Thyroid

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells, and occasional parafollicular cells that surround a lumen containing colloid.
The thyroid gland secretes three hormones: the two thyroid hormonestriiodothyronine and thyroxine and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis and growth and development in children. Calcitonin plays a role in calcium homeostasis.
Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone, which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone, which is produced by the hypothalamus.
Thyroid disorders include hyperthyroidism, hypothyroidism, thyroid inflammation, thyroid enlargement, thyroid nodules, and thyroid cancer. Hyperthyroidism is characterized by excessive secretion of thyroid hormones: the most common cause is the autoimmune disorder Graves' disease. Hypothyroidism is characterized by a deficient secretion of thyroid hormones: the most common cause is iodine deficiency. In iodine-deficient regions, hypothyroidism is the leading cause of preventable intellectual disability in children. In iodine-sufficient regions, the most common cause of hypothyroidism is the autoimmune disorder Hashimoto's thyroiditis.

Structure

Features

The thyroid gland is a butterfly-shaped organ composed of two lobes, left and right, connected by a narrow tissue band, called an "isthmus". It weighs 25 grams in adults, with each lobe being about 5 cm long, 3 cm wide, and 2 cm thick and the isthmus about 1.25 cm in height and width. The gland is usually larger in women than in men, and increases in size during pregnancy.
The thyroid is near the front of the neck, lying against and around the front of the larynx and trachea. The thyroid cartilage and cricoid cartilage lie just above the gland, below the Adam's apple. The isthmus extends from the second to third rings of the trachea, with the uppermost part of the lobes extending to the thyroid cartilage and the lowermost around the fourth to sixth tracheal rings. The infrahyoid muscles lie in front of the gland and the sternocleidomastoid muscle to the side. Behind the outer wings of the thyroid lie the two carotid arteries. The trachea, larynx, lower pharynx and esophagus all lie behind the thyroid. In this region, the recurrent laryngeal nerve and the inferior thyroid artery pass next to or in the ligament. Typically, four parathyroid glands, two on each side, lie on each side between the two layers of the thyroid capsule, at the back of the thyroid lobes.
The thyroid gland is covered by a thin fibrous capsule, which has an inner and an outer layer. The inner layer extrudes into the gland and forms the septa that divide the thyroid tissue into microscopic lobules. The outer layer is continuous with the pretracheal fascia, attaching the gland to the cricoid and thyroid cartilages via a thickening of the fascia to form the posterior suspensory ligament of thyroid gland, also known as Berry's ligament. This causes the thyroid to move up and down with the movement of these cartilages when swallowing occurs.

Blood, lymph and nerve supply

The thyroid is supplied with arterial blood from the superior thyroid artery, a branch of the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, and sometimes by an anatomical variant the thyroid ima artery, which has a variable origin. The superior thyroid artery splits into anterior and posterior branches supplying the thyroid, and the inferior thyroid artery splits into superior and inferior branches. The superior and inferior thyroid arteries join behind the outer part of the thyroid lobes. The venous blood is drained via superior and middle thyroid veins, which drain to the internal jugular vein, and via the inferior thyroid veins. The inferior thyroid veins originate in a network of veins and drain into the left and right brachiocephalic veins. Both arteries and veins form a plexus between the two layers of the capsule of the thyroid gland.
Lymphatic drainage frequently passes the prelaryngeal lymph nodes and the pretracheal and paratracheal lymph nodes. The gland receives sympathetic nerve supply from the superior, middle and inferior cervical ganglion of the sympathetic trunk. The gland receives parasympathetic nerve supply from the superior laryngeal nerve and the recurrent laryngeal nerve.

Variation

There are many variants in the size and shape of the thyroid gland, and in the position of the embedded parathyroid glands.
Sometimes there is a third lobe present called the pyramidal lobe. When present, this lobe often stretches up to the hyoid bone from the thyroid isthmus and may be one to several divided lobes. The presence of this lobe ranges in reported studies from 18.3% to 44.6%. It was shown to more often arise from the left side and occasionally separated. The pyramidal lobe is also known as Lalouette's pyramid. The pyramidal lobe is a remnant of the thyroglossal duct, which usually wastes away during the thyroid gland's descent. Small accessory thyroid glands may in fact occur anywhere along the thyroglossal duct, from the foramen cecum of the tongue to the position of the thyroid in the adult. A small horn at the back of the thyroid lobes, usually close to the recurrent laryngeal nerve and the inferior thyroid artery, is called Zuckerkandl's tubercle.
Other variants include a levator muscle of thyroid gland, connecting the isthmus to the body of the hyoid bone, and the presence of the small thyroid ima artery.

Microanatomy

At the microscopic level, there are three primary features of the thyroid—thyroid follicles, thyroid follicular cells, and parafollicular cells, first discovered by Geoffery Websterson in 1664.
;Follicles
Thyroid follicles are small spherical groupings of cells 0.02–0.9mm in diameter that play the main role in thyroid function. They consist of a rim that has a rich blood supply, nerve and lymphatic presence, that surrounds a core of colloid that consists mostly of thyroid hormone precursor proteins called thyroglobulin, an iodinated glycoprotein.
;Follicular cells
The core of a follicle is surrounded by a single layer of follicular cells. When stimulated by thyroid stimulating hormone, these secrete the thyroid hormones T₃ and T₄. They do this by transporting and metabolising the thyroglobulin contained in the colloid. Follicular cells vary in shape from flat to cuboid to columnar, depending on how active they are.
;Follicular lumen
The follicular lumen is the fluid-filled space within a follicle of the thyroid gland. There are hundreds of follicles within the thyroid gland. A follicle is formed by a spherical arrangement of follicular cells. The follicular lumen is filled with colloid, a concentrated solution of thyroglobulin and is the site of synthesis of the thyroid hormones thyroxine and triiodothyronine.
;Parafollicular cells
Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells. These cells secrete calcitonin and so are also called C cells.

Development

In the development of the embryo, at 3–4 weeks gestational age, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue between the tuberculum impar and the copula linguae. The copula soon becomes covered over by the hypopharyngeal eminence at a point later indicated by the foramen cecum. The thyroid then descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct. Over the next few weeks, it migrates to the base of the neck, passing in front of the hyoid bone. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct. At the end of the fifth week the thyroglossal duct degenerates, and over the following two weeks the detached thyroid migrates to its final position.
The fetal hypothalamus and pituitary start to secrete thyrotropin-releasing hormone and thyroid-stimulating hormone. TSH is first measurable at 11 weeks. By 18–20 weeks, the production of thyroxine reaches a clinically significant and self-sufficient level. Fetal triiodothyronine remains low, less than 15 ng/dL until 30 weeks, and increases to 50 ng/dL at full-term. The fetus needs to be self-sufficient in thyroid hormones in order to guard against neurodevelopmental disorders that would arise from maternal hypothyroidism. The presence of sufficient iodine is essential for healthy neurodevelopment.
The neuroendocrine parafollicular cells, also known as C cells, responsible for the production of calcitonin, are derived from foregut endoderm. This part of the thyroid then first forms as the ultimopharyngeal body, which begins in the ventral fourth pharyngeal pouch and joins the primordial thyroid gland during its descent to its final location.
Aberrations in prenatal development can result in various forms of thyroid dysgenesis which can cause congenital hypothyroidism, and if untreated this can lead to cretinism.

Function

Thyroid hormones

The primary function of the thyroid is the production of the iodine-containing thyroid hormones, triiodothyronine and thyroxine or tetraiodothyronine and the peptide hormone calcitonin. The thyroid hormones are created from iodine and tyrosine. T₃ is so named because it contains three atoms of iodine per molecule and T₄ contains four atoms of iodine per molecule. The thyroid hormones have a wide range of effects on the human body. These include:

Metabolic. The thyroid hormones increase the basal metabolic rate and have effects on almost all body tissues. Appetite, the absorption of substances, and gut motility are all influenced by thyroid hormones. They increase the absorption in the gut, generation, uptake by cells, and breakdown of glucose. They stimulate the breakdown of fats, and increase the number of free fatty acids. Despite increasing free fatty acids, thyroid hormones decrease cholesterol levels, perhaps by increasing the rate of secretion of cholesterol in bile.
Cardiovascular. The hormones increase the rate and strength of the heartbeat. They increase the rate of breathing, intake and consumption of oxygen, and increase the activity of mitochondria. Combined, these factors increase blood flow and the body's temperature.
Developmental. Thyroid hormones are important for normal development. They increase the growth rate of young people, and cells of the developing brain are a major target for the thyroid hormones T₃ and T₄. Thyroid hormones play a particularly crucial role in brain maturation during fetal development and first few years of postnatal life
Other. The thyroid hormones also play a role in maintaining normal sexual function, sleep, and thought patterns. Increased levels are associated with increased speed of thought generation but decreased focus. Sexual function, including libido and the maintenance of a normal menstrual cycle, are influenced by thyroid hormones.

After secretion, only a very small proportion of the thyroid hormones travel freely in the blood. Most are bound to thyroxine-binding globulin, transthyretin, and albumin. Only the 0.03% of T₄ and 0.3% of T₃ traveling freely have hormonal activity. In addition, up to 85% of the T₃ in blood is produced following conversion from T₄ by iodothyronine deiodinases in organs around the body.
Thyroid hormones act by crossing the cell membrane and binding to intracellular nuclear thyroid hormone receptors TR-α₁, TR-α₂, TR-β₁, and TR-β₂, which bind with hormone response elements and transcription factors to modulate DNA transcription. In addition to these actions on DNA, the thyroid hormones also act within the cell membrane or within cytoplasm via reactions with enzymes, including calcium ATPase, adenylyl cyclase, and glucose transporters.