Thursday, February 19, 2015

T3 and T4 - the two effective thyroid hormones

Hypothyroidism is a condition classified by an under-active thyroid gland—when the thyroid does not produce enough hormones. There are various treatments available, but the basic concept is the same—and it's known as thyroid hormone replacement therapy.
To best understand the purpose of thyroid hormone replacement therapy, you need to understand the interaction of T3 and T4—the two thyroid hormones. Both the thyroid and parathyroid glands are endocrine glands. This means they make and secrete (release) hormones. Hormones are chemicals which can be released into the bloodstream. They act as messengers, affecting cells and tissues in distant parts of your body. Thyroid hormones affect the body's metabolic rate and the levels of certain minerals in the blood. The hormone produced by the parathyroid also helps to control the amount of these essential minerals.

The full name of T3 is Triiodothyronine and T4's full name is Tetraiodothyronine or Thyroxine. T3 and T4 control your body's metabolism. If you don't have enough of them, then your metabolism slows down. Your metabolic rate dictates how quickly you process food, how fast your heart beats, how much heat your body creates—and even how quickly you can think. In essence, T3 and T4 are in charge of how your body uses energy.
T3 and T4 are not equal in strength; T3 is the more active hormone of the two. While T3 is stronger, taking synthetic T4 hormone is considered the standard treatment for hypothyroidism. The reason for this is because most of the T3 in our bodies actually used to be T4. When T4 hormones come into contact with other cells in the bloodstream, they give up an iodine atom to interact with those cells. When T4 loses an iodine atom, it becomes T3.

When this T4 into T3 conversion occurs, T3 then conveys the metabolic "message" to the other cells throughout the body. The benefit of taking only T4 therapy is that you're allowing your body to perform some of the actions it is meant to do, which is taking T4 and changing it into T3. The half life of T4 is also longer compared to T3 (7 days versus 24 hours), that means that it will stay for a longer time in your body after ingestion.

The thyroid makes three hormones that it secretes into the bloodstream. Two of these hormones, called Thyroxine (T4) and Triiodothyronine (T3), increase your body's metabolic rate. Essentially, the body's metabolic rate is how quickly the cells in your body use the energy stored within them. Thyroid hormones make cells use more energy. By controlling how much energy our cells use, thyroid hormones also help to regulate our body temperature. Heat is released when energy is used, increasing our body temperature. Thyroid hormones also play a role in making proteins, the building blocks of the body's cells. They also increase the use of the body's fat and glucose stores.

In order to make T3 and T4, the thyroid gland needs iodine, a substance found in the food we eat. T4 is called this because it contains four atoms of iodine. T3 contains three atoms of iodine. In the cells and tissues of the body most T4 is converted to T3. T3 is the more active hormone, it influences the activity of all the cells and tissues of your body.

The other hormone that the thyroid makes is called calcitonin. This helps to control the levels of calcium and phosphorus in the blood. These minerals are needed, among other things, to keep bones strong and healthy. Your thyroid gland is a small gland, normally weighing less than one ounce, located in the front of the neck. It is made up of two halves, called lobes, that lie along the windpipe (trachea) and are joined together by a narrow band of thyroid tissue, known as the isthmus. The function of the thyroid gland is to take iodine, found in many foods, and convert it into thyroid hormones: Thyroxine (T4) and Triiodothyronine (T3). Thyroid cells are the only cells in the body which can absorb iodine. These cells combine iodine and the amino acid tyrosine to make T3 and T4. T3 and T4 are then released into the blood stream and are transported throughout the body where they control metabolism (conversion of oxygen and calories to energy).

Every cell in the body depends upon thyroid hormones for regulation of their metabolism. The normal thyroid gland produces about 80% T4 and about 20% T3, however, T3 possesses about four times the hormone "strength" as T4. The thyroid gland is under the control of the pituitary gland, a small gland the size of a peanut at the base of the brain (shown here in orange). When the level of thyroid hormones (T3 and T4) drops too low, the pituitary gland produces Thyroid Stimulating Hormone (TSH) which stimulates the thyroid gland to produce more hormones. Under the influence of TSH, the thyroid will manufacture and secrete T3 and T4 thereby raising their blood levels. The pituitary senses this and responds by decreasing its TSH production. One can imagine the thyroid gland as a furnace and the pituitary gland as the thermostat.

The pituitary gland itself is regulated by another gland, known as the hypothalamus (shown in the picture above in light blue). The hypothalamus is part of the brain and produces TSH Releasing Hormone (TRH) which tells the pituitary gland to stimulate the thyroid gland (release TSH). One might imagine the hypothalamus as the person who regulates the thermostat since it tells the pituitary gland at what level the thyroid should be set.

Treatment of hypothyroidism:
After proper diagnosis of hypothyroidism, the next issue is with what substance to treat. The traditional approach is to use Synthroid/ Levoxyl/Levothroid (levothyroxine) which is only T4. Natural medicine doctors tend to use Armour thyroid which is a mixture of mono and di-iodothryonine and T3 and T4, the entire range of thyroid hormones.

If the Free T3 level is significantly lower than the Free T4 level, it is next to useless to treat with Synthroid/ Levoxyl/Levothroid (T4) only replacements. If the patient could not muster sufficient T3 from their gland (which produces some T3 directly), then they are certainly not going to convert enough T3 from T4 only. Traditional medicine assumes that preparations like Synthroid which are T4 only converts peripherally in the body to T3 in fairly standard amounts and at fairly standard rates. Unfortunately, clinical experience shows this is not true for the majority of patients. Consistent measuring of both free T3 and free T4 blood levels in hypothyroid patients who are on T4 only therapy will very rapidly dispel this myth. A certain percentage of hypothyroid patients do convert enough T4 to T3 at a sufficient rate for T4 treatment to be adequate as a source of T3; but a substantial proportion of patients require some combination of both exogenous T3 and T4.

Once on hormone replacement, the TSH remains useful until it goes BELOW 0.4. Then one has optimized thyroid function by the TSH yardstick; it then remains to optimize thyroid function by the yardstick of the accurate measures of the 2 thyroid hormones, the Free T4 and Free T3 levels.

So one should use a combination of T4 and T3 which compensates for the inability to convert T4 to T3. This is most frequently done with Armour thyroid. However, Cytomel, which is T3 only, can be used in combination with one of the T4 only preparations. It is important to recognize that T3 should always be prescribed twice daily due to its shorter half life. This is typically after breakfast AND supper for compliance reasons.

Taking the dose at these times overcomes traditional medicine's major objection and resistance to using natural thyroid preparations - its variability in its blood levels. Armour thyroid is desiccated thyroid and has both T3 and T4. Most doctors using Armour thyroid are not aware that Armour thyroid should be used twice daily and NOT once a day. The major reason is that the T3 component has such a short half life and needs to be taken twice daily to achieve consistent blood levels.

Once or twice daily dosing one can then optimize both the T4 and T3 levels, with whatever thyroid preparation is required. This is not possible in most hypothyroid patients with T4 only preparations. It is important to use a preparation with T3 because T3 does 90% of the work of the thyroid in the body. The only exception to pursue optimization of the T3 level without using Armour thyroid is in severe acute cardio-pulmonary conditions, when the metabolic slowing effect of a low FT3 level can actually be life-saving. However, the vast majority of hypothyroid patients do not have acute cardio-pulmonary conditions, such as congestive heart failure.

The most common starting dose for patients with hypothyroidism is Armour thyroid, 90 mg which is cut in half with a razor blade and half is taken after breakfast and the other half after dinner. Taking it after meals also helps to reduce volatility of the blood-level of T3. If the patient has any problem breaking or cutting the pill, they should purchase a pill-cutter at the pharmacy. The TSH, Free T3 and Free T4 are then repeated in one month and the dose is adjusted.

In order to optimize the hormone replacement, the Free T3 and Free T4 should be above the median but below the upper end of the laboratory normal reference range. The goal for healthy young adults would be to have numbers close to the upper part of the range, and for cardiace and/or elderly patients, the numbers should be in the middle of its range. The Free T3 and Free T4 levels should be checked every month and the hormone therapy readjusted until the FT3 and FT4 levels are in the therapeutic range described. A small number of large, overweight, thyroid-resistant women may need 6-8 grains of Armour Thyroid or the equivalent of thyroxine per day (counting 0.1mg of T4 as 1 grain of Armour Thyroid). Patients need to be warned about the overdosage symptoms which are frequently only temporary during the adaptation stage. The symptoms may include: palpitations, nervousness, feeling hot and sweaty, rapid weight-loss, fine tremor, and clammy skin. There is one exception to the 1.5 level of TSH as the cutoff for treatment. Overweight patients who have classic symptoms of hypothyroidism and have made heroic unsuccessful attempts to lose weight may benefit from thyroid hormone replacement even if their TSH slightly below 1.5 and FT4 and FT3 are not below their normal ranges. Since the only change will be in the FT3 level, which has a short half-life, the serum FT4 and FT3 levels (and TSH, if indicated) can be measured 48-72 hrs after the splitting of the doses if the patient had been on the hormone for 4-6 weeks before the splitting of the doses. This is because the T4 fraction is the one that takes a number of weeks to build up to its steady-state serum level.

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