The Thyroid Gland

Overview of the Thyroid Gland

The thyroid gland, in the anterior neck, controls body metabolism, protein synthesis, and a body’s responsiveness to other hormones.

Learning Objectives

Summarize the anatomy and purpose of the thyroid gland

Key Takeaways

Key Points

  • The thyroid gland controls how quickly the body uses energy, makes proteins, and controls how sensitive the body is to other hormones. It participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine (T3) and thyroxine (T4).
  • Hormones released from the thyroid regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body.
  • The thyroid also produces calcitonin, which plays a role in calcium homeostasis.
  • Hormonal output from the thyroid is regulated by thyroid-stimulating hormone (TSH) produced by the anterior pituitary, which itself is regulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus.
  • The thyroid gland (the thyroid in vertebrate anatomy ) is one of the largest endocrine glands.

Key Terms

  • thyroid-stimulating hormone: Also known as TSH or thyrotropin, this is a hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone, synthesized and secreted by thyrotrope cells in the anterior pituitary gland, that regulates the endocrine function of the thyroid gland.
  • thyroxine: A hormone (an iodine derivative of tyrosine), produced by the thyroid gland, that regulates cell metabolism and growth.

In vertebrates, the thyroid gland is one of the largest endocrine glands. It is found in the neck, below the thyroid cartilage that forms the laryngeal prominence, or Adam’s apple. The isthmus (the bridge between the two lobes of the thyroid) is located inferior to the cricoid cartilage. 

The thyroid gland controls how quickly the body uses energy, makes proteins, and controls how sensitive the body is to other hormones. It participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine (T3) and thyroxine (sometimes referred to as tetraiodothyronine (T4)). 

These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. T3 and T4 are synthesized from both iodine and tyrosine. 

The thyroid also produces calcitonin, which plays a role in calcium homeostasis. The hormonal output from the thyroid is regulated by thyroid-stimulating hormone (TSH) produced by the anterior pituitary, which itself is regulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus.

This is a diagram of the thyroid system. The hypothalamus is shown in the center of the brain. It secretes TRH that activates the anterior pituitary gland to release TSH that travels down the neck to they thyroid gland. There, T3 and T4 are activated and produce increased metabolism, growth and development, and increased catecholamine effect that flow down through the body. The thyroid glad is also depicted as having a negative mechanism that reports back to the anterior pituitary and hypothalamus.

Thyroid system: Thyroid function is regulated by the actions of the hypothalamus and pituitary gland. 

Anatomy of the Thyroid Gland

The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or wings, lobus dexter (right lobe) and lobus sinister (left lobe), connected via the isthmus. The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath. 

It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence, or Adam’s Apple), and extends inferiorly to approximately the fifth or sixth tracheal ring. It is difficult to demarcate the gland’s upper and lower border with vertebral levels because it moves in position in relation to these structures during swallowing.

Formation, Storage, and Release of Thyroid Hormones

Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and regulated by thyroid-stimulating hormone (TSH).

Learning Objectives

Describe the relationship between thyroxine (T4) and triiodothyronine (T3)

Key Takeaways

Key Points

  • Because the effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues ), T3 is three- to five-fold more active than T4.
  • Thyroxine is believed to be a pro- hormone and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase.
  • Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by thyroid-stimulating hormone secreted by the anterior pituitary gland.

Key Terms

  • thyroid-stimulating hormone: A hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body.
  • triiodothyronine: A thyroid hormone also known as T3 that plays a key role in many physiological processes and is the much more active than T4.
  • thyroxine: A thyroid hormone also known as T4, thought to be a pro-hormone and a reservoir for T3.

The thyroid hormones
thyroxine (T4) and triiodothyronine (T3) are produced from thyroid follicular cells within the thyroid gland, a process regulated by the thyroid-stimulating hormone secreted by the anterior pituitary gland.

Thyroglobulin, the pre-cursor of T4 and T3, is produced by the thyroid follicular cells before being secreted and stored in the follicular lumen. Iodide is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium is co-transported with iodide from the basolateral side of the membrane into the cell, and then concentrated in the thyroid follicles to about thirty times its concentration in the blood. 

Through a reaction with the enzyme thyroperoxidase, iodine is bound to tyrosine residues in the thyroglobulin molecules to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces T4. Combining one particle of MIT and one particle of DIT produces T3. 

Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically-active agents central to metabolic regulation. T3 is identical to T4, but it has one less iodine atom per molecule.

T4 is believed to be a pro-hormone and a reservoir for the more active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase.

This is a diagrammatic representation of thyroid hormone synthesis in a thyroid follicle. Sodium is co-transported with iodide from the basolateral side of the membrane into the cell, and then concentrated in the thyroid follicles to about thirty times its concentration in the blood.

Thyroid hormone: Diagrammatic representation of thyroid hormone synthesis in a thyroid follicle. 

Effects of Iodine Deficiency

If there is a deficiency of dietary iodine, the thyroid will not be able to make thyroid hormone. A lack of thyroid hormone will lead to decreased negative feedback on the pituitary, which in turn, will lead to increased production of thyroid-stimulating hormone, which causes the thyroid to enlarge (goiter). 

This enlarged endemic colloid goiter has the effect of increasing the thyroid’s ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone.

Action of Thyroid Hormones

The primary function of the thyroid is to produce the hormones triiodothyronine (T3), thyroxine (T4), and calcitonin.

Learning Objectives

List the actions of thyroid hormones

Key Takeaways

Key Points

  • T4 is converted to T3 by peripheral organs such as the liver, kidney, and spleen.
  • Triiodothyronine (T3) is several times more powerful than T4, which is largely a pro- hormone.
  • The regulation of actin polymerization by T4 is critical to cell migration in neurons and glial cells and is important for brain development.
  • Thyroid hormones play an important role in regulating metabolic rate and body temperature.

Key Terms

  • thyroxine: A hormone (an iodine derivative of tyrosine) produced by the thyroid gland that regulates cell metabolism and growth.

Triiodothyronine (T3) and thyroxine (T4) are enzymes produced by the thyroid gland. T4 is thought to be a pro-hormone to the more metabolically active T3. T4 is converted to T3 in tissues as required by deiodinase enzymes.

Calcitonin is another hormone released by the thyroid gland that is responsible for modulating blood calcium levels in conjunction with parathyroid hormone, which is released from the parathyroid.

Effect of Thyroid Hormones on Metabolism

The main activity of the thyroid hormones T3 and T4 is to boost the basal metabolic rates of proteins, fats, and carbohydrates as well as vitamins.

This is a diagram of the thyroid system. The hypothalamus is shown in the center of the brain. It secretes TRH that activates the anterior pituitary gland to release TSH that travels down the neck to they thyroid gland. There, T3 and T4 are activated and produce increased metabolism, growth and development, and increased catecholamine effect that flow down through the body. The thyroid glad is also depicted as having a negative mechanism that reports back to the anterior pituiatary and hypothalamus.

Thyroid system: An overview of the thyroid system.

Effect of Thyroid Hormones on Body Temperature

Thyroid hormones affect the dilation of blood vessels, which in turn affects the rate at which heat can escape the body. The more dilated blood vessels are, the faster heat can escape. 

A person who suffers from hyperthyroidism (an over-active thyroid) will experience a fever; conversely, a person who suffers from hypothyroidism (a less active thyroid) will experience a decrease in body temperature.

Action of Thyroid Hormones on the Developing Fetus

The cells of the developing brain are a major target for T3 and T4. Thyroid hormones play a particularly crucial role in brain maturation during fetal development by regulating actin polymerization during neuronal development.

Action of Thyroid Hormones in Blood

In the blood, T4 and T3 are partially bound to thyroxine-binding globulin (TBG), transthyretin, and albumin. Only a very small fraction of the circulating hormone is free—T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity. 

As with the steroid hormones, thyroid hormones are lipophillic and can cross the cell membrane and bind to intracellular receptors, which act alone as transcription factors or in association with other factors to modulate DNA transcription.

Calcitonin Activity

Calcitonin acts to lower blood calcium levels in three ways:

  1. Inhibiting the osteoclast-mediated breakdown of bones.
  2. Stimulating osteoblastic activity to produce new bone tissue.
  3. Inhibiting re-absorption of calcium in the kidneys.

Control of Thyroid Hormone Release

The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH) that is released from the anterior pituitary.

Learning Objectives

Explain how thyroid hormone release is controlled

Key Takeaways

Key Points

  • Thyroid hormones are released from the thyroid under the control of thyroid stimulating hormone (TSH).
  • TSH is secreted by the anterior pituitary gland and is itself under the control of thyrotropin-releasing hormone (TRH).
  • TRH is secreted by the hypothalamus.
  • Both TSH and TRH secretion are inhibited when elevated thyroid hormone levels are detected in the blood and provide negative feedback to the hypothalamus and anterior pituitary gland.

Key Terms

  • thyroid-stimulating hormone: A hormone released from the anterior pituitary gland that stimulates the release of thyorid hormones.
  • thyrotropin-releasing hormone: A hormone released from the hypothalamus that stimulates thyroid-stimulating hormone production from the anterior pituitary gland.

The production of thyroxine (T4) and triiodothyronine (T3) is primarily regulated by thyroid-stimulating hormone (TSH) that is released from the anterior pituitary gland. TSH release, in turn, stimulates the hypothalamus to secrete thyrotropin-releasing hormone (TRH). This results in increased metabolism, growth, development and the activation of numerous other systems controlled by thyroid hormones.

Thyroid hormones also provide negative feedback to the hypothalamus and anterior pituitary gland. When thyroid levels in the blood are elevated TSH and TRH production is reduced. Excessive TRH can also inhibit the production of further TRH.

This is a diagram of the thyroid system. It shows how thyroid hormones are produced from the thyroid under the influence of thyroid-stimulating hormone (TSH) from the anterior pituitary gland, which is itself under the control of thyroptropin-releasing hormone (TRH) secreted by the hypothalamus. Thyroid hormones provide negative feedback, inhibiting secretion of TRH and TSH when blood levels are high.

The thyroid system: Thyroid hormones are produced from the thyroid under the influence of thyroid-stimulating hormone (TSH) from the anterior pituitary gland, which is itself under the control of thyroptropin-releasing hormone (TRH) secreted by the hypothalamus. Thyroid hormones provide negative feedback, inhibiting secretion of TRH and TSH when blood levels are high.