Before we start understanding conversion, let’s take a look at the physiology of how the thyroid gland works. When your body senses that your thyroid hormone level is low, the hypothalamus tells the pituitary gland in the brain to produce TSH (thyroid stimulating hormone). TSH tells the thyroid gland to start producing more thyroid hormones. This gland then produces 7% T3 (the active thyroid hormone) and 93% T4 (the inactive one). These hormones are converted to T3 and reverse T3 (rT3) in the liver, gut, and peripheral tissues.
When we have increased stress levels, your body produces cortisol.
Cortisol (your stress hormone) blunts the TSH. In addition, more reverse T3 hormones (inactive thyroid hormone) are produced. This, in turn, binds to the receptor sites where T3 normally would sit. Reverse T3 is inactive which can result in hypothyroid issues.
Initially, we have a T4 molecule which has 4 iodine molecules bound to it. There is an enzyme called 5’ deiodinase that removes one of the iodine particles. As a result, the process creates T3 (the active thyroid hormone). When we have increased stress or prolonged stress, the body actually produces more reverse T3 to respond to that stress. Another enzyme called 5 deiodinase creates reverse T3. This reverse hormone takes the iodine off the opposing side of the molecule.
If you look at both T3 and rT3 particles, they look very similar. In fact, they almost look like mirror images of each other. But when reverse T3 binds to the receptor sites in the cell, it’s actually an inactive thyroid hormone. It takes up the receptor and makes it so we don’t have space for the active thyroid hormone (T3) to stimulate the cell to increase metabolism. So, when we see that increase in stress, we can actually see how reverse T3 starts to increase.
So, how do we know if we have too much reverse T3 in our system?
There are a couple of good equations from where you can take your lab values and plug them in. We have free T3 divided by reverse T3. This ratio should be greater than 20. And if you want to use just regular T3, protein bound, it’s total T3 divided by reverse T3, which should be greater than 10.
- fT3/rT3 ratio: >20
- T3/rT3 ratio: >10
What causes a reduction in the conversion from T4 to T3?
Stress is a big problem because it can change your cortisol levels. Either decreased or increased amounts of cortisol in your system can cause a problem with conversion of T4 to T3. It can also minimize the effect of TSH on the thyroid itself, thereby reducing the actual formation of thyroid hormone.
Gut bacteria is very important in the conversion of T4 to T3. When you have an imbalance between the good and the bad bacteria in the gut, this may significantly reduce the conversion. This will then cause inflammation in the gut. When this happens, it reduces T3 by raising cortisol.
There are many medications that can slow down the conversion of T4 to T3. Amiodarone is a medication typically given for tachycardia and other heart-related issues. Corticosteroids can be a big factor as well.
Inflammation and infections can also cause a problem. When we start to see an increase in CRP (C-reactive protein), we see reduced tissue levels of T3. Gluten or grain can create problems because of inflammation in the gut. This inflammation can be a contributor to celiac disease as well. When we see an increased inflammatory response, we can also see a reduction of conversion.
Birth control pills contain different amounts of estrogen and progesterone in synthetic forms. When we see an increase in estrogen, we can observe a problem with conversion from T4 to T3. Bisphenol A, found in plastics, is also a synthetic estrogen which can have the same effect.
Did you know just about all our rice has arsenic in it? Go to the FDA website and take a look and you’ll see. Rice is one of those important things that we need to be careful of – you may not want to eat it every day. Exposure to arsenic can increase inflammation and therefore reduce T4 to T3 conversion.
Persistent organic pollutants or POPs can be anything from pesticides (which you’re bombarded with every day) to toxins in the air or fluids that we’re drinking. These pollutants are a big issue, and the minimal problem that we have is the conversion of T4 to T3. Be very careful of exposures to these toxins.
Speaking of exposures, fluoride is added to our water without your consent. Fluoride and bromide look a lot like iodine, and therefore, can start to bind in place of iodine in thyroid hormones. This creates inflammation that leads to the reduction, conversion, and even formation of thyroid hormone itself.
Liver and kidney functions are highly crucial in conversion.
With so much of the conversion happening in the liver, you cannot convert if you have liver disease. However, you can produce the proteins that transport thyroid hormone throughout the body.
Kidney function is important because these organs are responsible for some of the deiodinase enzymes. These enzymes remove iodine from T4 to form T3 or reverse T3.
Insulin can create an increase in inflammation which can reduce the conversion of T4 to T3. On the other hand, iron reduction can cause anemia which can compromise the conversion of T4 to T3.
There are various things that can enhance conversion.
- Selenium is very important for the deiodinase enzymes – those enzymes that are responsible for removing the iodine from T4 to create T3 or reverse T3.
- Zinc is required for the healthy production of T4 and healthy T3 receptors in your cells.
- Iron is required for thyroid hormone production and the conversion of T4 into T3 and for the best utilization of T3 inside the cell.
- Vitamin A is important for the thyroid hormone receptors because it activates genes and regulates TSH.
- Vitamin D is probably one of the most important things that you can take to reduce inflammation. This can support the immune system functions as well. It’s almost not considered a vitamin anymore but a hormone. Make sure you have proper amounts of vitamin D to help conversion from T4 to T3 as it reduces inflammation.
- Vitamin C has quite a high antioxidant value. Antioxidants have been shown to reduce free radical formation. Vitamin C is also high in the adrenal glands which handle stress.
- Vitamin B can be depleted with an increase in stress. A deficiency can cause increased inflammation and therefore reduction of conversion of T4 to T3.
- Tyrosine is the backbone of the thyroid hormones along with iodine. This determines the activity of the hormone.
Let’s take a look at thyroid lab tests.
- The pituitary gland produces TSH or thyroid stimulating hormone. Its job is to tell the thyroid to speed up. I like this test because it helps me understand what the pituitary is doing and also how the thyroid functions are doing.
- T4 or total T4 reflects the total amount of inactive thyroid hormone bound to proteins. About 95-98% of thyroid hormones are bound to proteins or thyroid bonding globulin. These make up the total thyroid hormone. The remaining 2-5% is free and it isn’t bound to proteins. T4 is a good assessment of thyroid output.
- Free T4 (fT4) is the amount of T4 not bound to protein. It is more accurate and is not affected by protein levels.
- T3 or total 3 is the amount of T3 bound to protein.
- Free T3 (fT3) is the amount of T3 not bound to protein. Just like T4, it’s more accurate. Protein levels do not affect them. It is the most active thyroid hormone that we have.
- Reverse T3 (rT3) is an inactive hormone. Normally, 20% of T4 goes to the making of reverse T3. One problem is stress can increase or decrease the cortisol levels. This, in turn, increases reverse T3. Reverse T3 (inactive) can then bind to active hormone sites in the cell and cause hypothyroid issues.
- T3ru or T3 resin uptake is used to assess transport proteins and the ability to bind in the blood.
In addition to regular labs, we also need to look at autoimmune markers.
TGab or thyroid globulin antibody targets thyroglobulin. Thyroglobulin is a protein involved in T3 and T4 production. It can be ordered for hypothyroid or hyperthyroid evaluation and management.
- TPOab or thyroid peroxidase antibody is an enzyme that helps activate iodine during the creation of thyroid hormone. TPOab and iodine then assist tyrosine form the backbone of the thyroid hormone. This test is usually used if the person has Graves’ or Hashimoto’s disease.
- TSHrab (thyroid stimulating hormone receptor antibody measures the antibodies against the thyroid stimulating hormone receptor in the thyroid. This is present in Hashimoto’s and Graves’ disease as well.
- TSI or thyroid stimulating immunoglobulin binds to receptors and promotes the production of thyroid hormones. This eventually leads to hypothyroidism, as seen in Graves’ disease.
- TBII prevents thyroid stimulating hormone from binding to proteins in the thyroid gland. This test can be used to assess treatment for Graves’ disease.
Standard thyroid testing vs. advanced testing.
It’s common to hear from patients that they were told by their doctors that their labs look normal when all that was run was a standard TSH and T4. I agree that those two tests are important, but there is so much more to consider. When someone’s not using T4 to convert to T3, T3 will decrease while T4 backs up causing the T4 levels to be increased. And with those T4 levels increased, your TSH will decrease as well.
Because your body doesn’t think it needs any more thyroid hormone, this will cause your thyroid hormone production to be less. It thereby increases your hypothyroid issues. You may still see the same thyroid symptoms when taking a synthetic thyroid (such as Synthroid) because it is only T4.
Another issue is when you go to your doctor and they do a follow-up lab. They see a high T4 and don’t run a T3. As a result, they reduce your medication. Sometimes, this can be right and sometimes it can be wrong because higher levels of T4 may mean that you’re not converting.
Hypothyroidism can be a roller-coaster. There are also other issues with taking synthetic straight T4. Research shows that patients who take it have lower levels of T3. This can be a problem with medication or that the doctor didn’t order all the labs necessary to make a good decision. Either way, you, as a thyroid patient, now have a problem.
For most people, a bioidentical type of thyroid replacement hormone can really make a difference.
A bioidentical thyroid hormone replacement is very similar to what your thyroid puts out – T4 and a very small percentage of T3. But for other people like those with Graves’ disease and Hashimoto’s, T3 can really be a problem. So, it is important to run all these labs to further understand what kind of problem you’re dealing with so that the correct treatment can be implemented.
Let me know if I can help you understand your thyroid condition.