Thyroid FT3, FT4 and TSH

What’s covered?

Free T3 is a subtype of free thyroid hormones. Thyroxine is produced in the thyroid gland and can be found in blood circulation in two forms: bound to thyroxin-binding globulin (TBG) or unbound to any binding protein, known as free T4 (FT4). Free T3 exists as an unbound form free T3 in either a plasma membrane-impermeable or membrane-permeable form. The plasma membrane impermeability of FT3 means that it has to enter cells by active transport through membrane receptor proteins. Thus, the amount of total FT3 depends on how much is both TBG bound and how much not. Normal serum concentration of FT3 ranges between 1.8 and 4 pg/ml (pico grams per milliliter). FT4 and unbound FT3 are typically between 6.5 to 21.7 pico grams per milliliter, with free T3 having a higher concentration than free thyroxine (FT4) in serum.

FT4 and FT3 are bound to a transport protein, known as thyroxine-binding globulin (TBG), which transports the hormones in circulation. However, because of its large size, it cannot pass through cell membranes and thus is not readily available for use by cells. As such, only the unbound hormone molecules can be utilized by cells. In addition to TBG, there are other proteins that bind T4 and T3 in circulation including transthyretin and albumin. Whereas both TBG and TBPA have high affinity for T4, they differ in their respective affinities for binding with free T3: while TBPA has a higher affinity than TBG, albumin has an even lower affinity than transthyretin.

Free T3 is the only active form of T3 hormone, the other being its inactive de-iodinated metabolite, known as reverse triiodothyronine (rT3). The amount of FT4 and FT3 by themselves do not have any effect on cellular metabolic activity. All hormones are proteins that relay messages to cells in order for them to perform specific functions throughout various parts of the body. However, since only a very small percentage is available at any given time (~0.1% free T4), a feedback system within the thyroid gland serves to regulate their concentrations through) the release of thyroid-stimulating hormone (TSH) from the pituitary gland.

Although FT3 is considered to be the main form that regulates metabolic activity, there are certain areas where free T4 is more active than free T3. These include: areas in the central nervous system and skeletal muscle, which also have a greater affinity for binding with TBG due to their high amounts of these receptors as compared to other tissues throughout the body. As such, most tissues exhibit a preference for receptor proteins possessing a higher affinity for binding with either both free T4 or free T3 hormone molecules. This phenomenon can cause an increase in cellular metabolism by activating protein kinases (), which are enzymes that catalyze various types of phosphorylation reactions. Protein phosphorylation is a process responsible for regulating numerous cellular events including gene expression, protein synthesis and metabolism, enzyme activity (including those involved in lipid metabolism), and cell division or cell survival. If you would like more details, visit our comprehensive guide to blood testing here.

In addition to its role in regulating metabolic activity through these mechanisms, free T3 is also known to activate the transcription of nuclear receptors that code for enzymes involved in cholesterol biosynthesis. This can lead to increases in serum concentrations of cholesterol and triglycerides. As such, decreased levels of FT3 can contribute to decreases in metabolic activity by inhibiting the production of these compounds as well as reducing their subsequent uptake into cells that require it for energy production. Although not confirmed by scientific research, there has been evidence suggesting that diminished levels may be associated with a higher risk of certain types of cancer (e.g., colorectal, breast, and lung).

As mentioned earlier, free T3 is the preferred form of the hormone in the central nervous system (CNS), and this is important to consider when it comes to the treatment of conditions related to weight loss or seizure control. This is because most anticonvulsant medications are thought to work by reducing energy demand within neurons. As such, these drugs require an efficient means for utilizing available energy from carbohydrates and fats that can be converted into ATP molecules (the source of cellular energy) through glycolysis and beta-oxidation, respectively. In order to have an impact on the amount of circulating free T3 in the blood, these anticonvulsant drugs utilize proteins with a higher affinity for binding such as TBG and transthyretin.

As mentioned earlier, free T3 is also thought to be involved in regulating the rate of gene transcription by activating transcription factors. Therefore, it can influence cell growth and division as well as cellular differentiation (i.e., changes in a cell's phenotype) through its interaction with monoamine neurotransmitters (such as norepinephrine). This mechanism has been associated with a number of neurodegenerative disorders including Alzheimer's disease (). Considering that this hormone is involved in maintaining metabolic activity throughout various tissues within the body (), its diminished levels have been linked to weight loss or decreased vitality over time, a condition known as euthyroid sick syndrome (). Furthermore, low levels of free T3 can also lead to decreased growth and development in children with the potential to result in their stunted growth. Because of these effects on metabolism and gene transcription, free T3 has been considered an important biomarker for assessing thyroid functioning and overall health status within patients.

In summary, free T3 is a critical hormone that influences metabolic activity throughout the body. The activation of protein kinases and transcription factors are just some of the mechanisms by which it can influence cellular function. Low levels have been linked to weight loss, decreased energy production, and increased susceptibility to certain types of cancer as well as neurodegenerative disorders such as Alzheimer's disease. As such, monitoring serum concentrations through appropriate diagnostic tests is an important step for assessing thyroid functioning within patients. However, due to its role in regulating various functions across multiple tissues throughout the body (), additional research on its impact on cells within other organ systems should be conducted before drawing conclusions regarding its overall physiological effects on health status and disease progression.

Free T3 contributes to metabolic reactions throughout the body, including those of glycolysis and beta-oxidation in order to generate ATP molecules for cellular energy. This is essential for cognitive functioning of the central nervous system (CNS). Particular anticonvulsants such as carbamazepine and valproate are thought to work by reducing energy demand within neurons; therefore, these drugs require an efficient means for utilizing available energy from carbohydrates and fats so that it can be converted into ATP molecules. In order to reduce circulating free T3 levels, these anticonvulsant drugs utilize proteins with a higher affinity for binding such as TBG and transthyretin. Free T3 also impacts the rate of gene transcription by activating transcription factors, which alter cell growth and division as well as cellular differentiation. For example, it influences certain neurodegenerative disorders such Alzheimer's disease (AD). Furthermore, low levels of free T3 can also lead to decreased growth and development in children. As a result, monitoring serum concentrations through diagnostic tests is an important step for assessing thyroid functioning within patients. However, additional research on the effects of this hormone on other organ systems should be conducted before drawing conc