The Thyroid Gland

A butterfly-shaped organ, the thyroid gland is located anterior to the trachea, just inferior to the larynx. The medial region, called the isthmus, is flanked by wing-shaped left and right lobes. Each of the thyroid lobes are embedded with parathyroid glands, primarily on their posterior surfaces. The tissue of the thyroid gland is composed mostly of thyroid follicles. The follicles are made up of a central cavity filled with a sticky fluid called colloid. Surrounded by a wall of epithelial follicle cells, the colloid is the center of thyroid hormone production, and that production is dependent on the hormones’ essential and unique component: iodine.

Thyroid Gland
The thyroid gland is located in the neck where it wraps around the trachea. (a) Anterior view of the thyroid gland. (b) Posterior view of the thyroid gland. (c) The glandular tissue is composed primarily of thyroid follicles. The larger parafollicular cells often appear within the matrix of follicle cells. LM × 1332. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Part A of this figure is a diagram of the anterior view of the thyroid gland. The thyroid gland is a butterfly-shaped gland wrapping around the trachea. It narrows at its center, just under the thyroid cartilage of the larynx. This narrow area is called the isthmus of the thyroid. Two large arteries, the common carotid arteries, run parallel to the trachea on the outer border of the thyroid. A small artery enters the superior edge of the thyroid, near the isthmus, and branches throughout the two “wings” of the thyroid. Part B of this figure is a posterior view of the thyroid. The posterior view shows that the thyroid does not completely wrap around the posterior of the trachea. The posterior sides of the thyroid wings can be seen protruding from under the cricoid cartilage of the larynx. The posterior sides of the thyroid “wings” each contain two small, disc-shaped parathyroid glands embedded in the thyroid tissue. Within each wing, one disc is located superior to the other. These are labeled the left and right parathyroid glands. Just under the inferior parathyroid glands are two arteries that bring blood to the thyroid from the left and right subclavian arteries. Part C of this figure is a micrograph of thyroid tissue. The thyroid follicle cells are cuboidal epithelial cells. These cells form a ring around irregular-shaped cavities called follicles. The follicles contain light colored colloid. A larger parafollicular cell is embedded between two of the follicular cells near the edge of a follicle.

Synthesis and Release of Thyroid Hormones

Hormones are produced in the colloid when atoms of the mineral iodine attach to a glycoprotein, called thyroglobulin, that is secreted into the colloid by the follicle cells. The following steps outline the hormones’ assembly:

  1. Binding of TSH to its receptors in the follicle cells of the thyroid gland causes the cells to actively transport iodide ions (I) across their cell membrane, from the bloodstream into the cytosol. As a result, the concentration of iodide ions “trapped” in the follicular cells is many times higher than the concentration in the bloodstream.
  2. Iodide ions then move to the lumen of the follicle cells that border the colloid. There, the ions undergo oxidation (their negatively charged electrons are removed). The oxidation of two iodide ions (2 I) results in iodine (I2), which passes through the follicle cell membrane into the colloid.
  3. In the colloid, peroxidase enzymes link the iodine to the tyrosine amino acids in thyroglobulin to produce two intermediaries: a tyrosine attached to one iodine and a tyrosine attached to two iodines. When one of each of these intermediaries is linked by covalent bonds, the resulting compound is triiodothyronine (T3), a thyroid hormone with three iodines. Much more commonly, two copies of the second intermediary bond, forming tetraiodothyronine, also known as thyroxine (T4), a thyroid hormone with four iodines.

These hormones remain in the colloid center of the thyroid follicles until TSH stimulates endocytosis of colloid back into the follicle cells. There, lysosomal enzymes break apart the thyroglobulin colloid, releasing free T3 and T4, which diffuse across the follicle cell membrane and enter the bloodstream.

In the bloodstream, less than one percent of the circulating T3 and T4 remains unbound. This free T3 and T4 can cross the lipid bilayer of cell membranes and be taken up by cells. The remaining 99 percent of circulating T3 and T4 is bound to specialized transport proteins called thyroxine-binding globulins (TBGs), to albumin, or to other plasma proteins. This “packaging” prevents their free diffusion into body cells. When blood levels of T3 and T4 begin to decline, bound T3 and T4 are released from these plasma proteins and readily cross the membrane of target cells. T3 is more potent than T4, and many cells convert T4 to T3 through the removal of an iodine atom.

Regulation of TH Synthesis

The release of T3 and T4 from the thyroid gland is regulated by thyroid-stimulating hormone (TSH). Low blood levels of T3 and T4 stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus, which triggers secretion of TSH from the anterior pituitary. In turn, TSH stimulates the thyroid gland to secrete T3 and T4. The levels of TRH, TSH, T3, and T4 are regulated by a negative feedback system in which increasing levels of T3 and T4 decrease the production and secretion of TSH.

Classic Negative Feedback Loop
A classic negative feedback loop controls the regulation of thyroid hormone levels.

This diagram illustrates a negative feedback loop. It shows the general steps of a negative feedback loop at the center (imbalance, hormone release, correction, and negative feedback) using the example of the hormone cascade that regulates metabolic rate. The hypothalamus releases TRH in response to low metabolic rate and or low T three and T four concentrations in the blood (imbalance). This triggers TSH release by the pituitary (hormone release). The TSH travels to the thyroid where it triggers T three and T four release by the thyroid cells. T three and T four increase basal metabolic rate of the body cells and cause a rise in body temperature (the calorigenic effect). T three and T four then feed back to the hypothalamus and inhibits TRH and TSH release. If metabolic rate is high and or T three and T four concentrations are low, then the hypothalamus stops releasing TRH (negative feedback). As a result, the anterior pituitary will not release TSH and no T three or T four will be produced by the thyroid.

Functions of Thyroid Hormones

The thyroid hormones, T3 and T4, are often referred to as metabolic hormones because their levels influence the body’s basal metabolic rate, the amount of energy used by the body at rest. When T3 and T4 bind to intracellular receptors located on the mitochondria, they cause an increase in nutrient breakdown and the use of oxygen to produce ATP. In addition, T3 and T4 initiate the transcription of genes involved in glucose oxidation. Although these mechanisms prompt cells to produce more ATP, the process is inefficient, and an abnormally increased level of heat is released as a byproduct of these reactions. This so-called calorigenic effect (calor- = “heat”) raises body temperature.

Adequate levels of thyroid hormones are also required for protein synthesis and for fetal and childhood tissue development and growth. They are especially critical for normal development of the nervous system both in utero and in early childhood, and they continue to support neurological function in adults. As noted earlier, these thyroid hormones have a complex interrelationship with reproductive hormones, and deficiencies can influence libido, fertility, and other aspects of reproductive function. Finally, thyroid hormones increase the body’s sensitivity to catecholamines (epinephrine and norepinephrine) from the adrenal medulla by upregulation of receptors in the blood vessels. When levels of T3 and T4 hormones are excessive, this effect accelerates the heart rate, strengthens the heartbeat, and increases blood pressure. Because thyroid hormones regulate metabolism, heat production, protein synthesis, and many other body functions, thyroid disorders can have severe and widespread consequences.


The thyroid gland also secretes a hormone called calcitonin that is produced by the parafollicular cells (also called C cells) that stud the tissue between distinct follicles. Calcitonin is released in response to a rise in blood calcium levels. It appears to have a function in decreasing blood calcium concentrations by:

  • Inhibiting the activity of osteoclasts, bone cells that release calcium into the circulation by degrading bone matrix
  • Increasing osteoblastic activity
  • Decreasing calcium absorption in the intestines
  • Increasing calcium loss in the urine

However, these functions are usually not significant in maintaining calcium homeostasis, so the importance of calcitonin is not entirely understood. Pharmaceutical preparations of calcitonin are sometimes prescribed to reduce osteoclast activity in people with osteoporosis and to reduce the degradation of cartilage in people with osteoarthritis.

Thyroid Hormones
Associated hormones Chemical class Effect
Thyroxine (T4), triiodothyronine (T3) Amine Stimulate basal metabolic rate
Calcitonin Peptide Reduces blood Ca2+ levels

Of course, calcium is critical for many other biological processes. It is a second messenger in many signaling pathways, and is essential for muscle contraction, nerve impulse transmission, and blood clotting. Given these roles, it is not surprising that blood calcium levels are tightly regulated by the endocrine system. The organs involved in the regulation are the parathyroid glands.