Thyroid Thursday Episode 46: Thyroxine Binding Globulin
Thyroxine Binding Globulin
Welcome to another edition of Thyroid Thursday, in this post I want to clear up some confusion about this thing called thyroxine binding globulin, so I want to explain what that is.
Sometimes I get patients who are confused about what it is and how it is related to Hashimoto’s and thyroglobulin antibodies. Even Doctors get this confused at times when they are asked them to run thyroglobulin antibodies and they will wind up running thyroid binding globulins.
So, let’s talk about what thyroxine binding globulin (TBG) is. It should probably be just called thyroid hormone binding globulin since it binds and transports thyroid hormones not just thyroxine. It is NOT thyroglobulin. Thyroglobulin is the precursor to T4 and T3, the thyroid hormones, and it is found within the thyroid gland, thyroid binding globulin is a protein that binds thyroid hormone and carries it around the body (think taxicab). It binds to the thyroid hormones T4 and T3, that are released from the thyroid gland and escorts them to the tissues and cells of your body.
Thyroxine Binding Globulin is not what thyroglobulin antibodies attack in Hashimoto’s, thyroglobulin antibodies attack the thyroglobulin which is in the thyroid gland, thyroid binding globulin is made in the liver while thyroglobulin is made in the thyroid gland.
Thyroxine Binding Globulin is a carrier protein for a thyroid hormones T4 and T3. TBG can also transport reverse T3. Thyroxine Binding Globulin is the primary transport protein of thyroid hormones. There are two other transport proteins, transthyretin and albumin are two other molecules that are in higher concentrations in the serum that can bind T4, T3 and reverse T3 but they don’t have the same affinity or attraction power. Thyroxine binding globulin is the primary carrier hormone, about seventy five percent of the T4 and T3 in your serum is transported around the body by TBG.
FUNCTIONS OF THYROXINE-BINDING GLOBULIN
- It Safeguards Body From Fluctuations: When the thyroid gland makes T4 and T3, it releases it into the serum, these binding globulins (proteins) bind T4 and T3 and escort them around the body. TBG also has a capacity to hold on a certain amount of thyroid hormone in its inactive form. If there’s a short-term situation where there’s too much free thyroid hormone, the thyroid binding globulins bind the excess thyroid hormone so we don’t have symptoms of hyperthyroidism. If there is too little thyroid hormone being produced by the gland like for some reason (a short-term underproduction of T4 and T3), the thyroxine-binding globulin can release the T4 and the T3 that it’s carrying and that “free” thyroid hormone can now enter the cells and support metabolism.
- It Reduces Loss of Iodine: TBG reduces the loss of iodine, TBG helps preserve iodine, so we don’t lose as much.
- It Supports Uniform Distribution to Tissues: As soon as T4 and T3 is released from the thyroid gland, it’s in free form, once it binds to the TBG it’s now in bound form. When it’s bound, the thyroid hormone can then be transported around the body. When it gets to cells or tissues that need thyroid hormone it can be released and transported into the cells. If all thyroid hormone was in free form the cells closest to the thyroid gland would get saturated with thyroid hormone and the furthest away would get very little thyroid hormone. If thyroid hormone was all in free form we would probably have a lot more hyperthyroid symptoms because that thyroid hormone that’s free is able to immediately transport across cell membranes and be converted into T3. T3 that’s being released is active right away. We don’t want tons of free floating thyroid hormone circulating in the serum, we have it bound to these carrier proteins to protect us and it is released from TBG as it is needed under normal healthy situations.
- It Allows for Targeted Delivery: TBG is modifiable and this allows for a targeted delivery system. The cells of the body can modify the thyroid binding globulin and change the confirmation of it to either allow thyroid hormones to bind or for thyroid hormones to come off. This way the cells and what’s happening at the cellular level can really control the amount of thyroid hormone that’s being released, becoming free, and be transported into the cells.
THINGS THAT COMPETE FOR TBG OR BINDING OF THYROID HORMONES.
There’s a few things that can compete for thyroxine-binding globulin or decrease the binding of thyroid hormones; Dilantin, Salicylates (component in aspirin), and Human Leukocyte Elastase (HLE). When there’s inflammation, white blood cells can release something called human leukocyte elastase which can inhibit the binding of thyroid hormones to TBG. It changes the conformation (shape) of TBG so the thyroid hormones can’t bind and this allows for increased levels of free T4 and T3.
Severe illness will decrease the amount of circulating TBG. Therefore, if there’s decreased levels of these transport proteins, then there’s less availability for the free hormones to bind to these carrier molecules. We’ll have increased levels of free T4 and free T3 and that may show up as increased free T4 or free T3 in the serum or it could show up as increased hyperthyroid symptoms.
If there’s inflammatory mechanisms going on that are causing increased free T4 and free T3, those same inflammatory mechanisms may also decrease the transport of free T4 and free T3 into the peripheral tissues, so we probably won’t get those hyperthyroid symptoms but we may see elevated levels of free T4 and free T3. A doctor may say, hey you’re doing great because you have plenty of that free thyroid hormone in your serum. But if we see high free T3, high free T4 and there’s inflammatory situations it’s probably because our thyroid binding globulin levels have decreased.
Excess estrogen, whether it’s caused by an estrogen producing tumor, an estrogen producing mole, hormone replacement therapy or because of birth control therapy, or GI infections (bacteria can increase production of something called beta Glucuronidase in the gut, which kind of unwraps some of these Estrogens that are supposed to be detoxified and cleared through the stool, these b-glucuronidase enzymes unwrap those estrogens, the estrogens can recycle back into the system and those elevated Estrogens can increase the amount of TBG). If you have increased TBG, the thyroid hormones T4 and T3 will bind to the TBG and then we will have less free thyroid hormone floating around the body.
Why is that important? Because only free T4 and free T3 is available to get into the tissues, so if we have Estrogen overload (excess of amounts of estrogen), and increased thyroid binding globulins, then we have less free thyroid hormone able to get into the cells to stimulate our metabolism. You could have increased hypothyroid symptoms and low free T4 and low free T3 and yet our total T4 and total T3 could be totally normal.
Androgenic hormones will decrease thyroid binding globulins. Androgens like testosterone work opposite of the Estrogens. If you have increased androgens or anabolic steroids, you will have lower levels of thyroid binding globulin and therefore will have more free hormones, so that could increase metabolism.
About a third of our thyroxine-binding globulin is usually saturated with T4 and T3, so that leaves a lot of room or cushion for more T4 and T3 to be bound to these proteins. At any point in time, if there’s an excessive amount of T4 or T3 there is plenty of room for the thyroid binding globulin to pick up that excess so we don’t have too much free hormone floating around the system.
If the thyroid binding globulins are saturated then we can start to see elevated levels of free hormone build up. Typically, if we look at lab work, thyroxine-binding globulin isn’t often tested. The typical range they look at on lab reports is about 1.1 to 2.1 milligrams per deciliter. I wouldn’t worry about that too much. Just know that it isn’t often run. Some docs will run it, a lot of docs will not. In conventional medicine, usually it’s only TSH and T4 that are run. But, you may see it on your lab report, and if you do, just be aware those are the ranges.
Many times, docs will run a different test which gives us a value of how saturated the thyroxine-binding globulins are and that’s a test called resin T3 uptake. The resin T3 uptake is essentially a way to figure out how saturated the thyroxine-binding globulin are. That’s probably information for another post.
So, little wrap up here.
- There is something called thyroxine-binding globulin, it is the major transport protein for thyroid hormones around the body.
- TBG is not associated with Hashimoto’s disease, in the fact that thyroglobulin antibodies are not produced against TBG.
- Thyroglobulin antibodies are produced against thyroglobulin which is the precursor of T4 and T3 in the thyroid gland.
- When you have thyroglobulin antibodies, you’re not damaging the transport molecules, you’re seeing damage to the thyroid gland.
I think that wraps it up for today, what I’ll do is in another Thyroid Thursday I will explain thyroxine-binding globulin and resin T3 uptake and help you understand what the lab values mean so that you can be a little bit more familiar with it. This is plenty for one Thyroid Thursday post.
If you have any questions, you can email me directly at my office at Chronic Condition Recovery Center or you can reach out to me through the www.thyroidproblemsdoctor.com website.
