For many years, there has been a controversy concerning the most appropriate way to administer thyroid-hormone replacement therapy. Current thinking among conventional endocrinologists is that L-thyroxine (T4) should be used alone. T4 has a long half-life and is slowly converted in the body into the more biologically active triiodothyronine (T3). Thus, T4 therapy is said to provide smooth delivery of both T3 and T4, without the ups and downs that might occur by administering the more powerful and shorter-acting T3. The vast majority of physicians follow this approach of giving T4 alone to hypothyroid patients.

However, a growing minority of doctors, many of whom practice so-called alternative medicine, are not convinced that T4 alone is the way to go. In the first place, the human thyroid gland secretes at least three different iodinated compounds: T4, T3, and diiodotyrosine (DIT). Those of us who believe that nature does things for a reason have a
difficult time accepting the idea that a normally functioning thyroid gland does not know what it is doing. This believe-in-your-thyroid-gland philosophy is bolstered by the clinical observation that some hypothyroid patients whose symptoms fail to respond to T4 alone have a rapid and marked improvement when their treatment is changed to an equivalent dose
of thyroid extract (such as Armour thyroid).

A recent study supports the point of view long held by members of the alternative-medicine community. A group of Spanish researchers demonstrated that when rats were thyroidectomized and treated with T4 alone, their plasma and tissue concentrations of T4 were restored to normal. However, T3 levels in plasma and in most tissues remained low and
plasma concentrations of thyroid-stimulating hormone (TSH) remained elevated (indicating hypothyroidism) unless T3 was also given. Administering the combination of 0.9 mcg of T4 and 0.15 mcg of T3 per 100 g of body weight per day resulted in normal T4 and T3 concentrations in plasma and all tissues, as well as normal circulating TSH levels.

Whether DIT also has an important biological function is not known and was not addressed by this study. However, according to the late Dr. John Myers (of Myers’ ****tail fame), DIT is effective in the treatment of fibrocystic breast disease. In addition, one report from the 1940’s indicated that DIT is of value in the treatment of thyrotoxicosis.

What this study appears to suggest is that hormone-replacement therapy should be designed to mimic the body’s own glandular function as closely as possible. Although that point seems to be intuitively obvious, modern medicine has incorporated into its belief system the idea that doctors can improve upon nature by fractionating it; sort of like the idea that white bread and ‘managed care’ are good for your health. However, the study from Spain should remind us that it is difficult to improve upon nature.

We still have a lot to learn about the best way to administer thyroid hormones. For example, since the oral absorption of T3 is faster than that of T4, administration of thyroid extract or a T4/T3 combination such as Euthroid might produce transient unwanted elevations of T3 levels, resulting in a daily stress to the system. Even natural thyroid secretions might exert a slightly different effect when given orally than when the same hormones are secreted by the thyroid gland directly into the bloodstream. Perhaps additional research will tell us what the optimal proportions of T4, T3, and DIT are for oral administration. However, until all of the information is in, we should continue to make our best guesses. Mine is usually thyroid extract. For patients who do not respond to or do not tolerate thyroid extract, I usually prescribe a combination of synthetic T4 and T3. Given the rapid absorption of T3, putting this compound in a time-release base might be advisable.

Alan R. Gaby, MD

Recommended Reading:
1. Escobar-Morreale HF, et al. Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology 1996;137:2490-2502.

2. Escobar-Morreale HF, et al. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats. J Clin Invest 1995;96:2828-2838.

3. Barnes BO, Galton L. Hypothyroidism: the Unsuspected Illness, Crowell, New York, 1976.