What is Thyroxine-Binding Globulin Deficiency?
Thyroxine-binding globulin (TBG) is one of three major proteins that carry thyroid hormones to the body parts that need them. Thyroid hormones are important in regulating your body’s metabolism or how your body uses energy. The other two proteins that help transport thyroid hormones around the body include transthyretin and human serum albumin. Even though human serum albumin is more in quantity in the body fluids, TBG likes to connect with a specific thyroid hormone called thyroxine (T4) the most.
A change in the functioning or quantity of TBG can alter the total amount of T4 in the body fluids, but it doesn’t affect the active T4 that is ready to work. That’s why a lack of TBG generally doesn’t lead to the metabolic problems we usually see when thyroid hormone levels are out of balance. However, it can confuse the results of thyroid hormone tests, leading to possible wrong treatments.
This simplified information intends to give you a clear understanding about the cause, diagnosis and handling of a condition where there is a shortage in thyroxine-binding globulin.
What Causes Thyroxine-Binding Globulin Deficiency?
Thyroxine-binding globulin (TBG) is a protein that stops certain enzymes from working too much and it’s made in the liver. It’s part of a protein family called SERPINA7. The gene responsible for making TBG is on a part of the X chromosome. Because of where the gene for TBG is, when it’s passed down in families, it often follows a pattern linked to the X chromosome. So far, scientists have found about 27 mutations, or changes, in this gene that can cause a complete lack of TBG in people. These mutations can come from a single building block of DNA being swapped out or by a ‘misreading’ of the DNA sequence.
People can also have a lack of TBG due to other reasons apart from genetics. These are called acquired forms of TBG deficiency. For example, in people with an overactive thyroid (hyperthyroidism), TBG is used up faster than it can be made. In people with serious illnesses, a substance called interleukin-6 can affect TBG levels. Also, levels of TBG can change if there are changes in sex hormones. For example, estrogen can increase TBG levels, while androgens, another type of sex hormone, can lower TBG levels.
Risk Factors and Frequency for Thyroxine-Binding Globulin Deficiency
Thyroxine-binding globulin (TBG) deficiency is a condition that can be inherited. The most common type of this inherited condition is the partial TBG deficiency, affecting 1 in 4,000 newborns. A more severe form, complete TBG deficiency, affects 1 in 15,000 male newborns. There is no evidence to suggest that any specific race is more prone to TBG deficiency.
Signs and Symptoms of Thyroxine-Binding Globulin Deficiency
TBG deficiency, which can either be inherited or acquired, does not have specific signs or symptoms. However, it can be suspected in people with a strong family history of the condition. If you’ve acquired TBG deficiency, you might experience symptoms that relate to a severe underlying illness like liver disease or conditions that cause loss of protein through your kidneys. It could also be associated with the use of drugs like anabolic steroids or androgens.
In both inherited and acquired forms of TBG deficiency, physical examinations typically show no unusual findings. Any deviations are likely due to another underlying disease. A scenario could be a woman with total TBG deficiency appearing with characteristics of Turner syndrome, such as a short stature and a webbed neck.
Testing for Thyroxine-Binding Globulin Deficiency
If a newborn baby has inherited a condition called thyroid binding globulin deficiency, it is usually detected during a check for a disorder known as congenital hypothyroidism. The test for newborns usually examines either TSH (thyroid-stimulating hormone) or total T4 (thyroxine), or sometimes both. If the level of total T4 falls below a certain limit, the result is deemed positive, meaning there might be a problem.
To be sure of the diagnosis, additional tests are carried out, which measure levels of TBG (thyroid-binding globulin), free T4, and TSH. These tests help to confirm or rule out the diagnosis of congenital hypothyroidism or TBG deficiency.
It has been discovered that TBG can be found in a fetus’s blood as early as 12 weeks into pregnancy. The level of TBG is about 1.5 times higher than in an adult until adolescence when it starts to drop. On the other hand, the normal level of TBG in an adult male is between 1.1 to 2.1 mg/dl.
Studies have shown that boys with this condition can exhibit mild to severe variations in their thyroid hormone levels. Girls, on the other hand, are rarely found to have any significant hormonal changes except in cases where they have Turner syndrome, a condition that affects girls and women.
In a male with a fully developed TBG deficiency, the level of TBG is found to go below 5 mg/L, which is quite low. In partially affected females, the level of TBG is usually close to normal. TBG deficiency can also be discovered by accident during medical examinations. In such cases, if other potential causes of TBG deficiency are ruled out, there’s a high possibility that the patient has inherited the condition, in which case a genetic test might be recommended to confirm this.
Treatment Options for Thyroxine-Binding Globulin Deficiency
If you have a condition that leads to acquired TBG deficiency, managing that condition could help improve your TBG levels. TBG or Thyroxine-binding globulin is a protein that carries the thyroid hormone in your blood. However, the hormone replacement medication called l-thyroxine may not be necessary. This is because even though TBG levels might change, the amount of active free T4, another thyroid hormone, remains the same in your body.
What else can Thyroxine-Binding Globulin Deficiency be?
When a patient has symptoms of TBG deficiency, there are similar conditions that the doctor will need to rule out as part of the diagnosis process. These conditions include central hypothyroidism and euthyroid sick syndrome. Both of these can show similar signs in blood tests, such as low levels of FT4, Total T4, and possibly even TSH, a hormone that usually regulates thyroid function.
Central hypothyroidism can either be present from birth or develop later in life. There’s also a situation where a patient is seriously ill from a non-thyroid related condition, but their thyroid tests comes back similar to those for TBG deficiency. In these cases, they’ll typically show high reverse T3 levels because their body isn’t clearing this hormone as efficiently. Once the underlying illness resolves, these thyroid anomalies usually go away.
What to expect with Thyroxine-Binding Globulin Deficiency
TBG deficiency is nothing to worry about – it’s a harmless condition and the outlook is positive. People who are born with this condition only need assurance. They should also receive information about what this condition means and what to expect.
Possible Complications When Diagnosed with Thyroxine-Binding Globulin Deficiency
Problems can arise from misunderstanding total T4 levels. Therefore, side effects from incorrect treatment and signs of overactive thyroid can happen as a result of improper use of levothyroxine.
Possible Complications:
- Misinterpretation of total T4 levels
- Incorrect treatment with levothyroxine
- Manifestations of overactive thyroid
