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A two-lobed endocrine gland found in all vertebrates, located in front of and on either side of the trachea in humans, and producing various hormones, such as triiodothyronine and calcitonin.
An endocrine gland found in all vertebrates that produces, stores, and secretes the thyroid hormones. In humans, the gland is located in front of, and on either side of, the trachea. Thyrocalcitonin, one hormone of the thyroid gland, assists in regulating serum calcium by reducing its levels. The iodine-containing hormones thyroxine and triiodothyronine regulate metabolic rate in warm-blooded animals and are essential for normal growth and development. To produce these, the thyroid gland accumulates inorganic iodides from the bloodstream and unites them with the amino acid tyrosine. This activity is regulated by thyrotropic hormone from the anterior lobe of the pituitary gland. See also Thyroid hormone; Thyroxine.
The thyroid gland secretes hormones which are necessary for normal growth and development from fetal life onwards, and for maintenance of normal metabolism in the adult body.
The gland is located just below the larynx and attached to the front of the trachea. The adult gland weighs 10-20 g and consists of two relatively flat oval lobes linked by an isthmus. It is so named because of its resemblance to the classical shield (thureos) used by the ancient Greeks. However, unlike the shield, in any one individual the thyroid is generally asymmetric, with the right lobe being significantly larger than the left. The gland is usually larger in women than in men and it increases slightly in size during pregnancy. This is exploited as an early pregnancy test in some African communities: the neck of a bride is adorned with a tight necklace and pregnancy is indicated when in due course the necklace is broken by the swelling thyroid gland.
The embryonic thyroid originated in the floor of the pharynx and it can be detected as a midline thickening, as early as day 24. By weeks 6-7 the characteristic bilobed structure can be distinguished. At about this time, the gland becomes detached from the pharynx and the developing tissue mass descends into the neck. The two lobes finally come to rest on either side of the trachea with the joining isthmus lying across the front of it. Occasionally the thyroid fails to descend, or may descend too far; the fully developed gland is then found below the root of the tongue or within the thorax. Such developmental abnormalities do not necessarily affect thyroid function.
During its descent down the neck the developing thyroid incorporates ‘C-cells’ into its tissue mass; also two pairs of discrete parathyroid glands become attached to the back surface of the thyroid gland itself. These secrete hormones which regulate the concentration of calcium in the blood: the C-cells secrete the protein calcitonin, and the parathyroids the protein parathyroid hormone. Neither of these are regarded as thyroid hormones since they are not produced by the main mass of thyroid tissue; the latter consists of spherical follicles where the thyroid hormones are synthesized and stored.
The major functional and structural unit of the thyroid is the thyroid follicle. There are many thousands of follicles, and their individual sizes vary considerably, ranging in diameter from 20 to 100 μm (2/100-1/10 mm). A rich network of fenestrated capillary blood vessels surrounds small groups of follicles and there is an impressively high rate of blood flow through the gland as a whole (per unit mass, the flow is twice the flow through the kidneys, which themselves have a much greater blood supply than other organs relative to their size). The even greater flow through an overactive thyroid produces a ‘bruit’ which can be heard when a stethoscope is placed over the gland. The high blood flow ensures an adequate supply of blood-borne nutrients to the follicles — in particular the delivery of iodide derived from the diet — as well as uptake of the thyroid hormones into the bloodstream.
The unique biochemical characteristic of thyroid follicular cells is their ability to concentrate and to utilize dietary iodide. The cell possesses an iodide ‘pump’ which enables it to accumulate iodide internally, so that it can achieve a concentration twenty- to a hundred-fold higher than that in the circulating blood. Two other tissues which share a closely related embryonic origin with the thyroid (some cells of the stomach lining and the salivary glands) also possess this pumping mechanism, but the thyroid is unique in its ability to retain and utilize the iodide for the biosynthesis of its hormones. These hormones are small molecules derived from the amino acid tyrosine and they have iodine incorporated into their structures. There are two thyroid hormones, which have either 3 or 4 atoms of iodine per molecule; they are known respectively as T3 (tri-iodothyronine) and T4 (thyroxine). Both are synthesized within the thyroid follicles and secreted into the bloodstream when the cells are stimulated to extrude them by the thyroid stimulation hormone (TSH) from the pituitary gland. The thyroid hormones in the circulation in turn regulate the production of TSH by the pituitary, switching off TSH production when the appropriate level of T3/T4 is attained in the blood. Thus the ‘pituitary-thyroid axis’ is a classical example of a negative feedback system.
Following the accumulation of iodine in the follicular cells, the T3 and T4 are first synthesized separately and are then incorporated into a much larger molecule known as thyroglobulin. This large glycoprotein, which is sometimes referred to as ‘colloid’ is stored in the hollow interior of each follicle. If a thyroid gland which has been removed is cut across and gently squeezed, the colloid can be observed leaking from the transected follicles as a glistening yellowish fluid. TSH stimulates the release of the T3 and T4 from the thyroglobulin so that the hormones can be secreted from the cells into the bloodstream in a regulated fashion. This hormone storage system is unique in endocrine physiology; it ensures that there is a two-month supply of thyroid hormones in the event that a person encounters an iodine deficient environment. This occurs in many parts of the world, such as some mountainous regions in China and India. However, this capacity to store thyroid hormones within the follicles as thyroglobulin becomes disadvantageous if an individual inadvertently ingests radioactive iodine. This occurred after the huge release into the atmosphere of radioactive isotopes, including radioiodine, during the week following the Chernobyl accident on 26 April 1986. The natural storage of the radioiodine in the follicles delays clearance of the ingested radionuclide and concentrates the damaging radiation on the thyroid. In Belarus and the Ukraine this resulted in a major increase in the incidence of thyroid cancer in the 1990s amongst children born before the accident.
Thyroid hormones circulate in the blood in minute concentrations (nanomolar — of the order of 10-9 × molecular weight per litre). Although this is very low compared with many blood constituents such as glucose or sodium ions, which circulate at millimolar concentrations (a million times greater), it is high relative to hormones in general. The blood concentrations of the thyroid hormones are tightly regulated by TSH and remain very stable in a healthy individual over prolonged periods. Thyroid hormones are relatively insoluble in water and this has two important consequences. Firstly, in the circulation more than 99% of them are linked to specific ‘binding proteins’; this prolongs their half-life in blood, and since the binding is reversible, maintains a biologically active ‘reservoir’ in the circulation. Secondly, on arrival at a target cell, the hormones, being relatively soluble in lipid, are able to cross the plasma membrane of the cell and then bind to specific receptors associated with gene regulation in the nucleus of the cell.
Thyroid hormones regulate the activities of almost all cells in the body. They exert three main classes of action. Firstly they control the basal metabolic rate (BMR). Secondly they influence cell differentiation and growth. Thirdly they may modify the action of other hormones, extending their importance still more widely. Thus a lack of thyroid hormones is manifested in diverse ways. In the developing fetus an inadequate supply leads to impaired brain development with the danger of the infant being borne a cretin. In an adult there is a depressed BMR with attendant lethargy. By contrast, excess thyroid hormones raise the BMR and may lead to cardiac problems due to potentiation by thyroid hormone of the effects of adrenaline.
T3, the form of thyroid hormone which contains only 3 atoms of iodine per molecule, is now considered to be the physiologically active hormone, and T4 to be a precursor of T3, which can be converted to T3 by specific enzymes within the target cells. Since T4 circulates at a concentration about a hundred-fold higher than that of T3, it can therefore be considered to be a storage form of the active hormone. Thus the thyroid system as a whole is designed to buffer any possibility of a reduction in the adequate supply of T3 to target cells: large reserves are maintained in the thyroglobulin stored in the follicles, in the T3 and T4 attached to the circulating binding proteins, and in T4 itself.
— N. J. Marshall
See endocrine. See also goitre; hormones; hyperthyroidism; hypothyroidism.
A highly vascular organ at the front of the neck, consisting of bilateral lobes connected in the middle by a narrow isthmus. The thyroid gland secretes the hormone thyroxine directly into the blood. It is essential to normal body growth in infancy and childhood. It also regulates the metabolic rate in adults.
Thyroid gland. (Thibodeau/Patton, 2002)
For more information on thyroid gland, visit Britannica.com.
A large, bilobed endocrine gland located along the midline of the neck, immediately below the larynx (Adam's apple). The thyroid gland secretes the hormones triiodothyronine and thyroxine, which regulate metabolic rate, and calcitonin, which helps regulate calcium metabolism.
| Thyroid | |
|---|---|
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| Endocrine system | |
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| Thyroid and parathyroid. | |
| Latin | glandula thyroidea |
| Gray's | subject #272 1269 |
| System | endocinal jubachina system |
| Artery | superior thyroid artery, inferior thyroid artery, |
| Vein | superior thyroid vein, middle thyroid vein, inferior thyroid vein, thyreoidea ima |
| Nerve | middle cervical ganglion, inferior cervical ganglion |
| Precursor | 4th Branchial pouch |
| MeSH | Thyroid+Gland |
| Dorlands/Elsevier | g_06/12392768 |
The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck just below the laryngeal prominence. The thyroid controls how quickly the body burns energy, makes proteins, and how sensitive the body should be to other hormones.
The thyroid participates in these processes by producing thyroid hormones, principally thyroxine (T4) and triiodothyronine (T3). These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. Iodine is an essential component of both T3 and T4. The thyroid also produces the hormone calcitonin, which plays a role in calcium homeostasis.
The thyroid is controlled by the hypothalamus and pituitary. The gland gets its name from the Greek word for "shield", after its shape, a double-lobed structure. Hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid) are the most common problems of the thyroid gland. Specialists are called Thyroidologists.
The thyroid is situated on the anterior side of the neck, starting at the oblique line on the thyroid cartilage (just below the laryngeal prominence or Adam's apple), and extending to the 6th Tracheal ring (C-shaped cartilagenous ring of the trachea). It is inappropriate to demarcate the gland's upper and lower border with vertebral levels as it moves position in relation to these during swallowing. It lies over the trachea and is covered by layers of pretracheal fascia (allowing it to move), muscle and skin.
The thyroid is one of the larger endocrine glands - 10-20 grams in adults - and butterfly-shaped. The wings correspond to the lobes and the body to the isthmus of the thyroid. The isthmus overlies tracheal rings 2, 3 and 4. The thyroid may enlarge substantially during pregnancy and when affected by a variety of diseases.
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 and the copula linguae at a point latter indicated by the foramen cecum. Subsequently the thyroid descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct. Over the next few weeks, it migrates to the base of the neck. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct.
Follicles of the thyroid begin to make colloid in the 11th week and thyroxine by the 18th week.
At a histological level, there are three primary features of the thyroid:
| Feature | Description |
| Follicles | The thyroid is composed of spherical follicles that selectively absorb iodine (as iodide ions, I-) from the blood for production of thyroid hormones. Twenty-five percent of all the body's iodide ions are in the thyroid gland. Inside the follicles, colloids rich in a protein called thyroglobulin serve as a reservoir of materials for thyroid hormone production and, to a lesser extent, act as a reservoir for the hormones themselves. |
| Thyroid epithelial cells (or "follicular cells") |
The follicles are surrounded by a single layer of thyroid epithelial cells, which secrete T3 and T4. |
| Parafollicular cells (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. |
The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver, kidney and spleen. T3 is about ten times more active than T4.[1]
Thyroxine is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (TG). Iodine is captured with the "iodine trap" by the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO)[2] 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 (TSH), the follicular cells reabsorb TG and proteolytically cleave the iodinated tyrosines from TG, forming T4 and T3 (in T3, one iodine is absent compared to T4), and releasing them into the blood. Deiodinase enzymes convert T4 to T3.[3] Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3.[1]
Cells of the brain are a major target for the thyroid hormones T3 and T4. Thyroid hormones play a particularly crucial role in brain development during pregnancy.[4] A transport protein (OATP1C1) has been identified that seems to be important for T4 transport across the blood brain barrier.[5] A second transport protein (MCT8) is important for T3 transport across brain cell membranes.[5]
In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. 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 hormones and retinoic acid, thyroid hormones cross the cell membrane and bind to intracellular receptors (α1, α2, β1 and β2), which act alone, in pairs or together with the retinoid X-receptor as transcription factors to modulate DNA transcription[1].
The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH), released by the anterior pituitary. The thyroid and thyrotropes form a negative feedback loop: TSH production is suppressed when the T4 levels are high, and vice versa. The TSH production itself is modulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus and secreted at an increased rate in situations such as cold (in which an accelerated metabolism would generate more heat). TSH production is blunted by somatostatin (SRIH), rising levels of glucocorticoids and sex hormones (estrogen and testosterone), and excessively high blood iodide concentration.
An additional hormone produced by the thyroid contributes to the regulation of blood calcium levels. Parafollicular cells produce calcitonin in response to hypercalcemia. Calcitonin stimulates movement of calcium into bone, in opposition to the effects of parathyroid hormone (PTH). However, calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid, but not the parathyroids.
It may be used diagnostically as a tumor marker for a form of thyroid cancer (medullary thyroid adenocarcinoma), in which high calcitonin levels may be present and elevated levels after surgery may indicate recurrence. It may even be used on biopsy samples from suspicious lesions (e.g. swollen lymph nodes) to establish whether they are metastasis of the original cancer.
Calcitonin can be used therapeutically for the treatment of hypercalcemia or osteoporosis.
In areas of the world where iodine (essential for the production of thyroxine, which contains four iodine atoms) is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre.
Thyroxine is critical to the regulation of metabolism and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; conversely, administering thyroxine will trigger metamorphosis.
In humans, children born with thyroid hormone deficiency will have physical growth and development problems, and brain development can also be severely impaired, in the condition referred to as cretinism. Newborn children in many developed countries are now routinely tested for thyroid hormone deficiency as part of newborn screening by analysis of a drop of blood. Children with thyroid hormone deficiency are treated by supplementation with synthetic thyroxine, which enables them to grow and develop normally.
Because of the thyroid's selective uptake and concentration of what is a fairly rare element, it is sensitive to the effects
of various radioactive
The use of iodised salt 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 mandatory. Potassium iodide and Sodium iodide are the most active forms of supplemental iodine.
Medication linked to thyroid disease includes amiodarone, lithium salts, some types of interferon and IL-2.
Nodules of the thyroid may or may not be cancer. Medical ultrasonography can help determine their nature because some of the characteristics of benign and malignant nodules differ. The main characteristics of a thyroid nodule on high frequency thyroid ultrasound are as follows:
| Possible cancer | Benign characteristics |
| irregular border | smooth borders |
| hypoechoic (less echogenic than the surrounding tissue) | hyperechoic |
| microcalcifications | - |
| taller than wide shape on transverse study | - |
| significant intranodular blood flow by power Doppler | - |
| - | "comet tail" artifact as sound waves bounce off intranodular colloid |
Ultrasonography is not always able to separate benign from malignant nodules with complete certainty. In suspicious cases, a tissue sample is often obtained by biopsy for microscopic examination.
Thyroid scintigraphy, imaging of the thyroid with the aid of radioactive iodine, usually iodine-123 (123I), is performed in the nuclear medicine department of a hospital or clinic. Radioiodine collects in the thyroid gland before being excreted in the urine. While in the thyroid the radioactive emissions can be detected by a camera, producing a rough image of the shape (a radiodine scan) and tissue activity (a radioiodine uptake) of the thyroid gland.
A normal radioiodine scan shows even uptake and activity throughout the gland. Irregularity can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive, different from the rest. For example, a nodule that is overactive ("hot") to the point of suppressing the activity of the rest of the gland is usually a thyrotoxic adenoma, a surgically curable form of hyperthyroidism that is hardly ever malignant. In contrast, finding that a substantial section of the thyroid is inactive ("cold") may indicate an area of non-functioning tissue such as thyroid cancer.
The amount of radioactivity can be counted as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8 to 35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland as may occur with hypothyroidism or hyperthyroidism is usually reflected in decreased or increased radioiondine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism.
A medical biopsy refers to the obtaining of a tissue sample for examination under the microscope or other testing, usually to distinguish cancer from noncancerous conditions. Thyroid tissue may be obtained for biopsy by fine needle aspiration or by surgery.
Needle aspiration has the advantage of being a brief, safe, outpatient procedure that is safer and less expensive than surgery and does not leave a visible scar. Needle biopsies became widely used in the 1980s, but it was recognized that accuracy of identification of cancer was good but not perfect. The accuracy of the diagnosis depends on obtaining tissue from all of the suspicious areas of an abnormal thyroid gland. The reliability of needle aspiration is increased when sampling can be guided by ultrasound, and over the last 15 years, this has become the preferred method for thyroid biopsy in North America.
Levothyroxine is a stereoisomer of thyroxine which is degraded much slower and can be administered once daily in patients with hypothyroidism.
Graves' disease may be treated with the thioamide drugs propylthiouracil, carbimazole or methimazole, or rarely with Lugol's solution. Hyperthyroidism as well as thyroid tumors may be treated with radioactive iodine.
Percutaneous Ethanol Injections, PEI, for therapy of recurrent thyroid cysts, and metastatic thyroid cancer lymph nodes, as an alternative to the usual surgical method.
Thyroid surgery is performed for a variety of reasons. A nodule or lobe of the thyroid is sometimes removed for biopsy or for the presence of an autonomously functioning adenoma causing hyperthyroidism. A large majority of the thyroid may be removed, a subtotal thyroidectomy, to treat the hyperthyroidism of Graves' disease, or to remove a goitre that is unsightly or impinges on vital structures. A complete thyroidectomy of the entire thyroid, including associated lymph nodes, is the preferred treatment for thyroid cancer. Removal of the bulk of the thyroid gland usually produces hypothyroidism, unless the person takes thyroid hormone replacement.
If the thyroid gland must be removed surgically, care must be taken to avoid damage to adjacent structures, the parathyroid glands and the recurrent laryngeal nerve. Both are susceptible to accidental removal and/or injury during thyroid surgery. The parathyroid glands produce parathyroid hormone (PTH), a hormone needed to maintain adequate amounts of calcium in the blood. Removal results in hypoparathyroidism and a need for supplemental calcium and vitamin D each day. The recurrent laryngeal nerves provide motor control for all external muscles of the larynx except for the cricothyroid muscle, also runs along the posterior thyroid. Accidental laceration of either of the two or both recurrent laryngeal nerves may cause paralysis of the vocal cords and their associated muscles, changing the voice quality.
Large goiters that cause symptoms, but do not harbor cancer, after evaluation, and biopsy of suspicious nodules can be treated by an alternative therapy with radioiodine. The iodine uptake can be high in countries with iodine deficiency, but low in iodine sufficient countries. The 1999 release of rhTSH thyrogen in the USA, can boost the uptakes to 50-60% allowing the therapy with iodine 131. The gland shrinks by 50-60%, but can cause hypothyroidism, and rarely pain syndrome cause by radiation thyroiditis that is short lived and treated by steroids.
There are several findings that evidence a great interest for thyroid disorders just in the Medieval Medical School of Salerno (XII Century). Rogerius Salernitanus, 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 magnus opum he describes several pharmacological and surgical cures, some of which nowadays are reappraised quite scientifically effective.[6]
In modern times, the thyroid was first identified by the anatomist Thomas Wharton (whose name is also eponymised in Wharton's duct of the submandibular gland) in 1656.[7]
Thyroid hormone (or thyroxin) was only identified in the 19th century.
 |
 Section of the neck at about the level of the sixth cervical vertebra. |
 Muscles of the neck. Anterior view. |
 The arch of the aorta, and its branches. |
 Superficial dissection of the right side of the neck, showing the carotid and subclavian arteries. |
 Diagram showing common arrangement of thyroid veins. |
 Sagittal section of nose mouth, pharynx, and larynx. |
 Muscles of the pharynx, viewed from behind, together with the associated vessels and nerves. |
 The position and relation of the esophagus in the cervical region and in the posterior mediastinum. Seen from behind. |
 Section of thyroid gland of sheep. X 160. |
 The thymus of a full-term fetus, exposed in situ. |
 Thyoid histology |
| Human anatomy, endocrine system: endocrine glands | |
|---|---|
| Hypothalamic/pituitary axes | Adrenal axis (Adrenal gland) • Thyroid axis (Thyroid gland, Parathyroid gland) • Gonadal axis (Testes, Ovaries, Corpus luteum) |
| Other | Pineal gland • Islets of pancreas |
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