Total Triiodothyronine

Triiodothyronine, or T3, is the active thyroid hormone in the body and a potent regulator of metabolic processes.  T3 plays a pivotal role in modulating metabolism, energy production, and body temperature regulation.  As a metabolic regulator, T3 has important roles in essentially every nucleated cell of the human body.

Within this complex hormonal interplay, the emergence of reverse T3, an inactive form of T3, adds a layer of clinical complexity. Understanding the balance between T3 and reverse T3 is vital, especially when considering cases where TSH may be low while T3 and T4 levels remain normal, shedding light on potential underlying health concerns. 

Exploring the nuances of T3 levels and associated clinical implications within the contact of a comprehensive thyroid assessment is imperative for holistic thyroid health management.

T3 Definition and Function

What is T3?

Triiodothyronine (T3) is a crucial thyroid hormone synthesized through the conversion of thyroxine (T4). While some T3 is made in the thyroid gland, the majority of circulating T3 comes from peripheral conversion of T4 to T3 outside of the thyroid gland, especially in the liver, kidneys, and brain, along with other organs that receive high blood flow.   [3., 21.]

Thyroid hormone consists of the thyroglobulin molecule with a specific number of iodine atoms attached: T4 contains 4 iodine atoms, while T3 contains 3 iodine atoms in a specific placement.  Reverse T3 also contains 3 iodine atoms, but in a different placement that renders the hormone reverse T3 nonfunctional.  

T4 is converted to T3 by the deiodinase family of enzymes.  Type 1 deiodinase enzymes are highly active in the liver and kidneys; type 2 deiodinase enzymes are active in muscle and in the glial cells of the brain.  A third type of deiodinase enzyme converts T4 to reverse T3, the inactive form of T3.  

T3 exists in two primary forms: free T3 (FT3), which circulates in the bloodstream and exerts direct biological effects, and bound T3, which attaches to carrier proteins and serves as a reservoir of inactive hormone. 

Function of T3: What Does T3 Do?

Triiodothyronine (T3) is a crucial thyroid hormone that plays a central role in regulating metabolism and maintaining overall physiological function in humans. It exerts its effects by binding to thyroid hormone receptors located in various tissues throughout the body, including the liver, muscles, and adipose tissue.

By doing so, T3 influences the expression of genes involved in energy metabolism, protein synthesis, and carbohydrate and lipid metabolism. 

Specific areas of function include:  [5., 16., 22.]

Cardiovascular system: T3 enhances cardiac output, stroke volume, and heart rate by augmenting myocardial contraction force and speed and promoting vasodilation in key tissues, leading to decreased peripheral vascular resistance and increased blood volume. 

Metabolism: T3 stimulates basal metabolic rate, heat production, and oxygen consumption by activating mitochondrial uncoupling proteins, which increase glucose and fatty acid uptake and oxidation to enhance thermogenesis. 

Respiratory system: T3 also regulates respiratory rate and minute ventilation to ensure adequate oxygen delivery to tissues.  Additionally, T3 stimulates erythropoiesis and hemoglobin production, which are essential processes that result in tissue oxygenation.   

Bones: T3 is essential for bone health throughout the lifespan.  Specifically, T3 stimulates fetal bone growth, and bone growth and remodeling in children and adults.

Nervous system: T3 activates the nervous system by heightening alertness and responsiveness to external stimuli. Additionally, it stimulates the peripheral nervous system to enhance peripheral reflexes, gastrointestinal tone, and motility.

Kidney function: T3 influences renal function by enhancing renal blood flow and glomerular filtration rate, affecting the clearance of various substances, including medications. 

Fetal development: in addition to supporting proper fetal bone growth and development, thyroid hormone is also essential for proper fetal development in general, particularly neural development.  

What is Reverse T3?

Reverse T3 (rT3) is an inactive form of the thyroid hormone T3, derived from the removal of an iodine atom from the T4 molecule.  It is structurally similar to T3, except that the deiodination process happens to an iodine atom at a different position than that of T3.  

Unlike the biologically active triiodothyronine (T3), reverse T3 lacks significant thyroid hormone activity and does not effectively bind to thyroid hormone receptors. Instead, it is often considered a competitive inhibitor, potentially interfering with T3 action. 

Reverse T3 is primarily produced in situations of physiological stress or illness, serving as a protective mechanism to downregulate metabolism and conserve energy during periods of decreased metabolic demand. Factors such as starvation, chronic illness, inflammation, or intense physical stress can trigger the conversion of T4 to reverse T3, diverting thyroid hormone metabolism towards this inactive form.

Testing for T3 Hormone

What is the T3 Blood Test?

The T3 blood test measures the levels of triiodothyronine, a thyroid hormone, in the bloodstream. It is used to assess thyroid function and diagnose conditions such as hyperthyroidism or hypothyroidism.

There are two versions of the T3 blood test: total T3, and free T3.

Total T3 measures the amount of total T3 in the blood, which is available in free and bound forms.  Free T3 only measures the level of free, or bioavailable, T3 in the blood.

T3 Blood Test Procedure

The T3 blood test measures the levels of triiodothyronine, or T3, in the bloodstream. It requires a blood sample drawn from a vein, typically in the arm.  It is often performed alongside other thyroid function tests like TSH and T4 to provide a comprehensive evaluation of thyroid health.

The American Thyroid Association recommends running thyroid blood tests before taking thyroid medication.  [7.]

Some lab companies offer a blood spot version of this test, which can be done at home.  The sample is then mailed into the lab.

Clinical Significance of T3 Levels

Interpreting T3 Levels with Low TSH and Normal T4

When T3 levels are high while TSH is low and T4 remains normal, it could indicate a condition known as hyperthyroidism. In this scenario, the thyroid gland is overactive, producing excessive amounts of thyroid hormones, including T3. 

This situation may lead to symptoms such as weight loss, rapid heartbeat, anxiety, and heat intolerance. Further evaluation by a healthcare provider is essential to determine the underlying cause and appropriate management.

Understanding Reverse T3

Reverse T3, or rT3, is an inactive form of thyroid hormone that is produced in small amounts in the body. It is created when T4 is converted into an inactive form instead of being converted into the active form of T3. 

High levels of reverse T3 can occur in situations of illness, stress, with certain medications, or when the body is trying to conserve energy.  Some individuals may also have a genetic tendency toward reverse T3 production.  [8.]

Elevated reverse T3 levels are often associated with non-thyroidal illness syndrome.  [20.]  Elevated reverse T3 may indicate a state of thyroid hormone imbalance, or an extrathyroidal medical condition and may require further investigation to identify and address the underlying cause.  [8.]

What is Free T3?

In contrast to reverse T3, which is always inactive, free T3 is active and bioavailable.  Bound T3 acts as a storage form of T3, and becomes active and bioavailable as soon as it’s liberated from its carrier protein in the bloodstream.  

The three most common carrier proteins for thyroid hormone in the bloodstream are thyroxine binding protein, transthyretin, and albumin.  [13.]

Free T3 is clinically important because all of the actions of thyroid hormones occur from the interactions between free T3 and the thyroid hormone receptor, located at the nucleus of most cells.  When free T3 binds to its receptor, it alters gene expression inside the cell.  

Free T3 levels are affected by the rate of conversion from T4 to T3, the amount of carrier proteins present, and the rate of breakdown of T3.  [13., 17.]

Managing T3 Levels

Taking T3 for Weight Loss

Taking T3 hormone for weight loss is a practice that has gained attention in some circles, particularly among individuals seeking rapid weight loss.  [11.]  As discussed, T3 plays a crucial role in regulating metabolism and energy expenditure in the body. 

Some proponents of T3 supplementation for weight loss believe that increasing T3 levels can boost metabolism, leading to greater calorie burning and subsequent weight loss. However, the use of T3 for weight loss is controversial and not without risks. 

Inappropriate use or excessive doses of T3 can lead to hyperthyroidism, characterized by symptoms such as rapid heartbeat, tremors, sweating, and anxiety. Moreover, T3 supplementation should only be considered under the guidance of a healthcare professional, as it requires careful monitoring to avoid potential adverse effects and ensure its safe and effective use for weight management purposes.

Natural Strategies to Address High Reverse T3 or Low Free T3

Nutrition for Thyroid Health

Selenium-rich Foods: increase consumption of selenium-rich foods like Brazil nuts, eggs, and sunflower seeds, as selenium plays a role in thyroid hormone metabolism.

Iodine-rich Foods: incorporate a serving of iodine-rich foods such as seaweed, fish, and shellfish as iodine is essential for thyroid hormone synthesis.

Zinc-rich Foods: consume foods high in zinc, such as oysters, beef, and pumpkin seeds, as zinc helps regulate thyroid function.  [4.]

Goitrogen Foods: limit consumption of raw cruciferous vegetables such as broccoli, cabbage, and cauliflower, as they contain compounds that can interfere with thyroid hormone synthesis when consumed in large amounts.  It is generally recommended to wash and cook these foods to reduce their goitrogenic tendency.

Avoid Processed Foods: minimize intake of processed and refined foods, including packaged snacks, sugary beverages, and foods high in artificial additives and preservatives, as they can contribute to inflammation and disrupt thyroid function.  [23.]

Lifestyle Adjustments for Thyroid Health

Stress reduction: manage stress levels through techniques like meditation, yoga, or deep breathing exercises, as stress can impact thyroid hormone levels. [9.]

Get enough sleep: ensure adequate sleep hygiene and aim for sufficient restorative sleep each night, as sleep deprivation can increase reverse T3 production and affect thyroid function.  [14., 18.]

Exercise: engage in regular physical activity, including both aerobic and strength-training exercises, to support overall metabolic health.  [6.]

Herbal and Supplement Support for Thyroid Health

Herbal adaptogens: consider supplementing with adaptogenic herbs like ashwagandha and rhodiola, which may help support thyroid function and reduce stress.  [10., 19.]  

Vitamin D: low vitamin D has been associated with hypothyroidism and with autoimmune thyroiditis.  Individuals with hypothyroidism may benefit from having vitamin D levels assessed, and supplementing appropriately if low.  [1., 12.]

Consult with a healthcare professional before starting any new supplements, as individual needs may vary, and certain supplements may interact with medications or underlying health conditions.