T3 Uptake

Thyroid function is essential in regulating metabolism, energy levels, and overall well-being, making it imperative to understand the various biomarkers used to assess thyroid health. One such biomarker, T3 uptake or T3 resin uptake (T3RU), offers valuable insights into thyroid function and can aid clinicians in diagnosing and managing thyroid disorders. 

This article explores the intricacies of T3 uptake by reviewing its definition, clinical significance, and interpretation in the context of thyroid function testing. 

By examining the science behind T3 uptake and its role in thyroid panels, we aim to provide readers with a deeper understanding of this important thyroid marker and its implications for overall health and wellness.

What is T3 Uptake?

Definition of T3 Uptake

T3 uptake, also known as T3 resin uptake (T3RU), describes the binding capacity of thyroid hormone-binding proteins in the bloodstream, primarily thyroxine-binding globulin (TBG). It assesses the availability of binding sites for thyroid hormones, particularly thyroxine (T4), within the blood plasma. 

Despite its name, T3 uptake does not directly measure the uptake of T3 by cells but instead evaluates the extent to which thyroid-binding proteins are saturated with thyroid hormones.  

It has been used historically to understand whether a high or low T4 value is actually due to an alteration of T4 production vs. an alteration in availability of TBG.  

Clinical Significance of T3 Uptake

The clinical significance of T3 uptake lies in its ability to provide insights into thyroid function and hormone levels. While T3 uptake itself does not directly measure thyroid hormone concentrations, it indirectly reflects changes in thyroid hormone-binding protein levels. 

Low T3 uptake may suggest low levels of free thyroid hormones, indicating hypothyroidism or conditions affecting thyroid-binding proteins, while high T3 uptake may indicate elevated free thyroid hormones, suggesting hyperthyroidism.

A simple way to remember the clinical utility of T3 uptake is to remember that it has a direct relationship with the concentration of thyroxine, or T4, in the blood and an inverse relationship with the concentration of binding proteins, particularly thyroxine binding globulin, in the blood.  

In overt hyperthyroidism, there is more T4 in the bloodstream so fewer binding sites on TBG will be available.  This correlates with a higher T3 uptake level.  

In overt hypothyroidism, or in situations of increased concentration of TBG in the blood, there will be less T4 available (hypothyroidism) or more binding sites on TBG will be available (in certain clinical settings), so the T3 uptake will be lower.  

It is important to understand that variations in availability of thyroid binding proteins can cause a clinical appearance of hyper- or hypothyroidism in the setting of normal thyroid function.  Certain medications or hormone therapies can increase or decrease the availability of TBG, and some patients may have a TBG deficiency (often diagnosed in newborns).  [3.]

With the increasing availability of total and free T3 and T4 testing and binding protein assays, this test is used less frequently than it was historically.  

A TBG deficiency is clinically significant because TBG is essential to maintain a stable pool of thyroid hormones in the bloodstream. Without TBG, research suggests that existing thyroid hormone levels would be depleted within a short period.  [14.]

However, with TBG present, there is only a minimal decrease in thyroxine (T4) and triiodothyronine (T3) levels, demonstrating its role in preventing abrupt fluctuations in thyroid hormone levels. 

Conversely, a decrease in TBG levels leads to an increase in free T4, which then inhibits thyroid-stimulating hormone (TSH) production. Consequently, total T4 production decreases, so serum free T4 levels return to normal.  [6.]

What is the Science Behind the T3 Uptake Test?

The T3RU, or T3 Uptake, serves as an indirect assessment of thyroxine-binding globulin (TBG) binding capacity. 

In this test, a T3 resin binder is mixed with a patient's serum, along with a small amount of radioactive iodine-labeled T3 (125I-T3). This is then incubated for a period of time to allow the  125I-T3 to distribute between the resin binder and serum binding sites available in the patient’s blood. 

After incubation the serum is removed, and the remaining 125I-T3 activity on the resin binder is measured. The percentage of 125I-T3 retained on the resin binder, relative to the total 125I-T3 added, multiplied by 100, defines the T3RU. 

Normal T3RU values typically range between 25 and 50%, although many labs report normal values between 25-39% for adults.  [1., 4.]

Factors Affecting T3 Uptake

Medical Conditions

• Thyroid disorders such as hyperthyroidism or hypothyroidism can impact T3 uptake levels.
• Liver disease, including cirrhosis, may affect the synthesis and metabolism of thyroid-binding proteins, thereby influencing T3 uptake.
• Renal dysfunction such as nephrotic syndrome can alter the clearance of thyroid hormones with pronounced proteinuria, potentially affecting T3 uptake.
• Pregnancy and estrogen therapy can lead to increases in thyroid-binding proteins, decreasing T3 uptake levels.
• Genetic conditions affecting thyroid hormone binding proteins may impact T3 uptake, as seen in TBG deficiency of the newborn.  [3.]

Medications and Supplements

Drugs that Increase TBG and Decrease T3 Uptake [11.]

• Estrogen-containing medications such as oral contraceptives or oral hormone replacement therapy (not transdermal) may increase thyroid-binding protein concentrations, thereby reducing T3 uptake.
• raloxifene, tamoxifen, mitotane, fluorouracil, methadone and heroin and other opiates can all increase TBG and therefore decrease T3 uptake

Drugs that Decrease TBG and Increase T3 Uptake [11., 16.]

• Glucocorticoids can decrease TBG synthesis 
• Androgen therapy can decrease TBG synthesis 
• Nicotinic acid can decrease TBG synthesis
• Furosemide (especially with doses >80 mg/day and when given intravenously), aspirin, nonsteroidal anti-inflammatory agents, phenytoin can all compete with thyroxine for available TBG binding sites, causing an increase in T3 uptake
• Heparin also competes with thyroxine for thyroid hormone binding sites, causing an increase in T3 uptake.  This is important to note because of the widespread use of low molecular weight heparin thromboprophylaxis 

T3 Uptake Test Procedure and Preparation

Test Procedure

The T3 uptake test involves a simple blood draw, where a healthcare professional collects a sample of venous blood from the patient's arm.   After the blood sample is collected, it is processed in a laboratory where the T3 uptake is measured using specialized assays. 

Test Preparation

Patients may be advised to inform their healthcare provider about any medications, supplements, or medical conditions they have, as certain factors can influence T3 uptake levels.  Biotin is a commonly-used supplement that is well-known to alter thyroid function studies.  [9.]

Patients usually do not need to fast before the test, and there are no dietary restrictions. 

However, it is essential to follow any instructions provided by the healthcare provider regarding medication use or fasting if indicated.

Interpretation of T3 Uptake Results

Normal Reference Range

Falling within the normal range for T3 uptake typically indicates adequate binding capacity of thyroid-binding proteins and balanced thyroid hormone levels. 

In a healthy individual, the T3 uptake value reflects the proportion of available binding sites on thyroid-binding proteins occupied by thyroid hormones. Normal T3 uptake values vary between laboratories but generally fall between 25% and 50%, depending on the assay methodology and reference ranges used.  

Common normal findings fall between the following ranges: [1., 2., 15.]

Male

0-11 months: 23-34%

1-3 years: 24-35%

4-6 years: 24-34%

7-11 years: 24-33%

12-15 years: 25-37%

16-18 years: 24-38%

>18 years: 24-39%

Female

0-11 months: 23-36%

1-3 years: 24-36%

4-6 years: 24-35%

7-11 years: 22-35%

12-15 years: 23-37%

16-18 years: 23-35%

>18 years: 24-39%

Because different labs may report different findings based on their results over time, it is important to consult your lab company for their reference ranges.  

Low T3 Uptake

A low T3 uptake indicates an excess of free thyroid hormones causing saturation of thyroid-binding proteins, leading to reduced binding capacity. 

It is essential to determine the cause of low T3 uptake as a primary thyroid illness, an extrathyroidal illness, or the side effect of certain drugs or medications.  

High T3 Uptake 

Elevated T3 uptake levels indicate decreased thyroid hormone levels leading to increased binding capacity of thyroid-binding proteins. 

It is essential to determine the cause of high T3 uptake as a primary thyroid illness, and extrathyroidal illness, or the side effect of certain drugs or medications.  

How to Increase T3 Uptake

Thyroid Hormone Replacement Therapy: Adjusting thyroid hormone medications such as levothyroxine to achieve optimal thyroid hormone levels may influence T3 uptake.

Estrogen Therapy: Estrogen-containing medications like oral contraceptives or oral hormone replacement therapy may increase thyroid-binding protein concentrations, potentially decreasing T3 uptake  Pregnant women should have their thyroid function monitored throughout pregnancy and postpartum.

Lifestyle Modifications: Regular physical exercise, adequate sleep, and stress management techniques can help regulate thyroid function and hormone levels, potentially impacting T3 uptake.  [8., 9., 10.]

Nutritional Support: Consuming a balanced diet rich in nutrients like protein, vitamins, and minerals supports optimal thyroid function, potentially affecting T3 uptake.  [5.]

Avoiding Stimulants: Limiting consumption of stimulants like caffeine and nicotine may help regulate thyroid hormone levels and prevent excessive fluctuations that could influence T3 uptake.  [7., 12., 17.]

Monitoring Medications: Being mindful of medications that can affect thyroid function and TBG availability such as glucocorticoids or heparin and working with healthcare providers to adjust dosages or find alternatives if necessary can impact T3 uptake.

Addressing Underlying Conditions: Treating underlying medical conditions that may affect thyroid function, such as liver or kidney disease, can help normalize T3 uptake levels.

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