About 100 years ago, in 1891 to be exact, the British physician George Murray presented information on a patient with severe hypothyroidism who was successfully treated with injections of sheep thyroid extract. This was the dawn of a new era, in which patients with hypothyroidism no longer suffered needlessly from severe and incapacitating symptoms, or even occasionally died of their disease. Following Dr. Murray's report, others attempted giving the thyroid extract orally, either raw, with bread and butter (a thyroid sandwich), or even "lightly fried." By 1898, Sir William Osler, Chief of Medicine at the newly built Johns Hopkins Hospital and possibly the most famous physician in America, wrote:
"That we can restore to life the hopeless victims of myxedema is a triumph of experimental medicine…The results, as a rule are most astounding-unparalleled by anything in the whole range of curative measures."
In the early part of the 20th century, chemists figured out how to take minced animal thyroid glands and make an active extract that could be taken as a pill, a preparation called desiccated thyroid, which is still used by some patients to this day. In the 1920s the structure of thyroxine, the main thyroid hormone present in the thyroid gland, was unraveled. However, synthetic thyroxine, the form of thyroid hormone replacement which is most often used by patients today, was not commercially possible until the 1950s.
In the mid 1950s, a second thyroid hormone was discovered, called triiodothyronine or T3. T3 is so named because it contains 3 iodine atoms within its structure, rather than the 4 found in thyroxine (abbreviated T4). After T3 was found to be more active in regulating the body's metabolism than T4 itself, some drug companies began to manufacture thyroid hormone tablets that contained both T4 and T3, to ensure that patients received the benefit of both hormones. However, in the 1960s it was discovered that 80% of the T3 made daily by our bodies arises not from the thyroid but from the removal of one iodine atom from the T4 molecule. This conversion process, in which T3 is formed from T4, occurs mainly in the liver, but it takes place in other tissues as well. We now know that the thyroid gland itself only makes about 20% of the body's total daily T3 requirements. Once the fact that T3 was derived from T4 was recognized, pills that contained both T4 and T3 fell out of favor. Physicians realized that when a patient took pure T4 the patient's own body would convert the T4 into T3 in a regulated way that would be correct for that person.
Today, pure synthetic T4 is the medication that the vast majority of hypothyroid patients use. Most physicians now consider desiccated thyroid and the combinations of synthetic T4 and T3 to be obsolete. Since they contain both T4 and T3, and T3 is absorbed and used by the body more quickly than T4, their T3 content can cause some patients to develop temporary symptoms of hyperthyroidism (palpitations, nervousness) after a tablet is taken. Also, desiccated thyroid, derived from slaughterhouse animals, may have variable potency from batch to batch, depending on the animals' diet, the season of the year, and the species of animal used to make the tablets.
Synthetic T4 is now one of the top 3 or 4 most commonly prescribed medications in the United States. It is safe, effective, and inexpensive. However, physicians who see a lot of thyroid patients have recognized for years that occasional patients, perhaps one in a hundred, simply do not feel as well taking pure thyroxine as they do when taking either desiccated thyroid or one of the T4 and T3 combinations.
This background information takes us up to the present, and to a discussion of a recent article from an Endocrinology Clinic in Latvia that was published in The New England Journal of Medicine in February 1999. These investigators asked the question: do hypothyroid patients feel just as well taking pure T4 as they do when they are switched, without knowing it, to a combination of T4 + T3? The authors studied 33 hypothyroid patients who were randomly assigned to take either their usual dose of T4 for 5 weeks or to take slightly less T4 plus a small dose of T3, so that the total amount of hormone, from a biological standpoint, was the same. After 5 weeks, the patients were switched to the other thyroid hormone regimen. The assignment to a particular regimen was done in random order: some people took T4 first and other people took T4 + T3 first. The study was also "blinded" so that neither the patients nor the doctors knew whether they were taking T4 or the T4 + T3 combination. The patients were given a battery of psychological tests as well as questionnaires that assessed their mood. The tests were given after 5 weeks of their usual T4 dose and after 5 weeks of the T4 + T3 combination.
Compared to T4 therapy, the T4 + T3 therapy was associated with a slight rise in the pulse rate, but no differences in blood pressure or serum cholesterol. Certain cognitive tests, like the ability to recall a series of numbers or draw a certain shape from memory were slightly better with the combination of T4 and T3. Perhaps more importantly, measures of mood, especially depression, low energy, and anger was improved with the combined regimen. When patients were asked whether they preferred the first treatment or the second treatment (not knowing which was the T4 and which was the T4 + T3), 20 preferred the T4 + T3 combination, 11 had no preference, and 2 preferred the T4 alone.
What are we to make of these results? First, it is important to remember that the vast majority of patients feel well on their current thyroxine medication. There is absolutely no reason for anyone who is feeling well to switch to another preparation, especially until the results of the New England Journal study are confirmed by other scientists.
Also, as pointed out in a companion editorial in The New England Journal of Medicine, the form of T3 that is currently available for use is not ideal; it would be better to take T3 in a slow-release form to avoid side-effects like palpitations, but this is not available. In fact, one patient in the study had to be withdrawn because she developed anxiety when she took the combined T4 + T3 treatment.
Thyroid hormone therapy has undergone an evolution over the last century, from sautéed sheep thyroid to pure synthetic hormones. Although it may seem like things have gone full circle, back to desiccated thyroid or pills that contain T4 + T3, we have much more to learn before we will be ready to abandon a tried and true treatment that has been in use for over 50 years. But, if you are one of those rare hypothyroid patients who is not feeling quite right on T4, you should speak to your doctor about a therapeutic trial of T4 (in a lower dose) plus a small dose of T3. Ideally, it would be better if you could take the T4 + T3 in a blinded manner to avoid a placebo effect-that is, feeling better just because you are taking a new medicine. Of course this is impossible to do outside of a research study. The most important thing is to communicate with your doctor about how you feel, and to continue to learn as much as possible about your condition so that you can be an active participant in your health care.
How to Find the right Specialist.