Thyroxine-binding globulin

Thyroxine-binding globulin (TBG) is a globulin that binds thyroid hormones in circulation. It is one of the three main transport proteins responsible for carrying the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the bloodstream. Among these, TBG has the highest affinity for T4 and T3 but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in the blood. It is produced in the liver and is a 54-kDa protein that, like other thyroid-binding proteins, plays a critical role in regulating the bioavailability of thyroid hormones and thus, indirectly, the metabolism.

Function

TBG's primary function is to transport thyroxine (T4) and triiodothyronine (T3) in the bloodstream. By binding these hormones, TBG helps maintain their solubility, prolongs their half-life, and regulates their access to tissues. The binding of thyroid hormones to TBG is reversible, allowing for the release of T4 and T3 when needed by the body's tissues. The equilibrium between bound and free thyroid hormones is crucial for the normal functioning of various physiological processes.

Clinical Significance

Alterations in TBG levels can affect the total serum concentrations of thyroid hormones, which can lead to misinterpretation of thyroid function tests if not properly accounted for. Elevated TBG levels can be seen in pregnancy, hepatitis, and in those taking estrogen-containing medications. Conversely, lower TBG levels can be observed in individuals with genetic mutations leading to TBG deficiency, severe illness, malnutrition, or those taking androgens or steroids.

1. 1. 1. Hyperthyroxinemia

Increased levels of TBG can lead to a condition known as hyperthyroxinemia, where there is an elevated concentration of total T4 and T3, but the free (biologically active) hormone levels remain normal. This condition is often asymptomatic and does not require treatment, but it is important to differentiate it from hyperthyroidism, where the levels of free thyroid hormones are elevated.

1. 1. 1. TBG Deficiency

TBG deficiency is a genetic condition that can lead to reduced levels of total T4 and T3, but with normal levels of free hormones. This condition is usually asymptomatic and does not affect thyroid hormone function in the body. However, it can lead to misinterpretation of thyroid function tests if not properly recognized.

Genetics

The gene for TBG is located on the X chromosome (Xq22.2). Mutations in this gene can lead to either an increase or decrease in TBG levels. TBG deficiency is inherited in an X-linked manner, meaning that males are more frequently and severely affected than females.

Testing

TBG levels can be measured directly in the serum to help interpret thyroid function tests, especially in cases where alterations in TBG levels are suspected. This measurement, combined with tests for free T4, free T3, and TSH, can provide a comprehensive overview of thyroid function and its regulation.

See Also

• Thyroid hormone
• Thyroid function tests
• Hyperthyroidism
• Hypothyroidism