Thyroid
Encyclopedia
The thyroid gland or simply, the thyroid (ˈθaɪrɔɪd ...), in vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

 anatomy
Anatomy
Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...

, is one of the largest endocrine glands. The thyroid gland is found in the neck
Neck
The neck is the part of the body, on many terrestrial or secondarily aquatic vertebrates, that distinguishes the head from the torso or trunk. The adjective signifying "of the neck" is cervical .-Boner anatomy: The cervical spine:The cervical portion of the human spine comprises seven boney...

, below (inferior to) the thyroid cartilage
Thyroid cartilage
The thyroid cartilage is the largest of the nine cartilages that make up the laryngeal skeleton, the cartilage structure in and around the trachea that contains the larynx....

 (which 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 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s, and controls how sensitive the body is to other hormones. It participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....

 (T3) and thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 (T4). These hormones regulate the rate of metabolism
Basal metabolic rate
Basal Metabolic Rate , and the closely related resting metabolic rate , is the amount of daily energy expended by humans and other animals at rest. Rest is defined as existing in a neutrally temperate environment while in the post-absorptive state...

 and affect the growth and rate of function of many other systems in the body. T3 and T4 are synthesized from both iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

 and tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

. The thyroid also produces calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

, which plays a role in calcium homeostasis.

Hormonal output from the thyroid is regulated by thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 (TSH) produced by the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...

, which itself is regulated by thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

 (TRH) produced by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

.

The thyroid gets its name from the Greek word for "shield", due to the shape of the related thyroid cartilage. The most common problems of the thyroid gland consist of an overactive thyroid gland, referred to as hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

, and an underactive thyroid gland, referred to as hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

.

Anatomy

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
Thyroid isthmus
The thyroid isthmus connects together the lower thirds of the lobes; it measures about 1.25 cm. in breadth, and the same in depth, and usually covers the second and third rings of the trachea.Its situation and size present, however, many variations....

. The organ is situated on the anterior side of the neck, lying against and around the larynx
Larynx
The larynx , commonly called the voice box, is an organ in the neck of amphibians, reptiles and mammals involved in breathing, sound production, and protecting the trachea against food aspiration. It manipulates pitch and volume...

 and trachea
Vertebrate trachea
In tetrapod anatomy the trachea, or windpipe, is a tube that connects the pharynx or larynx to the lungs, allowing the passage of air. It is lined with pseudostratified ciliated columnar epithelium cells with goblet cells that produce mucus...

, reaching posteriorly the oesophagus and carotid sheath
Carotid sheath
The carotid sheath is an anatomical term for the fibrous connective tissue that surrounds the vascular compartment of the neck. It is part of the deep cervical fascia of the neck, below the superficial cervical fascia meaning the subcutaneous adipose tissue immediately beneath the skin.The deep...

. It starts cranially at the oblique line on the thyroid cartilage
Thyroid cartilage
The thyroid cartilage is the largest of the nine cartilages that make up the laryngeal skeleton, the cartilage structure in and around the trachea that contains the larynx....

 (just below the laryngeal prominence, or 'Adam's Apple
Adam's apple
The laryngeal prominence—commonly known as the Adam's Apple—is a feature of the human neck. This lump, or protrusion, is formed by the angle of the thyroid cartilage surrounding the larynx...

'), 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 position in relation to these during swallowing.

The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroidea, composed of an internal and external layer. The external layer is anteriorly continuous with the lamina pretrachealis fasciae cervicalis
Pretracheal fascia
The pretracheal fascia extends medially in front of the carotid vessels, and assists in forming the carotid sheath.It is continued behind the depressor muscles of the hyoid bone, and, after enveloping the thyroid gland, is prolonged in front of the trachea to meet the corresponding layer of the...

and posteriorolaterally continuous with the carotid sheath. The gland is covered anteriorly with infrahyoid muscles and laterally with the sternocleidomastoid muscle
Sternocleidomastoid muscle
In human anatomy, the sternocleidomastoid muscle , also known as sternomastoid and commonly abbreviated as SCM, is a paired muscle in the superficial layers of the anterior portion of the neck...

 also known as sternomastoid muscle. On the posterior side, the gland is fixed to the cricoid
Cricoid
The cricoid cartilage, or simply cricoid , is the only complete ring of cartilage around the trachea.-Location:...

 and tracheal cartilage and cricopharyngeus muscle by a thickening of the fascia to form the posterior suspensory ligament of Berry. The thyroid gland's firm attachment to the underlying trachea is the reason behind its movement with swallowing. In variable extent, Lalouette's Pyramid
Lalouette's Pyramid
Lalouette's pyramid is a pyramidal extension of the thyroid gland, described by Pierre Lalouette in 1743.Lalouette's pyramid is seldom present in representations of the thyroid....

, a pyramidal extension of the thyroid lobe, is present at the most anterior side of the lobe. In this region, the recurrent laryngeal nerve
Recurrent laryngeal nerve
The recurrent laryngeal nerve is a branch of the vagus nerve that supplies motor function and sensation to the larynx . It travels within the endoneurium...

 and the inferior thyroid artery pass next to or in the ligament and tubercle.

Between the two layers of the capsule and on the posterior side of the lobes, there are on each side two parathyroid gland
Parathyroid gland
The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...

s.

The thyroid isthmus is variable in presence and size, can change shape and size, and can encompass a cranially extending pyramid lobe (lobus pyramidalis or processus pyramidalis), remnant of the thyroglossal duct
Thyroglossal duct
The thyroglossal duct is an embryological anatomical structure forming an open connection between the initial area of development of the thyroid gland and its final position....

. The thyroid is one of the larger endocrine glands, weighing 2-3 grams in neonates and 18-60 grams in adults, and is increased in pregnancy.

The thyroid is supplied with arterial blood from the superior thyroid artery
Superior thyroid artery
The superior thyroid artery arises from the external carotid artery just below the level of the greater cornu of the hyoid bone and ends in the thyroid gland.-Relations:...

, a branch of the external carotid artery
External carotid artery
In human anatomy, the external carotid artery is a major artery of the head and neck. It arises from the common carotid artery when it bifurcates into the external and internal carotid artery.-Course:...

, and the inferior thyroid artery
Inferior thyroid artery
The inferior thyroid artery arrises from the thyrocervical trunk and passes upward, in front of the vertebral artery and Longus colli, then turns medially behind the carotid sheath and its contents, and also behind the sympathetic trunk, the middle cervical ganglion resting upon the...

, a branch of the thyrocervical trunk
Thyrocervical trunk
The thyrocervical trunk is a branch of the subclavian artery arising from the first portion of this vessel, i.e. between the origin of the subclavian artery and the inner border of the scalenus anterior muscle...

, and sometimes by the thyroid ima artery
Thyroid ima artery
The thyroidea ima ascends in front of the trachea to the lower part of the thyroid gland, which it supplies.It varies greatly in size, and appears to compensate for deficiency or absence of one of the other thyroid vessels...

, branching directly from the brachiocephalic trunk. The venous blood is drained via superior thyroid vein
Superior thyroid vein
The superior thyroid vein begins in the substance and on the surface of the thyroid gland, by tributaries corresponding with the branches of the superior thyroid artery, and ends in the upper part of the internal jugular vein....

s, draining in the internal jugular vein
Internal jugular vein
The two internal jugular veins collect the blood from the brain, the superficial parts of the face, and the neck.-Path:On both sides and at the base of the brain, the inferior petrosal sinus and the sigmoid sinus join to form the internal jugular vein...

, and via inferior thyroid veins, draining via the plexus thyroideus impar in the left brachiocephalic vein
Brachiocephalic vein
The left and right brachiocephalic veins in the upper chest are formed by the union of each corresponding internal jugular vein and subclavian vein...

.

Lymphatic drainage passes frequently the lateral deep cervical lymph nodes
Cervical lymph nodes
Cervical lymph nodes are lymph nodes found in the neck.-Classification:There are approximately 300 lymph nodes in the neck, and they can be classified in many different ways.Henri Rouvière produced an influential classification in 1938...

 and the pre- and parathracheal lymph nodes
Cervical lymph nodes
Cervical lymph nodes are lymph nodes found in the neck.-Classification:There are approximately 300 lymph nodes in the neck, and they can be classified in many different ways.Henri Rouvière produced an influential classification in 1938...

. The gland is supplied by parasympathetic nerve input from the superior laryngeal nerve
Superior laryngeal nerve
The superior laryngeal nerve is a branch of the vagus nerve. It arises from the middle of the ganglion nodosum and in its course receives a branch from the superior cervical ganglion of the sympathetic....

 and the recurrent laryngeal nerve
Recurrent laryngeal nerve
The recurrent laryngeal nerve is a branch of the vagus nerve that supplies motor function and sensation to the larynx . It travels within the endoneurium...

.

Evolution

Phylogenetically, thyroid cells are derived from primitive iodide-concentrating gastroenteric cells. Given the essential nature of iodine compounds in living organisms, organisms moving from iodine-rich seas to iodine-deficient land needed stronger systems for uptake and storage of that element. The thyroid appears to have evolved to serve that need. Venturi et al. suggested that iodide
Iodide
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. This page is for the iodide ion and its salts. For information on organoiodides, see organohalides. In everyday life, iodide is most commonly encountered as a component of iodized salt,...

 has an ancestral antioxidant function in all iodide-concentrating cells from primitive algae to more recent vertebrates. In 2008, this ancestral antioxidant action of iodides has been experimentally confirmed by Küpper et al. Thyroxine has a 700 million year history. It is present, while showing no hormonal action, in the fibrous exoskeletal scleroproteins of the lowest invertebrates, Porifera and Anthozoa
Anthozoa
Anthozoa is a class within the phylum Cnidaria that contains the sea anemones and corals. Unlike other cnidarians, anthozoans do not have a medusa stage in their development. Instead, they release sperm and eggs that form a planula, which attaches to some substrate on which the cnidarian grows...

. The active hormone, triiodothyronine (T3), became active in metamorphosis and thermogenesis
Thermogenesis
Thermogenesis is the process of heat production in organisms. It occurs mostly in warm-blooded animals, but a few species of thermogenic plants exist.-Types:...

, allowing for better adaptation of organisms to terrestrial environment (fresh water, atmosphere, gravity, temperature and diet).

Embryological development

In the fetus, at 3–4 weeks of gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue between the tuberculum impar
Tuberculum impar
During the third week of embryological development there appears, immediately behind the ventral ends of the two halves of the mandibular arch, a rounded swelling named the tuberculum impar, which was described by His as undergoing enlargement to form the buccal part of the tongue.More recent...

 and the copula linguae
Copula linguae
Also known as the hypobranchial eminence.The furcula is at first separated from the tuberculum impar by a depression, but later by a ridge, the copula, formed by the forward growth and fusion of the ventral ends of the second, third, and part of the fourth branchial arches....

 at a point later indicated by the foramen cecum
Foramen cecum (tongue)
The dorsum of the tongue is convex and marked by a median sulcus, which divides it into symmetrical halves; this sulcus ends behind, about 2.5 cm from the root of the organ, in a depression, the foramen cecum , from which a shallow groove, the sulcus terminalis, runs lateral and anterior on either...

. The thyroid then descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct
Thyroglossal duct
The thyroglossal duct is an embryological anatomical structure forming an open connection between the initial area of development of the thyroid gland and its final position....

. Over the next few weeks, it migrates to the base of the neck, passing anterior to the hyoid bone. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct.

Thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

 (TRH) and thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 (TSH) start being secreted from the fetal hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 and pituitary at 18-20 weeks of gestation, and fetal production of thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 (T4) reach a clinically significant level at 18–20 weeks. Fetal triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....

 (T3) remains low (less than 15 ng/dL) until 30 weeks of gestation, and increases to 50 ng/dL at term. Fetal self-sufficiency of thyroid hormones protects the fetus against e.g. brain development abnormalities caused by maternal hypothyroidism. However, preterm births can suffer neurodevelopmental disorders due to lack of maternal thyroid hormones due their own thyroid being insufficiently developed to meet their postnatal needs.

The portion of the thyroid containing the parafollicular C cells, those responsible for the production of calcitonin, are derived from the neural crest
Neural crest
Neural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....

. This is first seen as the ultimobranchial body
Ultimobranchial body
The ultimopharyngeal body or ultimobranchial body or ultimobranchial gland is a small organ found in the neck region of many animals....

, which joins the primordial thyroid gland during its descent to its final location in the anterior neck.

Aberrations in embryological development can cause various forms of thyroid dysgenesis
Thyroid dysgenesis
Thyroid agenesis is a cause of congenital hypothyroidism where the thyroid is missing, ectopic, or severely underdeveloped....

.

Histology

At the microscopic level, there are three primary features of the thyroid:
Feature Description
>-
| Follicles
iodide
Iodide
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. This page is for the iodide ion and its salts. For information on organoiodides, see organohalides. In everyday life, iodide is most commonly encountered as a component of iodized salt,...

 ions, I-) from the blood for production of thyroid hormones, but also for storage of iodine in thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

, in fact iodine is necessary for other important iodine-concentrating organs as breast, stomach, salivary glands, thymus etc. (see iodine in biology
Iodine in biology
Iodine is an essential trace element for life, the heaviest element commonly needed by living organisms, and the second-heaviest known to be used by any form of life .-The thyroid:Iodine's main role in animal biology is as constituents of the thyroid hormones, thyroxine and...

).
Twenty-five percent of all the body's iodide ions are in the thyroid gland. Inside the follicles, colloid serves as a reservoir of materials for thyroid hormone production and, to a lesser extent, acts as a reservoir for the hormones themselves. Colloid is rich in a protein called thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

.
>-
| Thyroid epithelial cells
Thyroid epithelial cell
Thyroid epithelial cells are cells in the thyroid gland that are responsible for the production and secretion of thyroid hormones, that is, thyroxine and triiodothyronine .-Function:...


(or "follicular cells")
T3
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....

 and T4
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

. When the gland is not secreting T3/T4 (inactive), the epithelial cells range from low columnar to cuboidal cells. When active, the epithelial cells become tall columnar cells.
>-
| Parafollicular cell
Parafollicular cell
Parafollicular cells are cells in the thyroid that produce and secrete calcitonin. They are located adjacent to the thyroid follicles and reside in the connective tissue. These cells are large and have a pale stain compared with the follicular cells or colloid...

s
(or "C cells")
Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells, which secrete calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

.

Disorders

Thyroid disorders include hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

 (abnormally increased activity), hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

 (abnormally decreased activity) and thyroid nodule
Thyroid nodule
Thyroid nodules are lumps which commonly arise within an otherwise normal thyroid gland. They indicate a thyroid neoplasm, but only a small percentage of these are thyroid cancers.-Presentation:...

s, which are generally benign thyroid neoplasms, but may be thyroid cancer
Thyroid cancer
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...

s. All these disorders may give rise to goiter, that is, an enlarged thyroid.

Hyperthyroidism

Hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

, or overactive thyroid, is the overproduction of the thyroid hormones T3 and T4, and is most commonly caused by the development of Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

, an autoimmune disease in which antibodies are produced which stimulate the thyroid to secrete excessive quantities of thyroid hormones. The disease can result in the formation of a toxic goiter as a result of thyroid growth in response to a lack of negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

 mechanisms. It presents with symptoms such as a thyroid goiter, protruding eyes (exopthalmos), palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

s, excess sweating, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

, muscle weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...

 and unusual sensitivity to heat. The appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

 is often increased.

Beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...

s are used to decrease symptoms of hyperthyroidism such as increased heart rate
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

s, anxiety and heart palpitations, and anti-thyroid drugs are used to decrease the production of thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...

s, in particular, in the case of Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

. These medications take several months to take full effect and have side-effects
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

 such as skin rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...

 or a drop in white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

 count, which decreases the ability of the body to fight off infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s. These drugs involve frequent dosing (often one pill every 8 hours) and often require frequent doctor visits and blood tests to monitor the treatment, and may sometimes lose effectiveness over time. Due to the side-effects and inconvenience of such drug regimens, some patients choose to undergo radioactive iodine-131
Iodine-131
Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical...

 treatment. Radioactive iodine is administered in order to destroy a proportion of or the entire thyroid gland, since the radioactive iodine is selectively taken up by the gland and gradually destroys the cells of the gland. Alternatively, the gland may be partially or entirely removed surgically
Thyroidectomy
A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland...

, though iodine treatment is usually preferred since the surgery is invasive
Invasiveness of surgical procedures
There are three main categories which describe the invasiveness of surgical procedures. These are: non-invasive procedures, minimally invasive procedures, and invasive procedures ....

 and carries a risk of damage to the parathyroid glands or the nerves controlling the vocal cords
Vocal folds
The vocal folds, also known commonly as vocal cords, are composed of twin infoldings of mucous membrane stretched horizontally across the larynx...

. If the entire thyroid gland is removed, hypothyroidism results.

Hypothyroidism

Hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

 is the underproduction of the thyroid hormones T3 and T4. Hypothyroid disorders may occur as a result of congenital thyroid abnormalities (see congenital hypothyroidism
Congenital hypothyroidism
Congenital hypothyroidism is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more have mild or partial degrees. If untreated for several months after birth, severe congenital hypothyroidism...

), autoimmune disorders such as Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

, iodine deficiency
Iodine deficiency
Iodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inlandareas where no marine foods are eaten—iodine deficiency gives rise to...

 (more likely in poorer countries) or the removal of the thyroid following surgery to treat severe hyperthyroidism and/or thyroid cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. Typical symptoms are abnormal weight gain, tiredness, baldness, cold intolerance, and bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

. Hypothyroidism is treated with hormone replacement therapy
Hormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...

, such as levothyroxine
Levothyroxine
Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...

, which is typically required for the rest of the patient's life. Thyroid hormone treatment is given under the care of a physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...

 and may take a few weeks to become effective.

Negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

 mechanisms result in growth of the thyroid gland when thyroid hormones are being produced in sufficiently low quantities as a means of increasing the thyroid output; however, where the hypothyroidism is caused by iodine insufficiency, the thyroid is unable to produce T3 and T4 and as a result, the thyroid may continue to grow to form a non-toxic goiter. It is termed non-toxic as it does not produce toxic quantities of thyroid hormones, despite its size.

Initial hyperthyroidism followed by hypothyroidism

This is the overproduction of T3 and T4 followed by the underproduction of T3 and T4. There are two types: Hashimoto's thyroiditis and postpartum thyroiditis.

Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

 or Hashimoto's Disease is an autoimmune
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

 disorder whereby the body's own immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 reacts with the thyroid tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 in an attempt to destroy it. At the beginning, the gland may be overactive, and then becomes underactive as the gland
Gland
A gland is an organ in an animal's body that synthesizes a substance for release of substances such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...

 is damaged resulting in too little thyroid hormone production or hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

. Some patients may experience "swings" in hormone levels that can progress rapidly from hyper-to-hypothyroid (sometimes mistaken as severe moodswings, or even being bipolar
Bipolar
-Medicine:* Bipolar cell* Bipolar cell of the retina* Bipolar disorder** Bipolar I disorder** Bipolar II disorder** Bipolar NOS* Bipolar spectrum-Astronomy:* Bipolar nebula, a two-lobed, axially symmetric nebula...

, before the proper clinical diagnosis is made). Some patients may experience these "swings" over a longer period of time, over days or weeks or even months. Hashimoto's is more common in females than males, usually appearing after the age of 30, and tends to run in families meaning it can be seen as a genetic disease. Also more common in individuals with Hashimoto's Thyroiditis are type 1 diabetes
Diabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...

 and celiac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...

.

Postpartum thyroiditis
Postpartum thyroiditis
Postpartum thyroiditis is a phenomenon observed following pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. It affects about 5% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal...

 occurs in some females following the birth of a child. After delivery, the gland becomes inflamed and the condition initially presents with overactivity of the gland followed by underactivity. In some cases, the gland may recover with time and resume its functions. In others it may not. The etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....

 is not always known, but can sometimes be attributed to autoimmunity, such as Hashimoto's Thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

 or Graves' Disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

.

Cancers

Cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s do occur in the thyroid gland and are more common in females. In most cases, the thyroid cancer presents as a painless mass in the neck. It is very unusual for the thyroid cancers to present with symptoms, unless it has been neglected. One may be able to feel a hard nodule in the neck. Diagnosis is made using a needle biopsy and various radiological studies.

Non-cancerous nodules

Many individuals may find the presence of thyroid nodule
Thyroid nodule
Thyroid nodules are lumps which commonly arise within an otherwise normal thyroid gland. They indicate a thyroid neoplasm, but only a small percentage of these are thyroid cancers.-Presentation:...

s in the neck. The majority of these thyroid nodules are benign
Benignity
Benignity [from Latin benignus , from bonus + genus ] is a medical term used to describe a condition that is harmless...

 (non cancerous). The presence of a thyroid nodule does not mean that one has thyroid disease. Most thyroid nodules do not cause any symptoms, and most are discovered on an incidental examination. Doctors usually perform a needle aspiration biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...

 of the thyroid to determine the status of the nodules. If the nodule is found to be non-cancerous, no other treatment is required. If the nodule is suspicious then surgery is recommended..

Congenital anomalies

A persistent thyroglossal duct
Persistent thyroglossal duct
A persistent thyroglossal duct is a usually benign medical condition in which the thyroglossal duct, a structure usually only found during embryonic development, fails to atrophy...

 or cyst is the most common clinically significant congenital anomaly 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 cysts
Thyroglossal cyst
A thyroglossal cyst is a fibrous cyst that forms from a persistent thyroglossal duct.-Presentation:It usually presents as a midline neck lump that is usually painless, smooth and cystic, if infected pain can occur...

. These occur at any age and might not become evident until adult life. 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
Neck
The neck is the part of the body, on many terrestrial or secondarily aquatic vertebrates, that distinguishes the head from the torso or trunk. The adjective signifying "of the neck" is cervical .-Boner anatomy: The cervical spine:The cervical portion of the human spine comprises seven boney...

 anterior to the trachea
Trachea
Trachea may refer to:* Vertebrate trachea, or windpipe, in terrestrial vertebrates, such as birds and mammals* Invertebrate trachea, in terrestrial invertebrates, such as insects and crustaceans* Vessel elements in plants...

. Segements of the duct and cysts that occur high in the neck are lined by stratified squamous epithelium
Stratified squamous epithelium
A stratified squamous epithelium consists of squamous epithelial cells arranged in layers upon a basement membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural integrity...

, which is essentially identical to that covering the posterior portion of the tongue
Tongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...

 in the region of the foreamen cecum. The anomalies that occur in the lower neck more proximal to the thyroid gland are lined by epithelium resembling the thyroidal acinar epithelium. Charcteristically, next to the lining epithelium, there is an intense lymphocytic inflitrate. Superimposed infection may convert these lesions into abscess cavities, and rarely, give rise to cancers.

Other disorders

  • Limited research shows that seasonal allergies
    Allergic rhinitis
    Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...

     may trigger episodes of hypo- or hyperthyroidism.
  • A ectopic thyroid is an entire or parts of the thyroid located in another part of the body than what is the usual case.

Physiology

The primary function of the thyroid is production of the hormones triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....

 (T3), thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 (T4), and calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 and spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

. T3 is several times more powerful than T4, which is largely a prohormone
Prohormone
A prohormone is a substance that is a precursor to a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. The primary function of a prohormone is to enhance the strength of the hormone that already occurs in the...

, perhaps four or even ten times more active.

T3 and T4 production and action

Thyroxine (T4) is synthesised by the follicular cells
Thyroid epithelial cell
Thyroid epithelial cells are cells in the thyroid gland that are responsible for the production and secretion of thyroid hormones, that is, thyroxine and triiodothyronine .-Function:...

 from free tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 and on the tyrosine residues of the protein called thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

 (Tg). Iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

 is captured with the "iodine trap" by the hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

 generated by the enzyme thyroid peroxidase
Thyroid peroxidase
Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...

 (TPO) and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on Tg, and on free tyrosine. Upon stimulation by the thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 (TSH), the follicular cells reabsorb Tg and cleave the iodinated tyrosines from Tg in lysosomes, forming T4 and T3 (in T3, one iodine atom is absent compared to T4), and releasing them into the blood. Deiodinase enzymes
Deiodinase
Iodothyronine deiodinases are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine , the precursor of 3,5,3’-triiodothyronine is transformed into T3 by deiodinase activity. T3, through binding a nuclear thyroid hormone receptor,...

 convert T4 to T3. Thyroid hormone secreted from the gland is about 80-90% T4 and about 10-20% T3.

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. A transport protein that seems to be important for T4 transport across the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

 (OATP1C1) has been identified. A second transport protein (MCT8) is important for T3 transport across brain cell membranes.

Non-genomic actions of T4 are those that are not initiated by liganding of the hormone to intranuclear thyroid receptor. These may begin at the plasma membrane or within cytoplasm. Plasma membrane-initiated actions begin at a receptor on the integrin alphaV beta3 that activates ERK1/2. This binding culminates in local membrane actions on ion transport systems such as the Na(+)/H(+) exchanger or complex cellular events including cell proliferation. These integrins are concentrated on cells of the vasculature and on some types of tumor cells, which in part explains the proangiogenic effects of iodothyronines and proliferative actions of thyroid hormone on some cancers including gliomas. T4 also acts on the mitochondrial genome via imported isoforms of nuclear thyroid receptors to affect several mitochondrial transcription factors. Regulation of actin polymerization by T4 is critical to cell migration in neurons and glial cells and is important to brain development.

T3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytoplasmic in origin or may begin at integrin alpha V beta3.

In the blood, T4 and T3 are partially bound to thyroxine-binding globulin
Thyroxine-binding globulin
Thyroxine-binding globulin binds thyroid hormone in circulation. It is one of three proteins responsible for carrying the thyroid hormones thyroxine and 3,5,3’-triiodothyronine in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest...

 (TBG), transthyretin
Transthyretin
Transthyretin is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine and retinol binding protein bound to retinol. This is how transthyretin gained its name, transports thyroxine and retinol...

, and albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...

. Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity. As with the steroid hormone
Steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

s and retinoic acid
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....

, thyroid hormones cross the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 and bind to intracellular receptor
Intracellular receptor
Intracellular receptors are receptors located inside the cell rather than on its cell membrane. Examples are the class of nuclear receptors located in the cell nucleus and the IP3 receptor located on the endoplasmic reticulum...

s (α1, α2, β1 and β2), which act alone, in pairs or together with the retinoid X-receptor as transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

s to modulate DNA transcriptionhttp://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/receptors.html.

T3 and T4 regulation

The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH), released by the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...

. The thyroid and thyrotrope
Thyrotrope
Thyrotropes are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone in response to thyrotropin releasing hormone .Thyrotropes appear basophilic in histological preparations....

s form a negative feedback loop
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

: TSH production is suppressed when the T4 levels are high. The TSH production itself is modulated by thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

 (TRH), which is produced by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 and secreted at an increased rate in situations such as cold exposure (to stimulate thermogenesis
Thermogenesis
Thermogenesis is the process of heat production in organisms. It occurs mostly in warm-blooded animals, but a few species of thermogenic plants exist.-Types:...

). TSH production is blunted by somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...

 (SRIH), rising levels of glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

s and sex hormones (estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

 and testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

), and excessively high blood iodide concentration.

An additional hormone produced by the thyroid contributes to the regulation of blood calcium
Calcium metabolism
Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcemia or hypocalcemia, both of which can have important consequences for health....

 levels. Parafollicular cells produce calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

 in response to hypercalcemia. Calcitonin stimulates movement of calcium into bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

, in opposition to the effects of parathyroid hormone
Parathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

 (PTH). However, calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid (thyroidectomy
Thyroidectomy
A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland...

), but not the parathyroids.

Thyroid function tests

Test Abbreviation >-
| Serum thyrotropin/thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

TSH 0.3–3.0 μU/ml
>-
| Free thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

FT4 | 7–18 ng/l = 0.7–1.8 ng/dl
|-
| Serum triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....

T3 0.8–1.8 μg/l = 80–180 ng/dl
>-
| Radioactive iodine-123
Iodine-123
Iodine-123 is a radioactive isotope of iodine used in nuclear medicine imaging, including single photon emission computed tomography . The isotope's half-life is 13.22 hours; the decay by electron capture to tellurium-123 emits gamma radiation with predominant energies of 159 keV and 127 keV...

 uptake
RAIU 10–30%
>-
| Radioiodine scan (gamma camera)
N/A >-
| Free thyroxine fraction
FT4F >-
| Serum thyroxine
T4 >-
| Thyroid hormone binding ratio
THBR >-
| Free thyroxine index
FT4I >-
| Free triiodothyronine l
FT3 >-
| Free T3 Index
FT3I >-
| Thyroxine-binding globulin
TBG  >-
| TRH stimulation test
Peak TSH >-
| Serum thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

 l
Tg >-
| Thyroid microsomal antibody titer
TMAb >-
| Thyroglobulin antibody titer
TgAb


Significance of iodine

In areas of the world where iodine is lacking in the diet the thyroid gland can become considerably enlarged, a condition called endemic goiter. Pregnant women on a diet that is severely deficient of iodine can give birth to infants who can present with thyroid hormone deficiency (congenital hypothyroidism
Congenital hypothyroidism
Congenital hypothyroidism is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more have mild or partial degrees. If untreated for several months after birth, severe congenital hypothyroidism...

), manifesting in problems of physical growth and development as well as brain development (a condition referred to as endemic cretinism
Cretinism
Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones usually due to maternal hypothyroidism.-Etymology and use of cretin:...

). In many developed countries, newborns are routinely tested for congenital hypothyroidism as part of newborn screening
Newborn screening
Newborn screening is the process by which infants are screened shortly after birth for a list of disorders that are treatable, but difficult or impossible to detect clinically. Screening programs are often run by state or national governing bodies with the goal of screening all infants born in the...

. Children with congenital hypothyroidism are treated supplementally with levothyroxine
Levothyroxine
Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...

, which facilitates normal growth and development.

Thyroxine is critical to the regulation of metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil
Propylthiouracil
Propylthiouracil or 6-n-Propylthiouracil is a thioamide drug used to treat hyperthyroidism by decreasing the amount of thyroid hormone produced by the thyroid gland...

 (PTU) can prevent tadpole
Tadpole
A tadpole or polliwog is the wholly aquatic larval stage in the life cycle of an amphibian, particularly that of a frog or toad.- Appellation :...

s from metamorphosing into frogs; in contrast, administering thyroxine will trigger metamorphosis.

Because the thyroid concentrates this element, it also concentrates the various radioactive isotope
Isotope
Isotopes are variants of atoms of a particular chemical element, which have differing numbers of neutrons. Atoms of a particular element by definition must contain the same number of protons but may have a distinct number of neutrons which differs from atom to atom, without changing the designation...

s of iodine produced by nuclear fission
Nuclear fission
In nuclear physics and nuclear chemistry, nuclear fission is a nuclear reaction in which the nucleus of an atom splits into smaller parts , often producing free neutrons and photons , and releasing a tremendous amount of energy...

. 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 non-radioactive iodine, taken in the form of potassium iodide tablets. One consequence of the Chernobyl disaster
Chernobyl disaster
The Chernobyl disaster was a nuclear accident that occurred on 26 April 1986 at the Chernobyl Nuclear Power Plant in Ukraine , which was under the direct jurisdiction of the central authorities in Moscow...

 was an increase in thyroid cancer
Thyroid cancer
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...

s in children in the years following the accident.

The use of iodised salt
Iodised salt
Iodised salt is table salt mixed with a minute amount of various iodine-containing salts. The ingestion of iodide prevents iodine deficiency. Worldwide, iodine deficiency affects about two billion people and is the leading preventable cause of mental retardation. It also causes thyroid gland...

 is an efficient way to add iodine to the diet. It has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour, cooking oil, and salt mandatory. Potassium iodide and sodium iodide are typically used forms of supplemental iodine.

As with most substances, either too much or too little can cause problems. Recent studies on some populations are showing that excess iodine intake could cause an increased prevelence of autoimmune thyroid disease
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

, resulting in permanent hypothyroidism.

History

There are several findings that evidence a great interest for thyroid disorders just in the Medieval Medical School of Salerno
Salerno
Salerno is a city and comune in Campania and is the capital of the province of the same name. It is located on the Gulf of Salerno on the Tyrrhenian Sea....

 (12th century). Rogerius Salernitanus
Rogerius (physician)
Rogerius , also called Rogerius Salernitanus, Roger Frugard, Roger Frugardi, Roggerio Frugardo, Rüdiger Frutgard and Roggerio dei Frugardi, was a Salernitan surgeon who wrote a work on medicine entitled Practica Chirurgiae around 1180...

, the Salernitan surgeon and author of "Post mundi fabricam" (around 1180) was considered at that time the surgical text par excellence all over Europe. In the chapter "De bocio" of his magnum opus, he describes several pharmacological and surgical cures, some of which nowadays are reappraised quite scientifically effective.

In modern times, the thyroid was first identified by the anatomist
Anatomy
Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...

 Thomas Wharton (whose name is also eponym
Eponym
An eponym is the name of a person or thing, whether real or fictitious, after which a particular place, tribe, era, discovery, or other item is named or thought to be named...

ised in Wharton's duct of the submandibular gland) in 1656.

Thyroxine was identified only in the 19th century.

In other animals

The thyroid gland is found in all vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s. In fish, it is, in general, 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 tetrapod
Tetrapod
Tetrapods are vertebrate animals having four limbs. Amphibians, reptiles, birds and mammals are all tetrapods; even snakes and other limbless reptiles and amphibians are tetrapods by descent. The earliest tetrapods evolved from the lobe-finned fishes in the Devonian...

s, 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 together. However, there is only ever a single thyroid gland in most mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s, and the shape found in humans is common to many other species.

In larval lamprey
Lamprey
Lampreys are a family of jawless fish, whose adults are characterized by a toothed, funnel-like sucking mouth. Translated from an admixture of Latin and Greek, lamprey means stone lickers...

s, 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 tunicate
Tunicate
Tunicates, also known as urochordates, are members of the subphylum Tunicata, previously known as Urochordata, a group of underwater saclike filter feeders with incurrent and excurrent siphons that is classified within the phylum Chordata. While most tunicates live on the ocean floor, others such...

s and Amphioxus, have a structure very similar to that of larval lampreys, and this also secretes iodine-containing compounds (albeit not thyroxine).

See also

  • Thyroid disease
    Thyroid disease
    -Hyper- and hypofunction:Imbalance in production of thyroid hormones arises from dysfunction of the thyroid gland itself, the pituitary gland, which produces thyroid-stimulating hormone , or the hypothalamus, which regulates the pituitary gland via thyrotropin-releasing hormone . Concentrations of...

  • Thyroid disease in pregnancy
    Thyroid disease in pregnancy
    Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present in pregnancy and the puerperium. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend...

  • Academy of Clinical Thyroidologists
    Academy of Clinical Thyroidologists
    The Academy of Clinical Thyroidologists was founded in May 2005 at the annual meeting of the Association of Clinical Endocrinologists in Washington DC. The Academy is a professional society consisting of 32 members from the U.S. and Italy who specialize in clinical thyroidology...


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