The thyroid gland is a vital butterfly-shaped endocrine gland situated in the lower part of the neck. It is present in front and sides of the trachea, inferior to the larynx. It plays an essential role in the regulation of the basal metabolic rate (BMR), and stimulates somatic and psychic growth, besides having a vital role in calcium metabolism.
The thyroid weighs between 20 and 60 grams on average. It is surrounded by two fibrous capsules. The outer capsule is connected to the voice box muscles and many important vessels and nerves. There is the loose connective tissue between the inner and the outer capsule, so the thyroid can move and change its position when we swallow.
It is a gland consisting of two lobes, the right and the left lobes joined together by an intermediate structure, the isthmus. Sometimes a third lobe called the pyramidal lobe projects from the isthmus. It has a fibrous/fibromuscular band, i.e., levator glandular thyroidal running from the body of the hyoid to the isthmus.[rx] The lobes are 5 x 2.5 x 2.5 cm in dimension and weigh around 25 gm. It extends from the fifth cervical to the first thoracic vertebrae. The lobes extend from the middle of the thyroid cartilage to the fifth tracheal ring. The isthmus is 1.2 x 1.2 cm in dimensions and extends from second to third tracheal rings. It grows larger in females during the period of menstruation and pregnancy.
The lobes are conical in shape and have an apex, a base, three surfaces – lateral, medial, and posterolateral, and two borders – the anterior and posterior. The isthmus, however, has two surfaces – anterior and posterior and two borders – superior and inferior.
The lobes are related anteriorly to the skin, superficial and deep fascia, and platysma. Posteriorly, the lobes are associated with the laminae of the thyroid cartilage and tracheal rings, and laterally to the external carotid artery and internal jugular vein.
The thyroid gland is a richly vascular organ supplied by the superior and inferior thyroid arteries and sometimes by an additional artery known as the thyroid ima artery.[rx] The venous drainage is by superior, middle, and inferior thyroid veins. Sometimes a fourth thyroid vein might be present called the vein of Kocher. The nerve supply is mainly from middle cervical ganglion, but also partly from superior and inferior cervical ganglions.
Two capsules completely cover the thyroid gland. The true capsule is made up of fibro-elastic connective tissue. The false capsule is made up of the pre-tracheal layer of the deep cervical fascia. It consists of deep capillary plexus deep to the true capsule. Hence, it is crucial to remove the plexus with capsule during thyroidectomy.
Organ Systems Involved
Thyroid hormone induces effects on practically all nucleated cells in the human body, generally increasing their function and metabolism.
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Cardiac output, stroke volume, and resting heart rate increase through positive chronotropic and inotropic effects. Active thyroid hormone increases myocardial intracellular calcium to increase contraction force and speed. Concomitantly, vasculature in the skin, muscle, and heart dilate, resulting in decreased peripheral vascular resistance while blood volume increases through activation of the renin-angiotensin-aldosterone system.
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Basal metabolic rate (BMR), heat production, and oxygen consumption elevate through thyroid hormone activation of mitochondrial uncoupling proteins. Glucose and fatty acid uptake and oxidation also increase, which results in increased thermogenesis and necessitates increased heat dissipation. Heat intolerance in hyperthyroidism is attributable to this increase in thermogenesis. Compensation for increased thermogenesis is also mediated by thyroid hormone through increases in blood flow, sweating, and ventilation.
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Resting respiratory rate and minute ventilation undergo stimulation by active thyroid hormone, triiodothyronine (T3), to normalize arterial oxygen concentration in compensation for increased rates of oxidation. T3 also promotes oxygen delivery to the tissues by simulating erythropoietin and hemoglobin production and promoting folate and cobalamin absorption through the gastrointestinal tract.
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T3 is responsible for the development of fetal growth centers and linear bone growth, endochondral ossification, and epiphyseal bone center maturation following birth. Additionally, T3 simulates adult bone remodeling and degradation of mucopolysaccharides and fibronectin in extracellular connective tissue.
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T3 stimulates the nervous system resulting in increased wakefulness, alertness, and responsiveness to external stimuli. Thyroid hormone also stimulates the peripheral nervous system, resulting in increased peripheral reflexes and gastrointestinal tone, and motility.
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Thyroid hormone also plays a role in reproductive health and other endocrine organ function. It allows for the regulation of normal reproductive function in both men and women by regulating both the ovulatory cycle and spermatogenesis. Thyroid hormone also regulates pituitary function; growth hormone production and release are stimulated by thyroid hormone while inhibiting prolactin production and release. Additionally, renal clearance of many substances, including some medications, can be increased due to activated thyroid hormone stimulation of renal blood flow and glomerular filtration rate.[2][3]
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.
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 invertebrates, 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.
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).
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 a 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 much more active than T4.
thyroxine: A thyroid hormone also known as T4, thought to be a prohormone 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.
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.
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.
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:
- Inhibiting the osteoclast-mediated breakdown of bones.
- Stimulating osteoblastic activity to produce new bone tissue.
- 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.
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 thyroid 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.
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 thyrotropin-releasing hormone (TRH) secreted by the hypothalamus. Thyroid hormones provide negative feedback, inhibiting the secretion of TRH and TSH when blood levels are high.
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,[rx] which has a variable origin.[rx] The superior thyroid artery splits into anterior and posterior branches supplying the thyroid, and the inferior thyroid artery splits into superior and inferior branches.[rx] The superior and inferior thyroid arteries join together behind the outer part of the thyroid lobes.[rx] 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.[rx] Both arteries and veins form a plexus between the two layers of the capsule of the thyroid gland.[rx]
Lymphatic drainage frequently passes the laryngeal lymph nodes (located just above the isthmus), and the pretracheal and paratracheal lymph nodes.[rx] The gland receives sympathetic nerve supply from the superior, middle and inferior cervical ganglion of the sympathetic trunk.[rx] The gland receives parasympathetic nerve supply from the superior laryngeal nerve and the recurrent laryngeal nerve.[rx]
Structure
The thyroid gland is divided into lobules by the septae dipping from the capsule. The thyroid lobules consist of a large number of typical units called thyroid follicles.[rx] The thyroid follicles are the structural and functional units of a thyroid gland. These are spherical, and the wall is made up of a large number of cuboidal cells, the follicular cells. These follicular cells are the derivates of the endoderm and secrete thyroid hormone. The circulating form of this hormone is thyroxine, which is tetraiodothyronine (T4) along with a small quantity of triiodothyronine (T3). Even though most of T4 later converts to the more active form T3, both affect the target cells with varying degrees of stimulation. These hormones help in regulating the BMR of the body. In between these thyroid follicles or within the wall of the thyroid follicles, we find the small C cells, also know as Parafollicular cells. These are derived from neural crest cells and secrete polypeptide hormone known as calcitonin. The calcitonin helps in depositing calcium and phosphate in skeletal and other tissues leading to hypocalcemia. This function is the opposite of the parathormone.
These thyroid follicles act as storage compartments, filled with a substance called the colloid. This colloid is thyroglobulin, which is nothing but acidophilic secretory glycoprotein that is PAS-positive. These follicles are held together tightly within a delicate network of reticular fibers with an extensive capillary bed.
Function
- Metabolic. The thyroid hormones increase the basal metabolic rate and have effects on almost all body tissues.[rx] Appetite, the absorption of substances, and gut motility are all influenced by thyroid hormones.[rx] They increase the absorption in the gut, generation, uptake by cells, and breakdown of glucose.[rx] They stimulate the breakdown of fats, and increase the number of free fatty acids.[rx] Despite increasing free fatty acids, thyroid hormones decrease cholesterol levels, perhaps by increasing the rate of secretion of cholesterol in bile.[rx]
- 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.[rx] Combined, these factors increase blood flow and the body’s temperature.[rx]
- Developmental. Thyroid hormones are important for normal development.[rx] They increase the growth rate of young people,[rx] 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 the first few years of postnatal life[28]
- 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.[rx] Sexual function, including libido and the maintenance of a normal menstrual cycle, is influenced by thyroid hormones.[rx]
Some of the essential functions of the thyroid hormones are as follows:
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They regulate the basal metabolic rate (BMR).
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They play an important role in calcium metabolism
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They help in the overall development and function of CNS in children.[rx]
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They stimulate somatic and psychic growth.
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They stimulate heart rate and contraction.[rx]
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They help in the deposition of calcium and phosphate in bone and make the bones strong.
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They decrease the level of calcium in the blood.
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They regulate carbohydrate, fat, and protein metabolism.
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They also help in the metabolism of vitamins.
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They regulate the body temperature.
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They help degrade cholesterol and triglycerides.
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They maintain the electrolyte balance.
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They support the process of RBC formation.
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They enhance mitochondrial metabolism.
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They increase the oxygen consumptions by the cells and tissues.
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They influence the mood and behavior of a person.[rx]
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They stimulate gut motility.[rx]
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They also enhance the sensitivity of the beta-adrenergic receptors to catecholamines.
Thus the thyroid hormones act on almost all the cells of the body. They also take up a key role in the development, growth, and function of most of the tissues and organs of the body. One can also say that thyroid hormones are mandatory for the normal metabolic activity of all the cells of the body.
References
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