In Part 1 of this series on hormone-binding globulins, I covered sex hormone binding globulin, how it influences estrogen and testosterone, and what to do when it’s high or low.

Today I’ll cover another crucial protein: thyroxine-binding globulin, TBG for short.  TBG binds to thyroid hormone and will affect thyroid hormone levels. It may be an important piece of your thyroid health picture. 

TBG binds to thyroid hormone and will affect thyroid hormone levels. It may be an important piece of your thyroid health picture.

Keep reading to learn more about:

• TBG and thyroid hormones
• High thyroid-binding globulin causes
• How to lower TBG levels

Let’s get started!

What is TBG (Thyroxine-Binding Globulin) and what is its Function?

TBG, like SHBG, is a protein produced in the liver. TBG binds to thyroid hormones to transport them through the bloodstream. It helps to manage levels of thyroid hormone and prevent fluctuations. 

Although it’s called thyroxine-binding globulin, it binds to thyroxine (T4) and triiodothyronine (T3). (Maybe it should be called thyroid-binding globulin!) When bound, thyroid hormones are not available to bind to cells and exert their effect. 

High levels of TBG mean lower levels of free thyroid hormones. High levels are seen in Hashimoto’s thyroiditis and pregnancy, as I’ll discuss below. 

Low TBG may be related to hyperthyroidism (elevated thyroid hormone or Graves’ disease), liver disease, and severe illness. With hyperthyroidism, there is an increased turnover rate of TBG. 

Other hormone systems influence TBG. Estrogen tends to increase TBG, while testosterone and other androgens tend to decrease it. TBG is a simple blood test that we can easily add to a thyroid panel. 

Thyroxine-Binding Globulin Binds to Thyroid Hormones

Let’s look at both thyroid hormones: T4 and T3. 

Thyroxine 

Thyroxine is the primary thyroid hormone produced in the thyroid gland. It’s called T4 because it contains four molecules of iodine attached to tyrosine. (Tyrosine is an amino acid we obtain from protein foods in the diet). The brain signals the thyroid to make T4 using an enzyme called thyroid peroxidase, or TPO. The signal is called TSH, or thyroid stimulating hormone. Most T4 travels through the blood bound to TBG, while the remaining free thyroxine is available to convert to T3. 

Triiodothyronine 

Triiodothyronine is the active thyroid hormone. It’s called T3 because it contains three iodine molecules. T4 must release an iodine molecule to become free triiodothyronine, where it can go on to bind to every cell in the body, increasing the metabolic rate and cellular function. A small amount of T3 is made in the thyroid, but most of it is activated in the liver and the gut, making both liver health and gut health necessary for triiodothyronine function. When T4 converts to T3, TBG transports T3 in the blood. 

Don’t worry if this biochemistry is hard to follow; the main point is that your thyroid makes T4, and it must convert to T3 to be active. Both T4 and T3 are transported by TBG, which helps moderate thyroid hormone levels. 

Elevated TBG Levels May Be Caused By:

Both elevated TBG and TBG deficiencies are possible based on various factors. When TBG levels are abnormal, they will influence the amount of total T4 in the serum but not necessarily the amount of free T4. Abnormal TBG levels contribute to improper diagnosis of thyroid conditions. 

Let’s explore some of the factors related to elevated TBG.  

Hypothyroidism

Hypothyroidism is a condition where thyroid hormone levels are low. Hashimoto’s thyroiditis is an autoimmune disease that causes hypothyroidism and loss of thyroid function. Hashimoto’s is the most common thyroid disorder, primarily affecting women. 

Interestingly, thyroid hormones (T4 and T3) help to regulate levels of thyroxine-binding globulin in the blood. Hypothyroidism increases TBG and the ability to bind up more thyroid hormones. 

Liver Disease

The liver manufactures TBG, so anything that impacts liver function may also impact the liver’s production of TBG.  For example, the estrogen in birth control pills increases the production of various liver proteins, including TBG and SHBG. TBG may be elevated in people with liver cancer, and TBG has less ability to bind to T4. Less binding is also seen in chronic liver disease. 

Pregnancy

Thyroid hormones significantly increase during pregnancy to support the growth and development of the fetus. Because of the increased estrogen levels during pregnancy (and likely other factors), TBG levels also increase. 

One study found that TBG levels in late pregnancy predictive of postpartum depression. 

A Functional Medicine Approach to Lowering TBG Levels

When TBG levels are out of range, either high or low, I want to understand why and uncover the root causes. I might anticipate higher levels, as in the case of pregnancy or Hashimoto’s disease. There may also be specific genetic polymorphisms that contribute. 

I also want to understand TBG’s role in overall thyroid health. There may be some cases where changes in TBG don’t influence active thyroid hormone or contribute to symptoms of hypo or hyperthyroidism. 

I always run a full thyroid panel to assess thyroid health. A full thyroid panel includes:

• TSH – thyroid stimulating hormone
• Free T4
• Free T3
• Total T4 (this includes T4 bound to TBG)
• Total T3 (this includes T3 bound to TBG)
• Thyroid antibodies to assess autoimmunity 

Functional medicine offers personalized solutions to address thyroid health. I always look at the whole person and take an integrative approach. If you are interested in learning more, please reach out. 

References

1. Chakravarthy, V., & Ejaz , S. (2022). Thyroxine-Binding Globulin Deficiency. In StatPearls. StatPearls Publishing.
2. Savu, L., Vranckx, R., Maya, M., Gripois, D., Blouquit, M. F., & Nunez, E. A. (1989). Thyroxine-binding globulin and thyroxine-binding prealbumin in hypothyroid and hyperthyroid developing rats. Biochimica et biophysica acta, 992(3), 379–384. 
3. Torre, F., Calogero, A. E., Condorelli, R. A., Cannarella, R., Aversa, A., & La Vignera, S. (2020). Effects of oral contraceptives on thyroid function and vice versa. Journal of endocrinological investigation, 43(9), 1181–1188. 
4. Kalk, W. J., Kew, M. C., Danilewitz, M. D., Jacks, F., van der Walt, L. A., & Levin, J. (1982). Thyroxine binding globulin and thyroid function tests in patients with hepatocellular carcinoma. Hepatology (Baltimore, Md.), 2(1), 72–76. 
5. Hutchinson, W. L., White, Y. S., Fagan, E. A., Johnson, P. J., & Williams, R. (1991). Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease. Hepatology (Baltimore, Md.), 14(1), 116–120. 
6. Krysiak, R., Okopień, B., Szkróbka, W., & Herman, Z. S. (2007). Choroby tarczycy w ciazy i po porodzie [Thyroid disorders in pregnancy and after delivery]. Przeglad lekarski, 64(3), 159–164.
7. Pedersen, C., Leserman, J., Garcia, N., Stansbury, M., Meltzer-Brody, S., & Johnson, J. (2016). Late pregnancy thyroid-binding globulin predicts perinatal depression. Psychoneuroendocrinology, 65, 84–93. 
   

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