Thyroid Hormone

Adapted and updated from the book Resetting the Clock,

The thyroid is an important part of your glandular system. It maintains your body's temperature and controls the production of energy in your cells. If your thyroid malfunctioned too wildly, you'd simply die. Some people with that problem do, you know.

Thyroid hormone can't be regarded as a pro-longevity hormone, but the thyroid does affect how your other hormones work. If your thyroid is out of kilter, then the energy factory in every cell in your body is functioning less efficiently. You're healing less efficiently, constructing new protein less efficiently, and making use of your other endocrine hormones—the pro-longevity hormones—very poorly.

Let's consider what can go wrong with your thyroid, because if you're doing everything else right and you're still not feeling good, there's a very good chance that abnormally high or low thyroid function at the cellular level is the culprit. Up to 20 percent of people over sixty years old have thyroid problems — women more commonly than men. An appallingly high percentage is undiagnosed. According to current estimates, an estimated 27 million Americans have thyroid disease, and about 13 million of them are undiagnosed.

HIGH OR LOW

Thyroid hormones are produced in the thyroid gland, in the front of the neck, just under the Adam's apple. The pituitary gland controls production by its secretion of thyroid stimulating hormone (TSH), which increases or decreases according to perceived need. The pituitary gland in turn is triggered by thyrotropin releasing hormone (TRH), which is released by thyroid sensors in the hypothalamus at the base of the brain.

Thyroid hormone can become excessive because of a tumor on the thyroid or pituitary gland or because of an immune system imbalance. The body can produce and immune related globulin that mimics the action of TSH. When thyroid hormone is abnormally high, nervousness results with excess sweating, tremors, weakness, weight loss, and sometimes a bulging of the eyes. This condition is known as thyrotoxicosis, also called Grave’s disease, and can even cause heart failure and disorders of heart rhythm.

The more common thyroid disorder, however, is a deficiency. This can be caused by an allergic reaction, really a form of autoimmune disease. Viral infections can also destroy thyroid function. But, in many cases, thyroid activity declines to abnormally low levels without any obvious cause except advancing age. Diagnosis and treatment can sometimes be very subtle and time consuming.

Low thyroid—hypothyroidism—causes sluggishness and low energy. Body temperature goes down, weight gain is common, and fluid retention occurs. Generally, the victim of this condition exists in a state of chronic fatigue, and, in extreme cases, the outcome can be coma and death.

In the majority of cases, such disorders are relatively easy to diagnose using common laboratory blood tests of thyroid hormone and TSH levels. If such a deficiency is measured, a doctor will prescribe thyroid hormone tablets taken by mouth. Some practitioners prefer to use tetra-iodothyronine, abbreviated T4 (Synthroid® or Levoxyl®, other prefer replacenent with natural, desiccated thyroid extract (Westhroid® or Armour® thyroid) to provide a bit of di-iodothyronine, abbreviated T2, and tri-iodothyronine abbreviated T3. Some patients do very well receiving only T4 replacement. Others do better with natural desiccated thyroid extract, which has 20 percent T3.

Professionally accepted standards of practice in the medical community use laboratory measurement of pituitary derived thyroid stimulating hormone (TSH) as the gold standard for diagnosing hypothyroidism. If T3 is low at the cellular level, sensors in the brain signal the pituitary to release more TSH. High TSH is therefore a sensitive test for hypothyroidism. TSH can be misleading however, if the brain is converting more T4 to T3 than cells elsewhere in the body. In that case, TSH might remain normal but only the hypothalamus in the brain is adequately converting T4 to active T3. T4 can also be at a normal level, while conversion to active T3 remains sluggish.

As you can see, diagnosis and optimal treatment may require some trial and error, which can be time consuming because of several weeks delay to clinically experience the results of each change in dose or medication.

WHAT IF YOUR TESTS ARE NORMAL?

Unfortunately, it's quite possible to get back normal laboratory tests and still have symptoms of hypothyroidism, including low body temperature, chronic fatigue, and just not feeling up to par. This is sometimes called functional hypothyroidism and is not recognized and even disparaged by many health care professionals. The problem may be that a normal amount of thyroid stimulating hormone can be released into the circulation, but the T4 thyroid hormone is not having its full effect at the cellular level.

To explain this we need to look more closely at the various thyroid hormones. Thyroid hormone is made in the body from an amino acid called tyrosine, which is obtained from dietary protein. On the most common form of thyroid hormone, there are four sites that bind to four iodine molecules, and it is therefore called tetraiodothyronine, or T4 for short.

Another form of thyroid hormone, which is four times as potent as T4, has only three iodine molecules and is called T3. Although the thyroid gland produces three times as much T4 as T3, the liver and other tissues in the body then convert T4 into T3 for maximum effectiveness within organs and at a cellular level. T3 is the most important hormone at the cellular level. The thyroid also produces di-iodothyronine, T2, and recent evidence points at a role for that form also.

We have only recently understood that there is also a third kind of thyroid hormone, really an anti-thyroid hormone. It is part of the body's mechanism for conserving energy. Normal thyroid hormone helps us to utilize energy. Under certain circumstances, however—famine and fasting are the most outstanding examples—the body wants to conserve energy, and it does so by lowering body temperature, lowering energy production, and, generally speaking, slowing us down. It does this by converting T4 not to T3 but to reverse T3, or "rT3." A mirror image of true T3, rT3, has an empty iodine receptor on the reverse side, which can bind tightly to thyroid receptors within cells, thus blocking the action of normal T3 by denying it landing zones. This may be what happens in what has come to be called the Euthyroid Sick Syndrome (ESS) or Non-Thyroidal Illness Syndrome, and remains poorly understood. Another name sometimes used for related conditions is Wilson’s Syndrome.

The effect produced is somewhat similar to hibernation, and clearly during a famine this decreased energy consumption might be precisely what allows you to stay alive. Highly efficient varieties of this famine response seem to be what makes it so difficult for some people to lose weight. Many people are thought to have a hereditary tendency toward sustained rT3 production, which dieting or illness activates. Lower energy production partly cancels out the effect of lessened caloric intake, and this lower metabolic rate may continue for some time even after the diet is over, causing a rebound weight regain.

Routine laboratory tests will not detect this abnormal ratio of rT3 to T3, although newer and more expensive tests are now available. Even testing for true T3 and rT3 does not always show effects of resistance to T3 at the cell level. Conversion of T4 to any form of T3 may also be blocked. A much easier test, which costs nothing, is to measure body temperature several times daily with an accurate clinical thermometer. If the average body temperature is consistently below 98 degrees Fahrenheit, then ESS caused by inappropriate conversion of T4 to rT3, or by increased cell resistance to both T4 and T3, may possibly be the cause. Other illnesses and other hormone deficiencies can do the same, however.

How to Test Thyroid for Potential Function Dysfunction Yourself

Obtain an accurate clinical thermometer made from glass. Glass thermometers containing mercury are being phased out because of environmental concerns. A new type of glass thermometer with a non-toxic metallic column is readily available. Electrical, digital, and color-stripe thermometers are not accurate enough for this purpose.

Take your temperature several times every day—during the part of the day when you are active. Wait for at least three hours after you are out of bed in the morning before you take the first reading and take an additional two readings at least three hours apart. Hold the thermometer in your mouth, under your tongue, for at least five minutes. Keep your mouth completely closed while the thermometer is inserted. Do not eat or drink anything for at least twenty minutes prior to taking your temperature. You want the inside of your mouth to reflect your core body temperature, not what you recently put into it. Breathing through the mouth causes evaporation and cooling.

Write down each reading to the nearest tenth of a degree. Women should not do this during the three days prior to or during their menstrual period because the temperature is often higher then. Also, your readings should not be done during an acute illness or on days when you are unusually inactive.

Average the three readings for each day (add the three readings together and divide by three). Do this on seven different days. They do not have to be consecutive days.

If the average of the three readings for five or more of the seven days is below 97.8 degrees Fahrenheit, your metabolism is definitely slower than normal and you might have either an absolute deficiency of thyroid hormone, have ESS from producing too much rT3 relative to T3, be converting too little T4 to T3 in the body, or have so-called Wilson’s syndrome. These conditions are not fully understood. Laboratory testing is available to help with a more accurate diagnosis and rule out an absolute deficiency of T4 production by the thyroid gland—classical hypothyroidism. A trial of thyroid hormone in safe replacement doses may help to determine what works best in your particular case.

If repeated measurements show that your body temperature is consistently low and the usual lab tests are normal, you may want to get the more expensive lab tests mentioned above so that your health care practitioner can determine your precise levels and ratios of T4 toT3 and rT3. The ratio of T3 to rT3 is best ten-to-one or higher. If your ratio is lower than that and your body temperature is consistently low, there's an possibility that you've found your problem. Even if that ratio is normal, treatment with thyroid hormone replacement may help.

Natural desiccated thyroid extract (Westhroid® or Armour®), containing both T4, T3 and T2 has been reported to work better for some people than more commonly prescribed T4 alone (Synthroid® or Levoxyl®).

Just as most of the pro-longevity hormones decrease with age, it now appears that the conversion ofT4 to rT3 increases with age, partially blocking normal thyroid activity in some people. Major stress, such as that resulting from surgery, clinical depression, serious infection, or severe psychological stress can also trigger an increased production of rT3. It has been reported that this condition may become permanent, in which case the body does not return to its normal ratios after the precipitating stress has passed.

In most cases, the problem is merely an inability of the thyroid gland to produce enough thyroid hormone. Routine laboratory testing is adequate to make that kind of diagnosis. In such situations, the best answer is usually long-term, if not lifetime, treatment with thyroid hormone replacement.

WARNING: Excessive doses of thyroid hormone can cause osteoporosis and abnormal heart rhythm (atrial fibrillation). A safe replacement dose will cause laboratory measurement of TSH into the mid-range. If TSH is too close to the lower limit (as with sub-clinical hyperthyroidism), the replacement thyroid hormone dose may be too high.

Thyroid problems—as this short introduction may already have convinced you—form an intensely complex area of medicine that is not fully understood. But if you do have an over- or under-active thyroid, you will not feel physically well until the problem is fixed. Active energy-consuming creatures such as we are can never feel right with a broken thermostat or with the internal metabolic furnace turned down.

Selected References

Bunevicius R, Prange AJ. Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism. Int J Neuropsychopharmacol. 2000 Jun;3(2):167-174. Evidence that hypothyroid patients feel better with natural thyroid extract as replacement therapy.

Leary SC, Barton KN, Ballantyne JS. Direct effects of 3,5,3'-triiodothyronine and 3,5-diiodothyronine [T2] on mitochondrial metabolism in the goldfish Carassius auratus. Gen Comp Endocrinol. 1996 Oct;104(1):61-6. Research showing that T2 found in natural thyroid extract is a metabolically active iodothyronine hormone.

DeGroot LJ. The Thyroid and its Diseases, Chapter 5b The Non-Thyroidal Illness Sydrome, 2005 A textbook chapter describes the Euthyroid Sick Syndrome (ESS).

Hennemann G, Vos RA, de Jong M, Krenning EP, Docter R. Decreased peripheral 3,5,3'-triiodothyronine (T3) production from thyroxine (T4): a syndrome of impaired thyroid hormone activation due to transport inhibition of T4- into T3-producing tissues. J Clin Endocrinol Metab. 1993 Nov;77(5):1431-5. Reverse T3 (rT3) production blocks normal benefits of thyroid hormone.

Blanchard K, Brill MA. What Your Doctor May Not Tell You About Hypothyroidism: A Simple Plan for Extraordinary Results A medical doctor writes a book for the lay reader on this subject.

Abe E, Sun L, Mechanick J, Iqbal J, Yamoah K, Baliram R, Arabi A, Moonga BS,
Davies TF, Zaidi M. Bone loss in thyroid disease: role of low TSH and high thyroid hormone. Ann N Y Acad Sci. 2007 Nov;1116:383-91. Report that over-replacement of thyroid hormone increases risk of osteoporosis.

Duggal J, Singh S, Barsano CP, Arora R. Cardiovascular risk with subclinical hyperthyroidism and hypothyroidism: pathophysiology and management. J Cardiometab Syndr. 2007 Summer;2(3):198-206. Low TSH associated with 3 times the likelihood of atrial fibrillation over a 10-year follow-up