What is the best treatment for hypothyroidism?
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
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
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.