The T3 Uptake (T3U) test is a component of a blood panel used to evaluate thyroid gland function. Despite its name, the test does not directly measure the concentration of triiodothyronine (T3). Instead, the T3U test provides an indirect assessment of the availability of transport proteins that carry thyroid hormones. This metric is most informative when considered alongside other results, such as the total level of thyroxine (T4).
The Transport System: Understanding Binding Globulins
Thyroid hormones (T4 and T3) are not freely dissolved in the blood plasma. Over 99% of these hormones are bound to specialized carrier proteins, primarily Thyroxine-Binding Globulin (TBG), which ensures their solubility and regulates delivery to target tissues. These bound hormones are largely inactive, acting as a reservoir.
Only the small, unbound fraction, known as “free” hormone, is biologically active and regulates metabolism. The amount of free hormone is controlled by the balance between the total hormone produced and the number of available binding sites on the transport proteins. These sites become more or less saturated depending on the concentration of T4 and T3 in the blood.
The T3 Uptake Mechanism: Measuring Unoccupied Binding Sites
The T3 Uptake test measures the saturation level of thyroid hormone transport proteins, indirectly assessing the number of unoccupied binding sites on proteins like TBG. The laboratory procedure involves adding a known quantity of radioactively labeled T3 (the tracer) to the patient’s blood serum.
The tracer T3 competes with the patient’s existing thyroid hormones for the available binding sites. After incubation, a secondary material is introduced to bind the remaining unbound tracer. The amount of radioactive T3 that binds to this secondary material is measured as the T3 uptake value.
A high T3U value indicates that a large amount of tracer bound to the secondary material. This occurs when the patient’s transport proteins are highly saturated by endogenous hormones, leaving few sites for the tracer to bind to them. Conversely, a low T3U means the patient’s proteins were undersaturated, allowing the tracer to bind readily to them instead of the secondary material. Therefore, the T3U result is inversely related to the degree of saturation of the transport proteins in the blood.
Interpreting High and Low Results
An abnormal T3 Uptake result most frequently reflects a change in the quantity of the transport protein, TBG, or a change in the amount of thyroid hormone occupying its binding sites.
High T3U Results
A high T3U value suggests a state where the transport proteins are highly saturated. This can occur in hyperthyroidism, where the gland is overactive and circulating T4 levels are very high, occupying most of the binding sites. It can also signify a true decrease in the total amount of circulating TBG, which lowers the number of binding sites overall.
TBG levels can be lowered by non-thyroid-related conditions, leading to a high T3U even if the thyroid gland is functioning normally. For example, severe liver disease or nephrotic syndrome can reduce the production or increase the loss of TBG, respectively. Certain medications, such as androgens and high-dose corticosteroids, can also suppress TBG synthesis.
Low T3U Results
A low T3U value suggests the opposite: a state where the transport proteins are undersaturated. This typically occurs in hypothyroidism, where a low output of T4 leaves many protein binding sites unoccupied, allowing the tracer T3 to bind more readily to the patient’s proteins. However, a low T3U can also be caused by an increase in the total amount of circulating TBG.
The TBG concentration is commonly elevated due to the presence of estrogen, which is seen in pregnancy or in individuals taking oral contraceptives or estrogen replacement therapy. This increase in the number of binding sites leads to a high number of tracer T3 molecules binding to the patient’s proteins, resulting in a low uptake reading. In these scenarios, the low T3U is a reflection of altered protein levels, not necessarily thyroid dysfunction.
How T3 Uptake is Used Clinically
The T3 Uptake result is seldom used as a standalone measurement for diagnosing thyroid conditions. Its primary clinical utility lies in its combination with the total T4 concentration to generate the calculated Free Thyroxine Index (FTI), sometimes referred to as the T7. The FTI is calculated by multiplying the Total T4 by the T3U ratio.
This calculated index corrects the total T4 measurement for the confounding effects of abnormal binding protein levels. Since Total T4 measures both the bound and free hormone, fluctuations in TBG can artificially inflate or deflate the Total T4 result. By incorporating the T3U, the FTI provides a more accurate, indirect estimate of the biologically active free T4 concentration, allowing clinicians to distinguish between a true thyroid hormone imbalance and an alteration in the hormone transport system.