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The thyroid, or thyroid gland, is an
endocrine gland The endocrine system is a network of glands and organs located throughout the body. Along with the nervous system, it makes the neuroendocrine system, which controls and regulates many of the body's functions. Endocrine glands are ductless gland ...
in
vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
. In humans, it is a butterfly-shaped gland located in the neck below the
Adam's apple The Adam's apple is the protrusion in the neck formed by the angle of the thyroid cartilage surrounding the larynx, typically visible in men, less frequently in women. The prominence of the Adam's apple increases in some men as a secondary mal ...
. It consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus (: isthmi). Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional
parafollicular cell Parafollicular cells, also called C cells, are neuroendocrine cells in the thyroid. They are called C cells because the primary function of these cells is to secrete calcitonin. They are located adjacent to the thyroid follicles and reside in the ...
s that surround a lumen containing
colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others exte ...
. The thyroid gland secretes three hormones: the two
thyroid hormones File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 ...
triiodothyronine (T3) and thyroxine (T4)and a
peptide hormone Peptide hormones are hormones composed of peptide molecules. These hormones influence the endocrine system of animals, including humans. Most hormones are classified as either amino-acid-based hormones (amines, peptides, or proteins) or steroid h ...
,
calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
. The thyroid hormones influence the
metabolic rate Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
and
protein synthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critica ...
and growth and development in children. Calcitonin plays a role in
calcium homeostasis Calcium metabolism is the movement and regulation of calcium ions (Ca2+) ''in'' (via the gut) and ''out'' (via the gut and kidneys) of the body, and ''between'' body compartments: the blood plasma, the extracellular and intracellular fluids, an ...
. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the
anterior pituitary The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
gland. TSH is regulated by
thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) as well as prolactin from the anterior pituitary. TRH has been used ...
(TRH), which is produced by the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. Thyroid disorders include
hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...
,
hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
, thyroid
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
( thyroiditis), thyroid enlargement (
goitre A goitre (British English), or goiter (American English), is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are ...
), thyroid nodules, and
thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, ...
. Hyperthyroidism is characterized by excessive secretion of thyroid hormones: the most common cause is the
autoimmune disorder An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...
Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...
. Hypothyroidism is characterized by a deficient secretion of thyroid hormones: the most common cause is
iodine deficiency Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated ...
. In iodine-deficient regions, hypothyroidism (due to iodine deficiency) is the leading cause of preventable
intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...
in children. In iodine-sufficient regions, the most common cause of hypothyroidism is the autoimmune disorder
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, Hashimoto's disease and autoimmune thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over ti ...
.


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 The larynx (), commonly called the voice box, is an organ (anatomy), organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal ...
and
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
. The thyroid cartilage and cricoid cartilage lie just above the gland, below the
Adam's apple The Adam's apple is the protrusion in the neck formed by the angle of the thyroid cartilage surrounding the larynx, typically visible in men, less frequently in women. The prominence of the Adam's apple increases in some men as a secondary mal ...
. 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 The sternocleidomastoid muscle is one of the largest and most superficial cervical muscles. The primary actions of the muscle are rotation of the head to the opposite side and Anatomical terms of motion#Flexion and extension, flexion of the neck. ...
to the side. Behind the outer wings of the thyroid lie the two
carotid arteries In anatomy, the left and right common carotid arteries (carotids) () are arteries that supply the head and neck with oxygenated blood; they divide in the neck to form the external and internal carotid arteries. Structure The common carotid ...
. The trachea, larynx, lower pharynx and esophagus all lie behind the thyroid. In this region, the
recurrent laryngeal nerve The recurrent laryngeal nerve (RLN), also known as nervus recurrens, is a branch of the vagus nerve ( cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recur ...
and the inferior thyroid artery pass next to or in the ligament. Typically, four
parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...
s, 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 SEPTA, the Southeastern Pennsylvania Transportation Authority, is a regional public transportation authority that operates bus, rapid transit, commuter rail, light rail, and electric trolleybus services for nearly four million people througho ...
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 The external carotid artery is the major artery of the head and upper neck. It arises from the common carotid artery. It terminates by splitting into the superficial temporal and maxillary artery within the parotid gland. Structure Origin T ...
, and the
inferior thyroid artery The inferior thyroid artery is an artery in the neck. It arises from the thyrocervical trunk and passes upward, in front of the vertebral artery and longus colli muscle. It then turns medially behind the carotid sheath and its contents, and a ...
, 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 The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve. It begins in the posteri ...
, and via the inferior thyroid veins. The inferior thyroid veins originate in a network of veins and drain into the left and right
brachiocephalic vein The left and right brachiocephalic veins (previously called innominate veins) are major veins in the Thorax, upper chest, formed by the union of the ipsilateral internal jugular vein and subclavian vein (the so-called venous angle) behind the ster ...
s. Both arteries and veins form a plexus between the two layers of the capsule of the thyroid gland.
Lymph Lymph () is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the ori ...
atic drainage frequently passes the prelaryngeal lymph nodes (located just above the isthmus) 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 sympathetic trunk (sympathetic chain, gangliated cord) is a paired bundle of nerve fibers that run from the base of the skull to the coccyx. It is a major component of the sympathetic nervous system. Structure The sympathetic trunk lies just ...
. The gland receives parasympathetic nerve supply from the superior laryngeal nerve and the
recurrent laryngeal nerve The recurrent laryngeal nerve (RLN), also known as nervus recurrens, is a branch of the vagus nerve ( cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recur ...
.


Variation

There are many
variants Variant may refer to: Arts and entertainment * ''Variant'' (magazine), a former British cultural magazine * Variant cover, an issue of comic books with varying cover art * ''Variant'' (novel), a novel by Robison Wells * " The Variant", 2021 epis ...
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 The hyoid-bone (lingual-bone or tongue-bone) () is a horseshoe-shaped bone situated in the anterior midline of the neck between the chin and the thyroid-cartilage. At rest, it lies between the base of the mandible and the third cervical verte ...
, 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 cell Thyroid follicular cells (also called thyroid epithelial cells or thyrocytes) are the major cell type in the thyroid gland, and are responsible for the production and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). They ...
s, and
parafollicular cell Parafollicular cells, also called C cells, are neuroendocrine cells in the thyroid. They are called C cells because the primary function of these cells is to secrete calcitonin. They are located adjacent to the thyroid follicles and reside in the ...
s, 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 A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others exte ...
that consists mostly of thyroid hormone precursor proteins called
thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
, an iodinated
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
. ;Follicular cells The core of a follicle is surrounded by a single layer of follicular cells. When stimulated by thyroid stimulating hormone (TSH), 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 Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
and is the site of synthesis of the thyroid hormones
thyroxine Thyroxine, also known as T4, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T3). Thyroxine and its acti ...
(T4) and
triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyroxi ...
(T3). ;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 Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
and so are also called C cells.


Development

In the development of the embryo, at 3–4 weeks
gestational age In obstetrics, gestational age is a measure of the age of a pregnancy taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method, if available. Such metho ...
, the thyroid gland appears as an
epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
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 In medicine or biology, a diverticulum is an outpouching of a hollow (or a fluid-filled) structure in the body. Depending upon which layers of the structure are involved, diverticula are described as being either true or false. In medicine, t ...
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 A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
and
pituitary The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus control much of th ...
start to secrete
thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) as well as prolactin from the anterior pituitary. TRH has been used ...
(TRH) and thyroid-stimulating hormone (TSH). TSH is first measurable at 11 weeks. By 18–20 weeks, the production of
thyroxine Thyroxine, also known as T4, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T3). Thyroxine and its acti ...
(T4) reaches a clinically significant and self-sufficient level. Fetal
triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyroxi ...
(T3) remains low, less than 15 ng/dL until 30 weeks, and increases to 50 ng/dL at full-term. The
fetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...
needs to be self-sufficient in thyroid hormones in order to guard against
neurodevelopmental disorder Neurodevelopmental disorders are a group of mental conditions negatively affecting the development of the nervous system, which includes the brain and spinal cord. According to the American Psychiatric Association Diagnostic and Statistical Manu ...
s that would arise from maternal hypothyroidism. The presence of sufficient iodine is essential for healthy neurodevelopment. The
neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they b ...
parafollicular cell Parafollicular cells, also called C cells, are neuroendocrine cells in the thyroid. They are called C cells because the primary function of these cells is to secrete calcitonin. They are located adjacent to the thyroid follicles and reside in the ...
s, also known as C cells, responsible for the production of
calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
, 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 Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal de ...
can result in various forms of thyroid dysgenesis which can cause
congenital hypothyroidism Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with co ...
, 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 File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 ...
,
triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyroxi ...
(T3) and
thyroxine Thyroxine, also known as T4, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T3). Thyroxine and its acti ...
or tetraiodothyronine (T4) and the
peptide hormone Peptide hormones are hormones composed of peptide molecules. These hormones influence the endocrine system of animals, including humans. Most hormones are classified as either amino-acid-based hormones (amines, peptides, or proteins) or steroid h ...
calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
. The thyroid hormones are created from
iodine Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at , and boils to a vi ...
and
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
. 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 Basal metabolic rate (BMR) is the rate of energy expenditure per unit time by endothermic animals at rest.. In other words it is the energy required by body organs to perform normal It is reported in energy units per unit time ranging from watt ( ...
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 A generation is all of the people born and living at about the same time, regarded collectively. It also is "the average period, generally considered to be about 20–⁠30 years, during which children are born and grow up, become adults, and b ...
, uptake by cells, and breakdown of glucose. They stimulate the breakdown of fats, and increase the number of
free fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
s. Despite increasing free fatty acids, thyroid hormones decrease
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
levels, perhaps by increasing the rate of secretion of cholesterol in
bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
. * 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 A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
. 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 * 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 The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
, 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 Thyroxine-binding globulin (TBG) is a globulin protein encoded by the ''SERPINA7'' gene in humans. TBG binds thyroid hormones in circulation. It is one of three transport proteins (along with transthyretin and serum albumin) responsible for ...
(about 70%),
transthyretin Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol' ...
(10%), and
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...
(15%). 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 The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
and binding to
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
nuclear Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space *Nuclear ...
thyroid hormone receptors TR-α1, TR-α2, TR-β1, and TR-β2, which bind with hormone response elements and
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s 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
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s, including calcium ATPase,
adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...
, and
glucose transporter Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporte ...
s.


Hormone production

The thyroid hormones are created from
thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
. This is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
within the colloid in the follicular lumen that is originally created within the
rough endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little n ...
of follicular cells and then transported into the follicular lumen. Thyroglobulin contains 123 units of
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
, which reacts with iodine within the follicular lumen.
Iodine Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at , and boils to a vi ...
is essential for the production of the thyroid hormones. Iodine (I0) travels in the blood as
iodide An iodide ion is I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered as a component of iodized salt, which many governments mandate. Worldwide, iodine deficiency ...
(I), which is taken up into the follicular cells by a
sodium-iodide symporter The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the ''SLC5A5'' gene. It is a transmembrane glycoprotein with a molecular weight of 87 kAtomic mass unit, Da and 13 transmem ...
. This is an
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
on the cell membrane which in the same action transports two sodium ions and an iodide ion into the cell. Iodide then travels from within the cell into the lumen, through the action of pendrin, an iodide-chloride
antiporter An antiporter (also called exchanger or counter-transporter) is an integral membrane protein that uses secondary active transport to move two or more molecules in opposite directions across a phospholipid membrane. It is a type of cotransporte ...
. In the follicular lumen, the iodide is then
oxidized Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
to iodine. This makes it more reactive, and the iodine is attached to the active tyrosine units in thyroglobulin by the enzyme
thyroid peroxidase Thyroid peroxidase, also called thyroperoxidase (TPO), thyroid specific peroxidase or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms ...
. This forms the precursors of thyroid hormones
monoiodotyrosine 3-Iodotyrosine is an intermediate in the synthesis of thyroid hormones which is derived from iodination of tyrosine at the meta-position of the benzene ring. One unit can combine with diiodotyrosine to form triiodothyronine, as occurs in the c ...
(MIT), and
diiodotyrosine Diiodotyrosine (DIT) is a precursor in the production of thyroid hormone, and results from iodization of monoiodotyrosine at the other meta- position on the phenol ring. Function DIT is a modulator of the enzyme thyroid peroxidase (which is inv ...
(DIT). When the follicular cells are stimulated by thyroid-stimulating hormone, the follicular cells reabsorb thyroglobulin from the follicular lumen. The iodinated tyrosines are cleaved, forming the thyroid hormones T4, T3, DIT, MIT, and traces of
reverse triiodothyronine Reverse triiodothyronine, also known as rT3, is an isomer of triiodothyronine (T3). Reverse T3 is the third-most common iodothyronine the thyroid gland releases into the bloodstream, at 0.9%; tetraiodothyronine (levothyroxine, T4) constitutes 90% ...
. T3 and T4 are released into the blood. The hormones secreted from the gland are about 80–90% T4 and about 10–20% T3.How Your Thyroid Works: A Delicate Feedback Mechanism
Updated 2009-05-21.
The thyroid gland
in ''Endocrinology: An Integrated Approach'' by Stephen Nussey and Saffron Whitehead (2001) Published by BIOS Scientific Publishers Ltd.
Deiodinase enzymes in peripheral tissues remove the iodine from MIT and DIT and convert T4 to T3 and RT3. This is a major source of both RT3 (95%) and T3 (87%) in peripheral tissues.


Regulation

The production of thyroxine and triiodothyronine is primarily regulated by thyroid-stimulating hormone (TSH), released by the
anterior pituitary The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
gland. TSH release in turn is stimulated by thyrotropin releasing hormone (TRH), released in a pulsatile manner from the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. The thyroid hormones provide
negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...
to the thyrotropes TSH and TRH: when the thyroid hormones are high, TSH production is suppressed. This negative feedback also occurs when levels of TSH are high, causing TRH production to be suppressed. TRH is secreted at an increased rate in situations such as cold exposure in order to stimulate
thermogenesis Thermogenesis is the process of heat production in organisms. It occurs in all warm-blooded animals, and also in a few species of thermogenic plants such as the Eastern skunk cabbage, the Voodoo lily ('' Sauromatum venosum''), and the giant w ...
. In addition to being suppressed by the presence of thyroid hormones, TSH production is blunted by
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
,
somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
, and
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
s.


Calcitonin

The thyroid gland also produces the hormone
calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
, which helps regulate blood
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
levels. Parafollicular cells produce calcitonin in response to
high blood calcium Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...
. Calcitonin decreases the release of calcium from bone, by decreasing the activity of
osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...
s, cells which break down bone. Bone is constantly reabsorbed by osteoclasts and created by
osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...
s, so calcitonin effectively stimulates movement of calcium into
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
. The effects of calcitonin are opposite those of the parathyroid hormone (PTH) produced in the parathyroid glands. However, calcitonin seems far less essential than PTH, since calcium metabolism remains clinically normal after removal of the thyroid (
thyroidectomy A thyroidectomy is an operation that involves the surgery, surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other ...
), but not the
parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...
s.


Gene and protein expression

About 20,000 protein-coding genes are expressed in human cells: 70% of these genes are expressed in thyroid cells. Two-hundred and fifty of these genes are more specifically expressed in the thyroid, and about 20 genes are highly thyroid specific. In the follicular cells, the proteins synthesized by these genes direct thyroid hormone synthesis—
thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
, TPO, and IYD; while in the parafollicular c-cells, they direct calcitonin synthesis— CALCA, and CALCB.


Clinical significance

General practitioner A general practitioner (GP) is a doctor who is a Consultant (medicine), consultant in general practice. GPs have distinct expertise and experience in providing whole person medical care, whilst managing the complexity, uncertainty and risk ass ...
s, and
internal medicine Internal medicine, also known as general medicine in Commonwealth nations, is a medical specialty for medical doctors focused on the prevention, diagnosis, and treatment of diseases in adults. Its namesake stems from "treatment of diseases of ...
specialists play a role in identifying and monitoring the treatment of thyroid disease. Endocrinology, Endocrinologists and thyroidologists are thyroid specialists. Thyroid surgeons or otolaryngologists are responsible for the surgical management of thyroid disease.


Functional disorders


Hyperthyroidism

Excessive production of the thyroid hormones is called
hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...
. Causes include
Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...
, toxic multinodular goitre, solitary thyroid adenoma, inflammation, and a pituitary adenoma which secretes excess TSH. Another cause is excess iodine availability, either from excess ingestion, induced by the drug amiodarone, or following iodinated contrast medical imaging, imaging. Hyperthyroidism often causes a variety of symptoms#Types, non-specific symptoms including weight loss, increased appetite, insomnia, decreased tolerance of heat, tremor, palpitations, anxiety and nervousness. In some cases it can cause angina, chest pain, Diarrhea, diarrhoea, hair loss and muscle weakness. Such symptoms may be managed temporarily with drugs such as beta blockers. Long-term management of hyperthyroidism may include drugs that suppress thyroid function such as propylthiouracil, carbimazole and methimazole. Alternatively, Isotopes of iodine#Radioiodines 123I, 124I, 125I, and 131I in medicine and biology, radioactive iodine-131 can be used to destroy thyroid tissue: radioactive iodine is selectively taken up by thyroid cells, which over time destroys them. The chosen first-line treatment will depend on the individual and on the country where being treated. Thyroidectomy, Surgery to remove the thyroid can sometimes be performed as a Natural orifice transluminal endoscopic surgery#State of research, transoral thyroidectomy, a minimally invasive procedure. Surgery does however carry a risk of damage to the
parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...
s and the
recurrent laryngeal nerve The recurrent laryngeal nerve (RLN), also known as nervus recurrens, is a branch of the vagus nerve ( cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recur ...
, which innervates the vocal cords. If the entire thyroid gland is removed, hypothyroidism will inevitably result, and Thyroid hormone replacement, thyroid hormone substitutes will be needed.


Hypothyroidism

An underactive thyroid gland results in
hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
. Typical symptoms are abnormal weight gain, tiredness, constipation, heavy menstrual bleeding, hair loss, cold intolerance, and bradycardia, a slow heart rate. Iodine deficiency is the most common cause of hypothyroidism worldwide, and the autoimmune disease
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, Hashimoto's disease and autoimmune thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over ti ...
is the most common cause in the developed world. Other causes include congenital abnormalities, diseases causing transient inflammation, surgical removal or radioablation of the thyroid, the drugs amiodarone and lithium, amyloidosis, and sarcoidosis. Some forms of hypothyroidism can result in myxedema and severe cases can result in myxedema coma. Hypothyroidism is managed with replacement of the
thyroid hormones File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 ...
. This is usually given daily as an oral supplement, and may take a few weeks to become effective. Some causes of hypothyroidism, such as Postpartum thyroiditis and Subacute thyroiditis may be transient and pass over time, and other causes such as iodine deficiency may be able to be rectified with dietary supplementation.


Diseases


Graves' disease

Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...
is an autoimmune disorder that is the most common cause of hyperthyroidism. In Graves' disease, for an unknown reason autoantibody, autoantibodies develop against the thyroid stimulating hormone receptor. These antibodies activate the receptor, leading to development of a goitre and symptoms of hyperthyroidism, such as heat intolerance, weight loss, diarrhoea and palpitations. Occasionally such antibodies block but do not activate the receptor, leading to symptoms associated with hypothyroidism. In addition, gradual protrusion of the eyes may occur, called Graves' ophthalmopathy, as may swelling of the front of the shins. Graves' disease can be diagnosed by the presence of Pathognomonic, pathomnomonic features such as involvement of the eyes and shins, or isolation of autoantibodies, or by results of a radiolabelled uptake scan. Graves' disease is treated with anti-thyroid drugs such as propylthiouracil, which decrease the production of thyroid hormones, but hold a high rate of relapse. If there is no involvement of the eyes, then use of radioactive isotopes to ablate the gland may be considered. Surgical removal of the gland with subsequent thyroid hormone replacement may be considered, however this will not control symptoms associated with the eye or skin.


Nodules

Thyroid nodules are often found on the gland, with a prevalence of 4–7%. The majority of nodules do not cause any symptoms, thyroid hormone secretion is normal, and they are non-cancerous. Non-cancerous cases include simple cysts, colloid nodules, and thyroid adenomas. Malignant nodules, which only occur in about 5% of nodules, include Follicular thyroid cancer, follicular, Papillary thyroid cancer, papillary, Medullary thyroid cancer, medullary carcinomas and metastasis from other sites. Nodules are more likely in females, those who are exposed to radiation, and in those who are iodine deficient. When a nodule is present, thyroid function tests determine whether the nodule is secreting excess thyroid hormones, causing hyperthyroidism. When the thyroid function tests are normal, an medical ultrasound, ultrasound is often used to investigate the nodule, and provide information such as whether the nodule is fluid-filled or a solid mass, and whether the appearance is suggestive of a benign or malignant cancer. A needle aspiration biopsy may then be performed, and the sample undergoes cytology, in which the appearance of cells is viewed to determine whether they resemble normal or cancerous cells. The presence of multiple nodules is called a multinodular goitre; and if it is associated with hyperthyroidism, it is called a toxic multinodular goitre.


Goitre

An enlarged thyroid gland is called a
goitre A goitre (British English), or goiter (American English), is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are ...
. Goitres are present in some form in about 5% of people, and are the result of a large number of causes, including iodine deficiency, autoimmune disease (both Graves' disease and Hashimoto's thyroiditis), infection, inflammation, and infiltrative disease such as sarcoidosis and amyloidosis. Sometimes no cause can be found, a state called "simple goitre". Some forms of goitre are associated with pain, whereas many do not cause any symptoms. Enlarged goitres may extend beyond the normal position of the thyroid gland to below the sternum, around the airway or esophagus. Goitres may be associated with hyperthyroidism or hypothyroidism, relating to the underlying cause of the goitre. Thyroid function tests may be done to investigate the cause and effects of the goitre. The underlying cause of the goitre may be treated, however many goitres with no associated symptoms are Watchful waiting, simply monitored.


Inflammation

Inflammation of the thyroid is called thyroiditis, and may cause symptoms of hyperthyroidism or hypothyroidism. Two types of thyroiditis initially present with hyperthyroidism and are sometimes followed by a period of hypothyroidism – Hashimoto's thyroiditis and postpartum thyroiditis. There are other disorders that cause inflammation of the thyroid, and these include subacute thyroiditis, acute thyroiditis, silent thyroiditis, Riedel's thyroiditis and traumatic injury, including palpation thyroiditis.
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, Hashimoto's disease and autoimmune thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over ti ...
is an
autoimmune disorder An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...
in which the thyroid gland is infiltrated by the lymphocytes B cell and T cells. These progressively destroy the thyroid gland. In this way, Hasimoto's thyroiditis may have occurred insidiously, and only be noticed when thyroid hormone production decreases, causing symptoms of hypothyroidism. Hashimoto's is more common in females than males, much more common after the age of 60, and has known genetic risk factors. Also more common in individuals with Hashimoto's thyroiditis are Type 1 diabetes, pernicious anaemia, Addison's disease vitiligo. Postpartum thyroiditis occurs sometimes following childbirth. After delivery, the thyroid becomes inflamed and the condition initially presents with a period of hyperthyroidism followed by hypothyroidism and, usually, a return to normal function. The course of the illness takes place over several months, and is characterised by a painless goitre. Antibodies against thyroid peroxidase can be found on testing. The inflammation usually resolves without treatment, although thyroid hormone replacement may be needed during the period of hypothyroidism.


Cancer

The most common tumor affecting the thyroid is a benign thyroid adenoma, adenoma, usually presenting as a painless mass in the neck. Thyroid cancers are most often carcinomas, although cancer can occur in any tissue that the thyroid consists of, including cancer of C-cells and lymphomas. Cancers from other sites also rarely lodge in the thyroid. Radiation of the head and neck presents a Risk factor (epidemiology), risk factor for thyroid cancer, and cancer is more common in women than men, occurring at a rate of about 2:1. In most cases, thyroid cancer presents as a painless mass in the neck. It is very unusual for thyroid cancers to present with other symptoms, although in some cases cancer may cause hyperthyroidism. Most thyroid cancers are Papillary thyroid cancer, papillary, followed by Follicular thyroid cancer, follicular, Medullary thyroid cancer, medullary, and thyroid lymphoma. Because of the prominence of the thyroid gland, cancer is often detected earlier in the course of disease as the cause of a nodule, which may undergo fine-needle aspiration. Thyroid function tests will help reveal whether the nodule produces excess thyroid hormones. A radioactive iodine uptake test can help reveal the activity and location of the cancer and metastases. Thyroid cancers are treated by thyroidectomy, removing the whole or part of thyroid gland. Radioactive Iodine-131 may be given to Radiofrequency ablation, radioablate the thyroid. Thyroxine is given to replace the hormones lost and to suppress TSH production, as TSH may stimulate recurrence. With the exception of the rare anaplastic thyroid cancer, which carries a very poor prognosis, most thyroid cancers carry an excellent prognosis and can even be considered curable.


Congenital

A persistent thyroglossal duct is the most common clinically significant birth defect of the thyroid gland. A persistent sinus tract may remain as a vestigial remnant of the tubular development of the thyroid gland. Parts of this tube may be obliterated, leaving small segments to form thyroglossal cysts. Preterm neonates are at risk of hypothyroidism as their thyroid glands are insufficiently developed to meet their postnatal needs. In order to detect hypothyroidism in newborn babies, to prevent growth and development abnormalities in later life, many countries have newborn screening programs at birth. Infants with thyroid hormone deficiency (
congenital hypothyroidism Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with co ...
) can manifest problems of physical growth and development as well as brain development, termed cretinism. Children with congenital hypothyroidism are treated supplementally with levothyroxine, which facilitates normal growth and development. Mucinous, clear secretions may collect within these cysts to form either spherical masses or fusiform swellings, rarely larger than 2 to 3 cm in diameter. These are present in the midline of the neck anterior to the
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
. Segments of the duct and cysts that occur high in the neck are lined by stratified squamous epithelium, which is essentially identical to that covering the posterior portion of the tongue in the region of the foramen cecum. The disorders that occur in the lower neck more proximal to the thyroid gland are lined by epithelium resembling the thyroidal acinar epithelium. Characteristically, next to the lining epithelium, there is an intense lymphocytic infiltrate. superinfection, Superimposed infection may convert these lesions into abscess cavities, and rarely, give rise to cancers. Another disorder is that of thyroid dysgenesis which can result in various presentations of one or more ectopia (medicine), misplaced accessory thyroid glands. These can be asymptomatic.


Iodine

Iodine deficiency, most common in inland and mountainous areas, can predispose to goitre – if widespread, known as endemic goitre. Pregnant women deficient of iodine can give birth to infants with thyroid hormone deficiency. The use of iodised salt to add iodine to the diet has eliminated endemic cretinism in most developed countries, and over 120 countries have made the iodination of salt mandatory. Because the thyroid concentrates iodine, it also concentrates the various radioactive isotopes of iodine produced by nuclear fission. In the event of large accidental releases of such material into the environment, the uptake of radioactive iodine isotopes by the thyroid can, in theory, be blocked by saturating the uptake mechanism with a large surplus of Radiation pill, non-radioactive iodine, taken in the form of potassium iodide tablets. One consequence of the Chernobyl disaster was an increase in
thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, ...
s in children in the years following the accident. Excessive iodine intake is uncommon and usually has no effect on the thyroid function. Sometimes though it may cause hyperthyroidism, and sometimes hypothyroidism with a resulting goitre.


Evaluation

The thyroid is Medical examination, examined by observation of the gland and surrounding neck for swelling or enlargement. It is then palpation, felt, usually from behind, and a person is often asked to swallow to better feel the gland against the fingers of the examiner. The gland moves up and down with swallowing because of its attachments to the thyroid and cricoid cartilages. In a healthy person the gland is not visible yet is palpation, palpable as a soft mass. Examination of the thyroid gland includes the search for abnormal masses and the assessment of overall thyroid size. The character of the thyroid, swellings, nodules, and their consistency may all be able to be felt. If a goitre is present, an examiner may also feel down the neck consider Percussion (medicine), tapping the upper part of the chest to check for extension. Further tests may include raising the arms (Pemberton's sign), listening to the gland with a stethoscope for bruits, testing of reflexes, and palpation of the lymph nodes in the head and neck. An examination of the thyroid will also include observation of the person as a whole, to look for systemic signs such as weight gain or loss, hair loss, and signs in other locations – such as protrusion of the eyes or swelling of the calves in Graves' disease.


Tests

Thyroid function tests include a battery of blood tests, including the measurement of the thyroid hormones, as well as the measurement of thyroid stimulating hormone (TSH). They may reveal hyperthyroidism (high T3 and T4), hypothyroidism (low T3, T4), or subclinical hyperthyroidism (normal T3 and T4 with a low TSH). TSH levels are considered the most sensitive marker of thyroid dysfunction. They are however not always accurate, particularly if the cause of hypothyroidism is thought to be related to insufficient thyrotropin releasing hormone (TRH) secretion, in which case it may be low or falsely normal. In such a case a TRH stimulation test, in which TRH is given and TSH levels are measured at 30 and 60-minutes after, may be conducted. T3 and T4 can be measured directly. However, as the two thyroid hormones travel bound to other molecules, and it is the "free" component that is biologically active, free T3 and free T4 levels can be measured. T3 is preferred, because in hypothyroidism T3 levels may be normal. The ratio of bound to unbound thyroid hormones is known as the thyroid hormone binding ratio (THBR). It is also possible to measure directly the main carriers of the thyroid hormones, thyroglobulin and throxine-binding globulin. Thyroglobulin will also be measurable in a healthy thyroid, and will increase with inflammation, and may also be used to measure the success of thyroid removal or ablation. If successful, thyroglobulin should be undetectable. Lastly, antibodies against components of the thyroid, particularly anti-TPO and anti-thyroglobulin, can be measured. These may be present in normal individuals but are highly Psychic, sensitive for autoimmune-related disease.


Imaging

Ultrasound of the thyroid may be used to reveal whether structures are solid or filled with fluid, helping to differentiate between nodules and goitres and cysts. It may also help differentiate between malignant and benign lesions. When further imaging is required, a radiolabelled iodine-123 or technetium-99 uptake scan may take place. This can determine the size and shape of lesions, reveal whether nodules or goitres are metabolically active, and reveal and monitor sites of thyroid disease or cancer deposits metastases, outside the thyroid. A fine needle aspiration of a sample of thyroid tissue may be taken in order to evaluate a lesion seen on ultrasound which is then sent for histopathology and cytology. Computed tomography of the thyroid plays an important role in the evaluation of thyroid cancer.Creative Commons Attribution 4.0 International License
/ref> CT scans often Incidental imaging finding, incidentally find thyroid abnormalities, and thereby practically becomes the first investigation modality.


History

The thyroid gland received its modern name in the 1600s, when the anatomist Thomas Wharton (anatomist), Thomas Wharton likened its shape to that of an Ancient Greek shield or . However, the existence of the gland, and of the diseases associated with it, was known long before then.


Antiquity

The presence and diseases of the thyroid have been noted and treated for thousands of years. In 1600 BCE burnt sponge and seaweed (which contain iodine) were used within China for the treatment of goitres, a practice which has developed in many parts of the world. In Ayurveda, Ayurvedic medicine, the book Sushruta Samhita written about 1400 BCE described hyperthyroidism, hypothyroidism and goitre. Aristotle and Xenophon in the fifth century BCE describe cases of diffuse toxic goitre. Hippocrates and Plato in the fourth century BCE provided some of the first descriptions of the gland itself, proposing its function as a salivary gland. Pliny the Elder in the first century BCE referred to epidemics of goitre in the Alps and proposed treatment with burnt seaweed, a practice also referred to by Galen in the second century, referred to burnt sponge for the treatment of goitre. The Chinese language, Chinese pharmacological, pharmacology text ''Shennong Ben Cao Jing'', written ca. 200–250, also refers to goitre.


Scientific era

In 1500 polymath Leonardo da Vinci provided the first illustration of the thyroid. In 1543 anatomist Andreas Vesalius gave the first anatomic description and illustration of the gland. In 1656 the thyroid received its modern name, by the anatomist Thomas Wharton (anatomist), Thomas Wharton. The gland was named thyroid, meaning shield, as its shape resembled the shields commonly used in Ancient Greece. The English name ''thyroid gland'' is derived from the Contemporary Latin, medical Latin used by Wharton – . means 'gland' in Latin, and can be traced back to the Ancient Greek word , meaning 'shield-like/shield-shaped'. French chemist Bernard Courtois discovered iodine in 1811, and in 1896 Eugen Baumann documented it as the central ingredient in the thyroid gland. He did this by boiling the thyroid glands of a thousand sheep, and named the precipitate, a combination of the thyroid hormones, 'iodothyrin'. David Marine in 1907 proved that iodine is necessary for thyroid function. Graves' disease was described by Robert James Graves in 1834. The role of the thyroid gland in metabolism was demonstrated in 1895 by Adolf Magnus-Levy. Thyroxine was first isolated in 1914 and synthesized in 1927, and triiodothyroxine in 1952. The conversion of T4 to T3 was discovered in 1970. The process of discovering TSH took place over the early to mid twentieth century. TRH was discovered by Polish endocrinologist Andrew Schally in 1970, contributing in part to his Nobel Prize in Medicine in 1977. In the nineteenth century numerous authors described both cretinism and myxedema, and their relationship to the thyroid. Charles Mayo coined the term hyperthyroidism in 1910. Hakaru Hashimoto documented a case of Hashimoto's thyroiditis in 1912, autoantibody, antibodies in this disease were demonstrated in 1956. Knowledge of the thyroid and its conditions developed throughout the late nineteenth and twentieth centuries, with many modern treatments and investigative modalities evolving throughout the mid twentieth century, including the use of radioactive iodine, thiouracil and fine needle aspiration.


Surgery

Either Aëtius of Amida, Aetius in the sixth century CE or Persian Ali ibn Abbas al-Magusi in 990 CE conducted the first recorded thyroidectomy as a treatment for goitre. Operations remained risky and generally were not successful until the 19th century, when descriptions emerged from a number of authors including Prussian surgeon Theodor Billroth, Swiss surgeon and physiologist Theodor Kocher, American physician Charles Horace Mayo, Charles Mayo, American surgeons William Halsted and George Washington Crile, George Crile. These descriptions provided the basis for modern thyroid surgery. Theodor Kocher went on to win the Nobel Prize in Physiology or Medicine in 1909 "for his work on the physiology, pathology and surgery of the thyroid gland".


Other animals

The thyroid gland is found in all vertebrates. In fish, it is usually located below the gills and is not always divided into distinct lobes. However, in some teleosts, patches of thyroid tissue are found elsewhere in the body, associated with the kidneys, spleen, heart, or eyes. In tetrapods, the thyroid is always found somewhere in the neck region. In most tetrapod species, there are two paired thyroid glands – that is, the right and left lobes are not joined. However, there is only ever a single thyroid gland in most mammals, and the shape found in humans is common to many other species. In larval lampreys, the thyroid originates as an exocrine gland, secreting its hormones into the gut, and associated with the larva's filter-feeding apparatus. In the adult lamprey, the gland separates from the gut, and becomes endocrine, but this path of development may reflect the evolutionary origin of the thyroid. For instance, the closest living relatives of vertebrates, the tunicates and amphioxi (lancelets), have a structure very similar to that of larval lampreys (the endostyle), and this also secretes iodine-containing compounds, though not thyroxine. Thyroxine is critical to metabolic regulation, and growth throughout the vertebrate clade. Iodine and T4 trigger the metamorphosis, change from a plant-eating water-dwelling tadpole into a meat-eating land-dwelling frog, with better neurological, visuospatial, smell and cognitive abilities for hunting, as seen in other predatory animals. A similar phenomenon happens in the neotenic amphibian salamanders, which, without introducing iodine, do not transform into land-dwelling adults, and live and reproduce in the larval form of aquatic axolotl. Among amphibians, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; in contrast, administering thyroxine will trigger metamorphosis. In amphibian metamorphosis, thyroxine and iodine also exert a well-studied experimental model of apoptosis on the cells of gills, tail, and fins of tadpoles. Iodine, via iodolipids, has favored the evolution of terrestrial animal species and has likely played a crucial role in the evolution of the human brain.


See also

* Desiccated thyroid * Thyroid disease in pregnancy


References


Books

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External links


Endocrine Web: Thyroid
{{Authority control Thyroid, Glands Endocrine system anatomy Human head and neck