How Does the Thyroid Gland Function?

thyroid gland
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The thyroid gland is a butterfly-shaped organ, about 2 inches wide and weighing 10 to 20 grams, located in the base of the neck in front of the trachea (windpipe). Its job is to make hormones that are vitally important to the body’s metabolism and other critical functions.

The two major hormones released by the thyroid gland—thyroxine (T4) and triiodothyronine (T3)—help to regulate, among other things, the heart rate, body weight, muscle strength, breathing, body temperature, blood lipid levels, menstrual cycles, the nervous system, and energy expenditure.

In infants, thyroid hormones are crucial to the development of the brain and the skeletal system. So, a normally functioning thyroid gland is critical to the normal development of children, and to both the long-term and minute-to-minute well-being of adults. 

What the Thyroid Gland Does

It is the job of the thyroid gland to produce the thyroid hormones, T3 and T4. The distinguishing feature of the thyroid hormones is that they contain Iodine atoms—T3 has three iodine atoms, and T4 has four. Accordingly, the thyroid gland is unique in its specialized ability to take up iodine from the bloodstream, in order to incorporate it into the thyroid hormones.

All T4 in the body is produced by the thyroid gland—about 80 to 100 mcg per day. Roughly 10 times that amount of T4 (about 1000 mcg) is circulating in the blood. More than 99 percent of the circulating T4 is bound to proteins in the plasma (chiefly, to thyroid-binding globulin, TBG).

Only the small proportion of circulating T4 that is unbound (“free” T4) is available for use.

About 10 percent of the circulating T4 (equivalent to the amount of new T4 released daily by the thyroid gland) is degraded each day. Generally, around half of this amount is converted to T3 (by cleaving off one of the iodine atoms), and the remainder is converted to “reverse T3” (rT3, by cleaving off an iodine atom from a different location).

T3 is the active thyroid hormone, while rT3 is completely inactive.

Only about 20 percent of the T3 in the body is produced by the thyroid gland. The other 80 percent is produced from T4 within the tissues—particularly by the kidneys, liver, muscle, brain, skin, and placenta. The total production of T3 per day is about 30-40 mcg, and most of the T3 outside of the thyroid gland is located within the body’s cells. T3 is degraded much more rapidly than T4. 

A useful way to look at the thyroid hormones is to consider T4 to be a “pro-hormone” for T3—that is, to think of T4 as comprising a large pool of “potential” T3. Just the right amount of T4 is converted at just the right time to T3, according to the body’s minute-to-minute needs. T3 then does the work. To prevent the accumulation of too much circulating T4, “excess” T4 is converted to inactive rT3, which is metabolized by the tissues.

What the Thyroid Hormones Actually Do

Fundamentally, the thyroid hormones—specifically, T3—directly control the production of various proteins made by the body’s cells. T3 does this by binding to a cell’s DNA. 

Free T4 and free T3 circulating in the blood are available to immediately enter the body’s cells whenever they are needed.

Some of the intracellular T4 is converted to T3, and some of the T3 binds to specific T3-receptors in the nucleus of the cell. This bound T3 causes nuclear DNA to stimulate (or inhibit) the production of specific proteins. 

Different cells in the body have different kinds of T3-nuclear receptors, and in different concentrations, so the effect of T3 on a cell is quite variable from tissue to tissue, and under various circumstances. However, in all circumstances thyroid hormones act by regulating the function of DNA, causing it to increase or to slow the production of specific critical proteins.

Among these proteins are various enzymes that, in turn, control the behavior of many important bodily functions.

How the Thyroid System Is Regulated

As we have seen, the thyroid hormones are critical in both the long-term and the minute-to-minute control of many of the body’s vital functions. Any time a physiological system is this critical, we will see that nature has provided complex layers of regulation, aimed at assuring that that system is finely tuned to do what it needs to do, and that its function is controlled within a narrow range. These complex layers of regulatory overhead are certainly operative in the thyroid system.

Let’s have a brief look at the major “layers” of thyroid regulation.

The Pituitary-Thyroid Axis. The pituitary-thyroid axis provides the chief control over the thyroid gland itself. The pituitary gland (a gland located deep within the brain) releases a TSH, or thyroid stimulating hormone. The TSH causes the thyroid gland to increase its production and release of T3 and T4. At the same time, circulating thyroid hormone (specifically, T3) inhibits TSH production by the pituitary, thus forming a negative feedback loop. So, as T3 blood levels increase, TSH levels fall. This feedback loop operates to keep the production of thyroid hormone by the thyroid gland within a narrow range.

The Hypothalamus-Pituitary Axis. The release of TSH by the pituitary gland, in addition to responding to circulating T3, is also modulated by the release of TRH (thyrotropin-releasing hormone) by the hypothalamus. The release of TRH by the hypothalamus causes the pituitary gland to release more TSH, and thus, increases thyroid hormone production by the thyroid gland. 

The hypothalamus is a primitive part of the brain that coordinates many of the body’s basic functions, such as circadian rhythms, the neuroendocrine system, the autonomic nervous system, and several others. The hypothalamus responds to numerous stimuli including light and dark, smell, autonomic tone, several hormones, emotional stress, and neural inputs from the heart and gut. 

So thyroid hormone production is not dependent solely on TSH, but is also dependent on what the hypothalamus is “thinking and feeling” about the overall condition of the body and the environment.

Protein Binding of Thyroid Hormones. As mentioned, over 99% of the thyroid hormone in the circulation is bound to proteins in the blood, chiefly to TBG. Further, the protein-bound thyroid hormone is inactive. Only free T4 and T3 have any physiologic activity. 

This protein binding of the thyroid hormones serves several critical regulatory functions. It provides a large reservoir of circulating T4 to protect against a sudden reduction in the activity of the thyroid gland, while maintaining critical concentrations of free T3 and T4 within very narrow limits. 

If this T4 reservoir was unavailable, the tissues would be deprived of thyroid hormone within a few hours, if the thyroid gland were to become temporarily nonfunctional. 

The protein binding of the thyroid hormones also protects against any sudden increase in circulating free T3, should the tissues rapidly increase their conversion of T4 to T3. 

Intracellular Regulation of Thyroid Hormones. As we have seen, T3 and T4 do their important work inside of cells. Their normal functioning within cells—including their transport across the cell membrane from the blood to the interior of the cells, the conversion of T4 to T3, the crossing of T3 into the cell’s nucleus, and the binding of T3 to DNA—is dependent on a myriad of regulatory and transport proteins inside the cells whose identities and characteristics are still being discovered. 

Summary. The thyroid system is regulated at many levels. Large-scale regulation is achieved via the pituitary-thyroid axis, which (with modulation provided by the hypothalamus to take into account an overall assessment of the body’s general needs), determines how much thyroid hormone the thyroid gland produces and releases. The levels of free circulating thyroid hormones that are available to the tissues are buffered, on a minute-to-minute basis, by TBG and the other thyroid-binding blood proteins. And, on an instantaneous basis, the actual binding of T3 to T3-nuclear receptors, at the site of a cell’s DNA, appears to be regulated by several intracellular proteins. This system of regulation makes sure that plenty of thyroid hormone is available at all times to the tissues, but at the same time allows for extremely fine control of the thyroid-DNA interface within individual cells.

Disorders of the Thyroid

That’s a whole lot of regulation, at a whole lot of levels. And it means that thyroid disorders can occur with diseases affecting the thyroid gland itself, or with conditions affecting the hypothalamus, pituitary, or blood proteins, or even with disorders affecting the handling of thyroid hormones by various tissues of the body. 

In general, disorders of the thyroid system tend to cause thyroid function to become either underactive (hypothyroid), or overactive (hyperthyroid). In addition to these general problems, the thyroid gland can become grossly enlarged (a condition called a goiter). Cancer of the thyroid gland is also seen. Any of these conditions is potentially very serious.

The symptoms of thyroid disease can be quite variable. Symptoms of hypothyroidism often include dry skin, reduced heart rate, sluggishness, puffiness, skin changes, hair loss, lethargy, weight gain, and many others. Common symptoms of hyperthyroidism include elevated pulse, dry eyes, light sensitivity, insomnia, thinning hair, weakness, and tremors — but again there are many other symptoms that may be seen. Read more about the symptoms of thyroid disease

Diagnosing a thyroid problem requires a careful analysis of screening thyroid blood tests, and additional testing if a thyroid condition is suspected. Read about thyroid testing

In diagnosing a thyroid disorder, assessing the pituitary-thyroid axis is particularly critical. This can generally be done by measuring free serum T3 and T4, and serum TSH levels. If the TSH levels are elevated, it indicates that the thyroid gland is not producing enough hormone, and the pituitary is attempting to whip up its function. If the TSH levels are suppressed, it may mean that the thyroid gland is producing too much thyroid hormone.

In some cases, the proper interpretation of TSH levels can be tricky, and it can certainly be controversial. Read more about TSH testing and interpretation

The optimal treatment of thyroid disease can also be tricky, but generally the problem boils down to choosing among various effective treatments, rather than searching for a treatment that works at all. Read about some of the controversy regarding the treatment of hypothyroidism, and of hyperthyroidism.

A Word From Verywell

The thyroid gland, and the hormones it produces, are critically important to human development and to a healthy life. The critical nature of thyroid function is reflected in the complex mechanisms that nature has established for the regulation of thyroid hormones. Because the thyroid system is so important, it is crucial to properly diagnose and treat any disorders of the thyroid.

Sources:

Brent GA. Mechanisms of Thyroid Hormone Action. J Clin Invest 2012; 122:3035.

Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid 2014; 24:1670.

Mullur R, Liu YY, Brent GA. Thyroid Hormone Regulation of Metabolism. Physiol Rev 2014; 94:355.

Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26:1343.

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