward the upper end of the normal range, and T3 concentrations toward the lower end of normal.

Nevertheless, there remain some patients who believe that they do not feel as good as they did before they had a thyroid problem at all. And some patients insist that they feel best when taking a T4-T3 combination such as thyroid extract. In a February 1999 article in New England Journal of Medicine, a group of investigators from Lithuania tested the hypothesis that a fixed combination of the two hormones might improve patient well-being and psychological functioning.

They randomly assigned 33 hypothyroid patients to be treated with either T4 at their usual dose or a lower dose of T4 combined with 12.5 micrograms of T3 for five weeks. At the end of the treatment period, patients were carefully studied and underwent a battery of psychological testing. Then, each of the patients switched from one drug regimen to the other, for a so-called “crossover study.” After patients completed another five-week period of treatment, they underwent the same group of tests. When all of the results were analyzed, the authors found that patients had improvements in mood and short-term memory, along with a slightly higher pulse rate, when they were treated with T3 in addition to T4.

So, should all hypothyroid patients go back to being treated with a T4-T3 combination as a result of this study? Probably not. First, a careful reading reveals several major flaws in what is called the study design. Half of the patients in the study were hypothyroid due to treatment for thyroid cancer, and as a result, many of the patients had been intentionally treated with higher doses of T4 to maintain their TSH level below normal. Therefore, some of the patients were actually hyperthyroid when they started in the study. Then, many of the patients’ TSH levels became undetectable during the study.

Since the patients in the study all went through changes in their thyroid hormone levels compared with the beginning of the study, a comparison should have been made with the results of testing performed at the beginning of the study, before any changes occurred at all; alas, this was not done. Finally, the treatment periods probably should have been separated by at least a month, to make sure that the effects of one drug treatment did not carry over and affect the outcome of the second drug treatment.

Nonetheless, the idea that some patients may do better with a T4-T3 combination remains a good concept. This article, like many important research studies, raises more questions than it answers. Hopefully, additional studies will be done that can answer these questions, avoiding the study flaws in this initial research effort.

In May, The Thyroid Society for Education & Research announced the recipient of the first Clinical Thyroid Research Stipend for Students in the Health Professions. Lesley L. Williams, a medical student at the University of Kentucky, will receive $2,500 to support her work on the project entitled Iodinated contrast dye effects: Duration of interference with iodine transfer studies. This new research support program has been created to encourage young physicians- and nurses-in-training to develop interest in thyroid disease and the problems of thyroid patients. These stipends have been partially underwritten by Knoll Pharmaceutical and Kronus, as well as the many con-tributors to the operating fund of The Thyroid Society.


Find more archived articles  from The Thyroid Society (1998 – 2003) below:

Fine Needle Aspiration Biopsy

Focus on Research

Thyroid Screening

Iodine Deficiency

Post Partum Thyroiditis

Postpartum Thyroiditis – Roller Coaster Ride for New Mothers

Thyrogen Advisory Panel, NDA 20-898

Thyroid Eye Disease

The Role of Nuclear Medicine In Thyroid Disease

Congenital Hypothyroidism

Donna Morgan

Donna Morgan

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