View source for Thyroid

{{Short description|Endocrine gland in the neck}}
{{confuse|Thymus}}
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{{Infobox anatomy
| Name = Thyroid
| pronunciation = {{IPAc-en|ˈ|θ|aɪ|r|ɔɪ|d}}
| Latin = glandula thyreoidea
| Greek = θυρεοειδής
| Image = Anterior thyroid.jpg
| Caption = The human thyroid (tan), as viewed from the front; and arteries (red) supplying the gland. 
| Image2 = Thyroid dummy.jpg
| Caption2 = The thyroid gland is a butterfly-shaped gland located in the neck below the [[Adam's apple]]. 
| Width = 
| Precursor = [[Thyroid diverticulum]] (an extension of [[endoderm]] into 2nd [[pharyngeal arch]])
| System = [[Endocrine system]]
| Artery = [[Superior thyroid artery|Superior]], [[Inferior thyroid artery|inferior thyroid arteries]]
| Vein = [[Superior thyroid vein|Superior]], [[Middle thyroid vein|middle]], [[inferior thyroid vein]]s
| Nerve = 
| Lymph = 
}}

The '''thyroid''', or '''thyroid gland''', is an [[endocrine gland]] in [[vertebrates]]. In humans, it is a butterfly-shaped gland located in the neck below the [[Adam's apple]]. It consists of two connected [[lobe (anatomy)|lobes]]. The lower two thirds of the lobes are connected by a thin band of [[Connective tissue|tissue]] called the '''isthmus''' ({{plural form}}: '''isthmi''').  Microscopically, the functional unit of the thyroid gland is the spherical [[Thyroid follicular cell#Location|thyroid follicle]], lined with [[thyroid follicular cell|follicular cells]] (thyrocytes), and occasional [[parafollicular cell]]s that surround a [[follicular lumen|lumen]] containing [[colloid]]. 

The thyroid gland secretes three hormones: the two [[thyroid hormones]]{{Snd}}[[triiodothyronine|triiodothyronine (T<sub>3</sub>)]] and [[thyroid hormone|thyroxine (T<sub>4</sub>)]]{{Snd}}and a [[peptide hormone]], [[calcitonin]]. The thyroid hormones influence the [[basal metabolic rate|metabolic rate]] and [[protein biosynthesis|protein synthesis]] and growth and development in children. Calcitonin plays a role in [[Calcium metabolism#Regulation of calcium metabolism|calcium homeostasis]].{{sfn|Guyton & Hall|2011|p=907}} 

Secretion of the two thyroid hormones is regulated by [[thyroid-stimulating hormone]] (TSH), which is secreted from the [[anterior pituitary]] gland. TSH is regulated by [[thyrotropin-releasing hormone]] (TRH), which is produced by the [[hypothalamus]].<ref name="boron">{{cite book| vauthors = Boron WF, Boulpaep EL |title=Medical Physiology|date=2012|publisher=Saunders|location=Philadelphia|page=1052|isbn=978-1-4377-1753-2|edition=2nd}}</ref>

Thyroid disorders include [[hyperthyroidism]], [[hypothyroidism]], thyroid [[inflammation]] ([[thyroiditis]]), thyroid enlargement ([[goitre]]), [[thyroid nodule]]s, and [[thyroid cancer]]. Hyperthyroidism is characterized by excessive secretion of thyroid hormones: the most common cause is the [[autoimmune disorder]] [[Graves' disease]]. Hypothyroidism is characterized by a deficient secretion of thyroid hormones: the most common cause is [[iodine deficiency]]. In iodine-deficient regions, hypothyroidism (due to iodine deficiency) is the leading cause of preventable [[intellectual disability]] in children.{{sfn|Harrison's|2011|pp=2913,2918}} In iodine-sufficient regions, the most common cause of hypothyroidism is the autoimmune disorder [[Hashimoto's thyroiditis]]. 
{{TOC limit|4}}

== Structure ==
===Features===
[[File:Illu08 thyroid.jpg|thumb| The thyroid gland surrounds the [[cricoid cartilage|cricoid]] and [[trachea|tracheal cartilages]] and consists of two lobes. This image shows a variant thyroid with a pyramidal lobe emerging from the middle of the thyroid.|alt=Image showing the thyroid gland surrounding the cricoid cartilage]]

The thyroid gland is a butterfly-shaped organ composed of two lobes, left and right, connected by a narrow tissue band, called an "isthmus".{{sfn|Gray's Anatomy|2008|pp=462–4}} It weighs 25 grams in adults, with each lobe being about 5&nbsp;cm long, 3&nbsp;cm wide, and 2&nbsp;cm thick and the isthmus about 1.25&nbsp;cm in height and width.{{sfn|Gray's Anatomy|2008|pp=462–4}} The gland is usually larger in women than in men, and increases in size during pregnancy.{{sfn|Gray's Anatomy|2008|pp=462–4}}{{sfn|Elsevier's|2007|p=342}}

The thyroid is near the front of the neck, lying against and around the front of the [[larynx]] and [[trachea]].{{sfn|Gray's Anatomy|2008|pp=462–4}} The [[thyroid cartilage]] and [[cricoid cartilage]] lie just above the gland, below the [[Adam's apple]]. The isthmus extends from the second to third [[rings of the trachea]], with the uppermost part of the lobes extending to the thyroid cartilage and the lowermost around the fourth to sixth tracheal rings.{{sfn|Elsevier's|2007|pp=342–3}} The [[infrahyoid muscles]] lie in front of the gland and the [[sternocleidomastoid muscle]] to the side.<ref name="isbn0-443-07168-3">{{cite book | last1 = Ellis | first1 = Harold | first2 = Susan | last2 = Standring | last3 = Gray | first3 = Henry David | name-list-style = vanc |title=Gray's anatomy: the anatomical basis of clinical practice |publisher=Elsevier Churchill Livingstone |location=St. Louis, Mo |year=2005 |pages=[https://archive.org/details/graysanatomyanat0000unse/page/538 538–539] |isbn=978-0-443-07168-3 |url=https://archive.org/details/graysanatomyanat0000unse/page/538 }}</ref> Behind the outer wings of the thyroid lie the two [[carotid artery|carotid arteries]]. The trachea, larynx, lower pharynx and esophagus all lie behind the thyroid.{{sfn|Elsevier's|2007|p=342}} In this region, the [[recurrent laryngeal nerve]]<ref name="Netter">{{cite book|last1=Netter|first1=Frank H. | name-list-style = vanc |title=Atlas of Human Anatomy Including Student Consult Interactive Ancillaries and Guides.|date=2014|publisher=W B Saunders Co|location=Philadelphia, Penn.|isbn=978-1-4557-0418-7|page=27|edition=6th}}</ref> and the inferior thyroid artery pass next to or in the ligament.<ref name=PAGE2009>{{cite journal | vauthors = Page C, Cuvelier P, Biet A, Boute P, Laude M, Strunski V | title = Thyroid tubercle of Zuckerkandl: anatomical and surgical experience from 79 thyroidectomies | journal = The Journal of Laryngology and Otology | volume = 123 | issue = 7 | pages = 768–71 | date = July 2009 | pmid = 19000342 | doi = 10.1017/s0022215108004003 | s2cid = 22063700 }}</ref> Typically, four [[parathyroid gland]]s, two on each side, lie on each side between the two layers of the thyroid capsule, at the back of the thyroid lobes.{{sfn|Gray's Anatomy|2008|pp=462–4}}

The thyroid gland is covered by a thin fibrous capsule,{{sfn|Gray's Anatomy|2008|pp=462–4}} which has an inner and an outer layer. The inner layer extrudes into the gland and forms the [[septum|septa]] that divide the thyroid tissue into microscopic lobules.{{sfn|Gray's Anatomy|2008|pp=462–4}} The outer layer is continuous with the [[pretracheal fascia]], attaching the gland to the cricoid and thyroid cartilages{{sfn|Elsevier's|2007|p=342}} via a thickening of the fascia to form the posterior [[suspensory ligament of thyroid gland]], also known as Berry's ligament.{{sfn|Elsevier's|2007|p=342}} This causes the thyroid to move up and down with the movement of these cartilages when swallowing occurs.{{sfn|Elsevier's|2007|p=342}}

===Blood, lymph and nerve supply===
The thyroid is supplied with arterial blood from the [[superior thyroid artery]], a branch of the [[external carotid artery]], and the [[inferior thyroid artery]], a branch of the [[thyrocervical trunk]], and sometimes by an [[Human variability|anatomical variant]] the [[thyroid ima artery]],{{sfn|Gray's Anatomy|2008|pp=462–4}} which has a variable origin.{{sfn|Elsevier's|2007|p=343}} The superior thyroid artery splits into anterior and posterior branches supplying the thyroid, and the inferior thyroid artery splits into superior and inferior branches.{{sfn|Gray's Anatomy|2008|pp=462–4}} The superior and inferior thyroid arteries join behind the outer part of the thyroid lobes.{{sfn|Elsevier's|2007|p=343}} The venous blood is drained via [[superior thyroid vein|superior]] and [[middle thyroid vein]]s, which drain to the [[internal jugular vein]], and via the [[inferior thyroid veins]]. The inferior thyroid veins originate in a network of veins and drain into the left and right [[brachiocephalic vein]]s.{{sfn|Gray's Anatomy|2008|pp=462–4}} Both arteries and veins form a plexus between the two layers of the capsule of the thyroid gland.{{sfn|Elsevier's|2007|p=343}}

[[Lymph]]atic drainage frequently passes the [[prelaryngeal lymph nodes]] (located just above the isthmus) and the [[pretracheal lymph nodes|pretracheal]] and [[paratracheal lymph nodes]].{{sfn|Gray's Anatomy|2008|pp=462–4}} The gland receives [[sympathetic nervous system|sympathetic nerve]] supply from the superior, middle and inferior cervical ganglion of the [[sympathetic trunk]].{{sfn|Gray's Anatomy|2008|pp=462–4}} The gland receives [[parasympathetic nerve]] supply from the [[superior laryngeal nerve]] and the [[recurrent laryngeal nerve]].{{sfn|Gray's Anatomy|2008|pp=462–4}}

===Variation===
[[File:Sobo 1906 444.png|thumb|right|upright=0.85|Clear ''pyramidal lobe'' (center) as viewed from the front]]
There are many [[anatomical variation|variants]] in the size and shape of the thyroid gland, and in the position of the embedded parathyroid glands.{{sfn|Elsevier's|2007|p=342}}

Sometimes there is a third lobe present called the ''pyramidal lobe''.{{sfn|Elsevier's|2007|p=342}} When present, this lobe often stretches up to the hyoid bone from the thyroid isthmus and may be one to several divided lobes.{{sfn|Gray's Anatomy|2008|pp=462–4}} The presence of this lobe ranges in reported studies from 18.3%<ref name="MedJ">{{cite journal |vauthors=Cicekcibasi AE, Salbacak A, Seker M, Ziylan T, Tuncer I, Buyukmumcu M |date=April 2007 |title=Developmental variations and clinical importance of the fetal thyroid gland. A morphometric study |journal=Saudi Medical Journal |volume=28 |issue=4 |pages=524–8 |pmid=17457471 }}</ref> to 44.6%.<ref>{{cite journal | vauthors = Kim DW, Jung SL, Baek JH, Kim J, Ryu JH, Na DG, Park SW, Kim JH, Sung JY, Lee Y, Rho MH | display-authors = 6 | title = The prevalence and features of thyroid pyramidal lobe, accessory thyroid, and ectopic thyroid as assessed by computed tomography: a multicenter study | journal = Thyroid | volume = 23 | issue = 1 | pages = 84–91 | date = January 2013 | pmid = 23031220 | doi = 10.1089/thy.2012.0253 | url = https://ir.ymlib.yonsei.ac.kr/handle/22282913/86792 }}</ref> It was shown to more often arise from the left side and occasionally separated.<ref name=MedJ/> The pyramidal lobe is also known as [[Pierre Lalouette|Lalouette's]] pyramid.<ref>{{cite book| first = William Alexander Newman | last = Dorland | veditors = Anderson DM | title = Dorland'sIllustrated Medical Dictionary | edition = 32nd |date=2012 |publisher=Elsevier Saunders |isbn=978-1-4160-6257-8 |pages=999 redirect to 1562}}</ref> The pyramidal lobe is a remnant of the [[thyroglossal duct]], which usually wastes away during the thyroid gland's descent.{{sfn|Elsevier's|2007|p=342}} Small accessory thyroid glands may in fact occur anywhere along the thyroglossal duct, from the [[foramen cecum (tongue)|foramen cecum]] of the tongue to the position of the thyroid in the adult.{{sfn|Gray's Anatomy|2008|pp=462–4}} A small horn at the back of the thyroid lobes, usually close to the recurrent laryngeal nerve and the inferior thyroid artery, is called [[Zuckerkandl's tubercle (thyroid gland)|Zuckerkandl's tubercle]].<ref name=PAGE2009 />

Other variants include a [[levator muscle of thyroid gland]], connecting the isthmus to the body of the [[hyoid bone]],{{sfn|Elsevier's|2007|p=342}} and the presence of the small [[thyroid ima artery]].{{sfn|Elsevier's|2007|p=342}}

===Microanatomy===
[[File:Thyroid-histology.jpg|thumb|Section of a thyroid gland under the microscope. 1 colloid, 2 follicular cells, 3 [[Endothelium|endothelial]] cells]] 
At the [[histology|microscopic level]], there are three primary features of the thyroid—[[thyroid follicle]]s, [[thyroid follicular cell]]s, and [[parafollicular cell]]s, first discovered by Geoffery Websterson in 1664.<ref>{{Cite book|last1 = Fawcett|first1 = Don| last2 = Jensh | first2 = Ronald | name-list-style = vanc |title = Bloom & Fawcett's Concise Histology|publisher = Arnold Publishers|year = 2002|location = New York|pages = 257–258|isbn = 978-0-340-80677-7}}</ref>

;Follicles
[[Thyroid follicular cell#Location|Thyroid follicles]] are small spherical groupings of cells 0.02–0.9mm in diameter that play the main role in thyroid function.{{sfn|Gray's Anatomy|2008|pp=462–4}} They consist of a rim that has a rich blood supply, nerve and lymphatic presence, that surrounds a core of [[colloid]] that consists mostly of thyroid hormone precursor proteins called [[thyroglobulin]], an [[iodine|iodinated]] [[glycoprotein]].{{sfn|Gray's Anatomy|2008|pp=462–4}}<ref name="Wheaters2006">{{cite book| first1 = Paul R | last1 = Wheater | first2 = Barbara | last2 = Young | name-list-style = vanc |title=Wheater's functional histology: a text and colour atlas|url=https://archive.org/details/wheatersfunction00youn|url-access=limited|date=2006|publisher=Churchill Livingstone|location=Oxford|isbn=978-0-443-06850-8|pages=[https://archive.org/details/wheatersfunction00youn/page/n741 333]–335|edition=5th}}</ref>

;Follicular cells
The core of a follicle is surrounded by a single layer of follicular cells. When stimulated by thyroid stimulating hormone (TSH), these secrete the thyroid hormones T<sub>3</sub> and T<sub>4</sub>. They do this by transporting and metabolising the thyroglobulin contained in the colloid.{{sfn|Gray's Anatomy|2008|pp=462–4}} Follicular cells vary in shape from flat to cuboid to columnar, depending on how active they are.{{sfn|Gray's Anatomy|2008|pp=462–4}}<ref name=Wheaters2006 />

;Follicular lumen
The ''follicular lumen'' is the fluid-filled space within a follicle of the thyroid gland. There are hundreds of follicles within the thyroid gland. A follicle is formed by a spherical arrangement of [[thyroid follicular cell|follicular cells]]. The follicular lumen is filled with ''colloid'', a concentrated solution of [[thyroglobulin]] and is the site of synthesis of the thyroid hormones [[thyroxine]] (T4) and [[triiodothyronine]] (T3).<ref>[http://www.expertconsultbook.com/expertconsult/ob/book.do?method=display&type=bookPage&decorator=none&eid=4-u1.0-B978-1-4160-5583-9..00072-1--s0040&isbn=9781416055839 The Thyroid Follicle] {{Webarchive|url=https://archive.today/20130123031837/http://www.expertconsultbook.com/expertconsult/ob/book.do?method=display&type=bookPage&decorator=none&eid=4-u1.0-B978-1-4160-5583-9..00072-1--s0040&isbn=9781416055839 |date=2013-01-23 }}, ''Endocrinology'' by J. Larry Jameson, MD, PhD and Leslie J. De Groot, MD, chapter 72</ref>

;Parafollicular cells
Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells.{{sfn|Gray's Anatomy|2008|pp=462–4}} These cells secrete [[calcitonin]] and so are also called C cells.<ref>{{cite journal | vauthors = Hazard JB | title = The C cells (parafollicular cells) of the thyroid gland and medullary thyroid carcinoma. A review | journal = The American Journal of Pathology | volume = 88 | issue = 1 | pages = 213–50 | date = July 1977 | pmid = 18012 | pmc = 2032150 }}</ref>

==Development==
[[Image:Gray42.png|thumb|Floor of pharynx of embryo between 35 and 37 days after fertilization.]]
In the [[human embryogenesis|development of the embryo]], at 3–4 weeks [[Gestational age (obstetrics)|gestational age]], the thyroid gland appears as an [[epithelium|epithelial]] proliferation in the floor of the pharynx at the base of the tongue between the [[Median tongue bud|''tuberculum impar'']] and the ''[[copula linguae]]''. The copula soon becomes covered over by the [[hypopharyngeal eminence]]<ref name="Larsen">{{cite book |last1=Larsen |first1=William J. |name-list-style = vanc |title=Human embryology |url=https://archive.org/details/humanembryology0003lars |url-access=registration |date=2001 |publisher=Churchill Livingstone |location=Philadelphia, Pa. |isbn=978-0-443-06583-5 |pages=[https://archive.org/details/humanembryology0003lars/page/372 372]–374 |edition=3.}}</ref> at a point later indicated by the [[Tongue|foramen cecum]]. The thyroid then descends in front of the pharyngeal gut as a bilobed [[thyroid diverticulum|diverticulum]] through the [[thyroglossal duct]]. Over the next few weeks, it migrates to the base of the neck, passing in front of the hyoid bone. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct. At the end of the fifth week the thyroglossal duct degenerates, and over the following two weeks the detached thyroid migrates to its final position.<ref name=Larsen/>

The [[prenatal development|fetal]] [[hypothalamus]] and [[pituitary]] start to secrete [[thyrotropin-releasing hormone]] (TRH) and [[thyroid-stimulating hormone]] (TSH). TSH is first measurable at 11 weeks.{{sfn|Greenspan's|2011|p=179}} By 18–20 weeks, the production of [[thyroxine]] (T<sub>4</sub>) reaches a clinically significant and self-sufficient level.{{sfn|Greenspan's|2011|p=179}}<ref name=Eugster>{{Cite book |last1 = Eugster |first1 = Erica A. |last2 = Pescovitz |first2 = Ora Hirsch |name-list-style = vanc |title=Pediatric endocrinology: mechanisms, manifestations and management |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2004 |page=493 (Table 33–3) |isbn=978-0-7817-4059-3 }}</ref> Fetal [[triiodothyronine]] (T<sub>3</sub>) remains low, less than 15&nbsp;ng/dL until 30 weeks, and increases to 50&nbsp;ng/dL at [[pregnancy#Childbirth maturity stages|full-term]].<ref name=Eugster/> The [[fetus]] needs to be self-sufficient in thyroid hormones in order to guard against [[neurodevelopmental disorder]]s that would arise from [[maternal hypothyroidism]].<ref>{{cite journal |vauthors = Zoeller RT |title = Transplacental thyroxine and fetal brain development |journal = The Journal of Clinical Investigation |volume = 111 |issue = 7 |pages = 954–7 |date = April 2003 |pmid = 12671044 |pmc = 152596 |doi = 10.1172/JCI18236 }}</ref> The presence of sufficient iodine is essential for healthy neurodevelopment.<ref name=":1">{{cite web |url=https://www.who.int/elena/titles/iodine_pregnancy/en/ |archive-url=https://web.archive.org/web/20140104171410/http://www.who.int/elena/titles/iodine_pregnancy/en/ |archive-date=January 4, 2014 |title=Iodine supplementation in pregnant and lactating women |website=World Health Organization |language=en-GB |access-date=2016-11-13}}</ref>

The [[neuroendocrine cell|neuroendocrine]] [[parafollicular cell]]s, also known as C cells, responsible for the production of [[calcitonin]], are derived from foregut endoderm. This part of the thyroid then first forms as the [[ultimopharyngeal body]], which begins in the ventral fourth [[Pharyngeal pouch (embryology)|pharyngeal pouch]] and joins the primordial thyroid gland during its descent to its final location.<ref name=LANGMAN>{{cite book |first1 = Jan |last1 = Langman |first2 = T W |last2 = Sadler |first3 = Susan L |last3 = Sadler-Redmond |first4 = Kathryn |last4 = Tosney |first5 = Jennifer |last5 = Byrne |first6 = Hytham |last6 = Imseis |name-list-style = vanc |title=Langman's Medical Embryology |isbn=978-1-4511-9164-6 |pages=285–6,293 |edition=13th |year=2015 |publisher = Wolters Kluwer }}</ref>

Aberrations in [[prenatal development]] can result in various forms of [[thyroid dysgenesis]] which can cause [[congenital hypothyroidism]], and if untreated this can lead to [[cretinism]].{{sfn|Greenspan's|2011|p=179}}

== Function ==
[[File:Thyroid system.svg|thumb|upright=1.25|The [[thyroid hormone]]s [[triiodothyronine|T<sub>3</sub>]] and [[thyroxine|T<sub>4</sub>]] have a number of metabolic, cardiovascular and developmental effects on the body. The production is stimulated by release of thyroid stimulating hormone (TSH), which in turn depends on release of thyrotropin releasing hormone (TRH). Every downstream hormone has [[negative feedback]] and decreases the level of the hormone that stimulates its release.|alt=Diagram explaining the relationship between the thyroid hormones T<sub>3</sub> and T<sub>4</sub>, thyroid stimulating hormone (TSH), and thyrotropin releasing hormone (TRH)]]

===Thyroid hormones===
{{Main|Thyroid hormones}}

The primary function of the thyroid is the production of the iodine-containing [[thyroid hormones]], [[triiodothyronine]] (T<sub>3</sub>) and [[thyroxine]] or tetraiodothyronine (T<sub>4</sub>) and the [[peptide hormone]] [[calcitonin]].{{sfn|Davidson's|2010|p=736}} The thyroid hormones are created from [[iodine]] and [[tyrosine]]. T<sub>3</sub> is so named because it contains three atoms of iodine per molecule and T<sub>4</sub> contains four atoms of iodine per molecule.{{sfn|Guyton & Hall|2011|p=909}} The thyroid hormones have a wide range of effects on the human body. These include:

* '''Metabolic.''' The thyroid hormones increase the [[basal metabolic rate]] and have effects on almost all body tissues.{{sfn|Guyton & Hall|2011|p=934}} Appetite, the absorption of substances, and gut motility are all influenced by thyroid hormones.{{sfn|Guyton & Hall|2011|p=937}} They increase the absorption in the gut, [[gluconeogenesis|generation]], [[glucose uptake|uptake by cells]], and [[glycolysis|breakdown]] of glucose.{{sfn|Guyton & Hall|2011|p=936}} They stimulate the [[lipolysis|breakdown of fats]], and increase the number of [[free fatty acid]]s.{{sfn|Guyton & Hall|2011|p=936}} Despite increasing free fatty acids, thyroid hormones decrease [[cholesterol]] levels, perhaps by increasing the rate of secretion of cholesterol in [[bile]].{{sfn|Guyton & Hall|2011|p=936}} 
* '''Cardiovascular.''' The hormones increase the rate and strength of the heartbeat. They increase the rate of breathing, intake and consumption of oxygen, and increase the activity of [[mitochondria]].{{sfn|Guyton & Hall|2011|p=937}} Combined, these factors increase blood flow and the body's temperature.{{sfn|Guyton & Hall|2011|p=937}} 
* '''Developmental.''' Thyroid hormones are important for normal development.{{sfn|Guyton & Hall|2011|p=936}} They increase the growth rate of young people,{{sfn|Guyton & Hall|2011|p=935-6}} and cells of the developing brain are a major target for the thyroid hormones T<sub>3</sub> and T<sub>4</sub>. Thyroid hormones play a particularly crucial role in brain maturation during fetal development and first few years of postnatal life{{sfn|Guyton & Hall|2011|p=936}}
* '''Other.''' The thyroid hormones also play a role in maintaining normal sexual function, sleep, and thought patterns. Increased levels are associated with increased speed of thought generation but decreased focus.{{sfn|Guyton & Hall|2011|p=937}} Sexual function, including libido and the maintenance of a normal [[menstrual cycle]], are influenced by thyroid hormones.{{sfn|Guyton & Hall|2011|p=937}}

After secretion, only a very small proportion of the thyroid hormones travel freely in the blood. Most are bound to [[thyroxine-binding globulin]] (about 70%), [[transthyretin]] (10%), and [[serum albumin|albumin]] (15%).{{sfn|Greenspan's|2011|p=169}} Only the 0.03% of T<sub>4</sub> and 0.3% of T<sub>3</sub> traveling freely have hormonal activity.<ref name=bowen>{{cite web| vauthors = Bowen R |title=Thyroid Hormone Receptors|url=http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/receptors.html|website=Colorado State University|access-date=22 February 2015|date=2000|archive-url=https://web.archive.org/web/20110927050157/http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/receptors.html|archive-date=27 September 2011}}</ref> In addition, up to 85% of the T<sub>3</sub> in blood is produced following conversion from T<sub>4</sub> by [[iodothyronine deiodinase]]s in organs around the body.{{sfn|Davidson's|2010|p=736}}

Thyroid hormones act by crossing the [[cell membrane]] and binding to [[intracellular receptor|intracellular]] [[nuclear receptor|nuclear]] [[thyroid hormone receptor]]s [[thyroid hormone receptor#Isoforms|TR-α<sub>1</sub>, TR-α<sub>2</sub>, TR-β<sub>1</sub>, and TR-β<sub>2</sub>]], which bind with [[hormone response element]]s and [[transcription factor]]s to modulate [[DNA transcription]].<ref name=bowen />{{sfn|Greenspan's|2011|p=178}} In addition to these actions on DNA, the thyroid hormones also act within the cell membrane or within cytoplasm via reactions with [[enzyme]]s, including [[Plasma membrane Ca2+ ATPase|calcium ATPase]], [[adenylyl cyclase]], and [[glucose transporter]]s.{{sfn|Greenspan's|2011|p=179}}

===Hormone production===
[[File:Thyroid hormone synthesis.png|thumb|upright=2|Synthesis of the [[thyroid hormone]]s, as seen on an individual [[thyroid follicular cell]]:<ref name="Elsevier/Saunders">{{cite book|title=Medical Physiology: A Cellular And Molecular Approaoch|vauthors=Boron WF, Boulpaep E|publisher=Elsevier/Saunders|year=2003|isbn=978-1-4160-2328-9|page=1300|chapter=Chapter 48: "synthesis of thyroid hormones"}}</ref>
<br />- [[Thyroglobulin]] is synthesized in the [[rough endoplasmic reticulum]] and follows the [[secretory pathway]] to enter the colloid in the lumen of the [[thyroid follicle]] by [[exocytosis]].
<br />- Meanwhile, a [[sodium-iodide symporter|sodium-iodide (Na/I) symporter]] pumps iodide (I<sup>−</sup>) [[active transport|actively]] into the cell, which previously has crossed the [[endothelium]] by largely unknown mechanisms. 
<br />- This iodide enters the follicular lumen from the cytoplasm by the transporter [[pendrin]], in a purportedly [[passive transport|passive]] manner.
<br />- In the colloid, iodide (I<sup>−</sup>) is [[Redox|oxidized]] to iodine (I<sup>0</sup>) by an enzyme called [[thyroid peroxidase]].
<br />- Iodine (I<sup>0</sup>) is very reactive and iodinates the thyroglobulin at [[Tyrosine|tyrosyl]] residues in its protein chain (in total containing approximately 120 tyrosyl residues).
<br />- In ''conjugation'', adjacent tyrosyl residues are paired together.
<br />- The entire complex re-enters the follicular cell by [[endocytosis]].
<br />- [[Proteolysis]] by various [[protease]]s liberates [[thyroxine]] and [[triiodothyronine]] molecules, which enters the blood by largely unknown mechanisms.
]]

The thyroid hormones are created from [[thyroglobulin]]. This is a [[protein]] within the colloid in the [[follicular lumen]] that is originally created within the [[rough endoplasmic reticulum]] of follicular cells and then transported into the follicular lumen. Thyroglobulin contains 123 units of [[tyrosine]], which reacts with iodine within the follicular lumen.<ref name="ACBianco">{{cite journal | vauthors = Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR | title = Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases | journal = Endocrine Reviews | volume = 23 | issue = 1 | pages = 38–89 | date = February 2002 | pmid = 11844744 | doi = 10.1210/edrv.23.1.0455 | doi-access = free }}</ref>

[[Iodine]] is essential for the production of the thyroid hormones. Iodine (I<sup>0</sup>) travels in the blood as [[iodide]] (I<sup>−</sup>), which is taken up into the follicular cells by a [[sodium-iodide symporter]]. This is an [[ion channel]] on the cell membrane which in the same action transports two sodium ions and an iodide ion into the cell.<ref name=williams>{{cite book| vauthors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM |title=Williams Textbook of Endocrinology |url= https://archive.org/details/williamstextbook00melm_993 |url-access=limited|date=2011|publisher=Saunders|page=[https://archive.org/details/williamstextbook00melm_993/page/n336 331]|isbn=978-1-4377-0324-5|edition=12th}}</ref> Iodide then travels from within the cell into the lumen, through the action of [[pendrin]], an iodide-chloride [[antiporter]]. In the follicular lumen, the iodide is then [[oxidation|oxidized]] to iodine. This makes it more reactive,<ref name="Elsevier/Saunders"/> and the iodine is attached to the active tyrosine units in thyroglobulin by the enzyme [[thyroid peroxidase]]. This forms the precursors of thyroid hormones [[monoiodotyrosine]] (MIT), and [[diiodotyrosine]] (DIT).<ref name=boron />

When the follicular cells are stimulated by [[thyroid-stimulating hormone]], the follicular cells reabsorb thyroglobulin from the follicular lumen. The iodinated tyrosines are cleaved, forming the thyroid hormones T<sub>4</sub>, T<sub>3</sub>, DIT, MIT, and traces of [[reverse triiodothyronine]]. T<sub>3</sub> and T<sub>4</sub> are released into the blood. The hormones secreted from the gland are about 80–90% T<sub>4</sub> and about 10–20% T<sub>3</sub>.<ref name="endocrine">[http://www.endocrineweb.com/thyfunction.html How Your Thyroid Works: A Delicate Feedback Mechanism]. Updated 2009-05-21.</ref><ref name="percent">[https://web.archive.org/web/20060614062534/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=endocrin.chapter.235 The thyroid gland] in ''Endocrinology: An Integrated Approach'' by Stephen Nussey and Saffron Whitehead (2001) Published by BIOS Scientific Publishers Ltd. {{ISBN|1-85996-252-1}}</ref> [[Deiodinase|Deiodinase enzymes]] in peripheral tissues remove the iodine from MIT and DIT and convert T<sub>4</sub> to T<sub>3</sub> and RT<sub>3.</sub><ref name="ACBianco" /> This is a major source of both RT<sub>3</sub> (95%) and T<sub>3</sub> (87%) in peripheral tissues.<ref>{{Cite book|title=Ganong's review of medical physiology Edition 25}}</ref>

===Regulation===

The production of thyroxine and triiodothyronine is primarily regulated by thyroid-stimulating hormone (TSH), released by the [[anterior pituitary]] gland. TSH release in turn is stimulated by [[thyrotropin releasing hormone]] (TRH), released in a pulsatile manner from the [[hypothalamus]].{{sfn|Greenspan's|2011|p=174}} The thyroid hormones provide [[negative feedback]] to the [[thyrotrope]]s TSH and TRH: when the thyroid hormones are high, TSH production is suppressed. This negative feedback also occurs when levels of TSH are high, causing TRH production to be suppressed.{{sfn|Greenspan's|2011|p=177}}

TRH is secreted at an increased rate in situations such as cold exposure in order to stimulate [[thermogenesis]].{{sfn|Guyton & Hall|2011|p=896}} In addition to being suppressed by the presence of thyroid hormones, TSH production is blunted by [[dopamine]], [[somatostatin]], and [[glucocorticoid]]s.{{sfn|Harrison's|2011|pp=2215}}

===Calcitonin===
{{Main|Calcitonin}}
The thyroid gland also produces the hormone [[calcitonin]], which helps regulate blood [[calcium metabolism|calcium]] levels. Parafollicular cells produce calcitonin in response to [[hypercalcemia|high blood calcium]]. Calcitonin decreases the release of calcium from bone, by decreasing the activity of [[osteoclast]]s, cells which break down bone. Bone is constantly reabsorbed by osteoclasts and created by [[osteoblast]]s, so calcitonin effectively stimulates movement of calcium into [[bone]]. The effects of calcitonin are opposite those of the [[parathyroid hormone]] (PTH) produced in the parathyroid glands. However, calcitonin seems far less essential than PTH, since calcium metabolism remains clinically normal after removal of the thyroid ([[thyroidectomy]]), but not the [[parathyroid gland]]s.{{sfn|Guyton & Hall|2011|pp=988–9}}

== Gene and protein expression ==
{{Further |Bioinformatics#Gene and protein expression}}
About 20,000 [[protein-coding gene]]s are expressed in human cells: 70% of these genes are expressed in thyroid cells.<ref>{{cite web|url=https://www.proteinatlas.org/humanproteome/thyroid+gland|title=The human proteome in thyroid gland – The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-09-25}}</ref><ref>{{cite journal | vauthors = Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F | s2cid = 802377 | display-authors = 6 | title = Proteomics. Tissue-based map of the human proteome | journal = Science | volume = 347 | issue = 6220 | article-number = 1260419 | date = January 2015 | pmid = 25613900 | doi = 10.1126/science.1260419 }}</ref> Two-hundred and fifty of these genes are more specifically expressed in the thyroid, and about 20 genes are highly thyroid specific. In the follicular cells, the proteins synthesized by these genes direct thyroid hormone synthesis—[[thyroglobulin]], [[Thyroid peroxidase|TPO]], and [[Iodotyrosine deiodinase|IYD]]; while in the parafollicular c-cells, they direct calcitonin synthesis—[[Calcitonin|CALCA]], and [[Calcitonin gene-related peptide|CALCB]].

== Clinical significance ==
[[General practitioner]]s, and [[internal medicine]] specialists play a role in identifying and monitoring the treatment of thyroid disease. [[Endocrinology|Endocrinologists]] and [[thyroidologist]]s are thyroid specialists. Thyroid surgeons or [[otolaryngologists]] are responsible for the surgical management of thyroid disease.

=== Functional disorders ===

====Hyperthyroidism====

{{Main|Hyperthyroidism}}
Excessive production of the thyroid hormones is called [[hyperthyroidism]]. Causes include [[Graves' disease]], [[toxic multinodular goitre]], solitary [[thyroid adenoma]], inflammation, and a [[pituitary adenoma]] which secretes excess TSH. Another cause is excess iodine availability, either from excess ingestion, induced by the drug [[amiodarone]], or following [[iodinated contrast]] [[medical imaging|imaging]].{{sfn|Davidson's|2010|p=738}}<ref>{{cite journal | vauthors = Rusandu A, Sjøvold BH, Hofstad E, Reidunsdatter RJ | title = Iodinated contrast media and their effect on thyroid function - Routines and practices among diagnostic imaging departments in Norway | journal = Journal of Medical Radiation Sciences | volume = 67 | issue = 2 | pages = 111–118 | date = June 2020 | pmid = 32232955 | pmc = 7276191 | doi = 10.1002/jmrs.390 }}</ref>

Hyperthyroidism often causes a variety of [[symptoms#Types|non-specific symptoms]] including weight loss, increased appetite, insomnia, decreased tolerance of heat, tremor, [[palpitations]], anxiety and nervousness. In some cases it can cause [[angina|chest pain]], [[Diarrhea|diarrhoea]], hair loss and muscle weakness.{{sfn|Davidson's|2010|p=740}} Such symptoms may be managed temporarily with drugs such as [[beta blocker]]s.{{sfn|Davidson's|2010|p=739}}

Long-term management of hyperthyroidism may include drugs that suppress thyroid function such as [[propylthiouracil]], [[carbimazole]] and [[methimazole]].{{sfn|Davidson's|2010|p=745}} Alternatively, [[Isotopes of iodine#Radioiodines 123I, 124I, 125I, and 131I in medicine and biology|radioactive iodine-131]] can be used to destroy thyroid tissue: radioactive iodine is selectively taken up by thyroid cells, which over time destroys them. The chosen [[first-line treatment]] will depend on the individual and on the country where being treated. [[Thyroidectomy|Surgery to remove the thyroid]] can sometimes be performed as a [[Natural orifice transluminal endoscopic surgery#State of research|transoral thyroidectomy]], a [[minimally invasive procedure]].<ref>{{cite journal | vauthors = Cury AN, Meira VT, Monte O, Marone M, Scalissi NM, Kochi C, Calliari LE, Longui CA | display-authors = 6 | title = Clinical experience with radioactive iodine in the treatment of childhood and adolescent Graves' disease | journal = Endocrine Connections | volume = 2 | issue = 1 | pages = 32–7 | date = March 2013 | pmid = 23781316 | pmc = 3680965 | doi = 10.1530/EC-12-0049 }}</ref> Surgery does however carry a risk of damage to the [[parathyroid gland]]s and the [[recurrent laryngeal nerve]], which innervates the [[vocal cords]]. If the entire thyroid gland is removed, hypothyroidism will inevitably result, and [[Thyroid hormone replacement|thyroid hormone substitutes]] will be needed.<ref>[http://www.medicinenet.com/script/main/art.asp?articlekey=54416 Thyroid Problems] eMedicine Health. Retrieved on 2010-02-07</ref>{{sfn|Davidson's|2010|p=739}}

====Hypothyroidism====

{{Main|Hypothyroidism}}
An underactive thyroid gland results in [[hypothyroidism]]. Typical symptoms are abnormal weight gain, tiredness, [[constipation]], [[heavy menstrual bleeding]], hair loss, cold intolerance, and [[bradycardia|a slow heart rate]].{{sfn|Davidson's|2010|p=740}} [[Iodine deficiency]] is the most common cause of hypothyroidism worldwide,<ref>{{cite news|title=Iodine Deficiency & Nutrition|url=https://www.thyroidfoundation.org.au/page/13/iodine-nutrition-iodine-deficiency|access-date=11 January 2017|work=www.thyroidfoundation.org.au|agency=Australian Thyroid Foundation|archive-url=https://web.archive.org/web/20170113111929/https://www.thyroidfoundation.org.au/page/13/iodine-nutrition-iodine-deficiency|archive-date=13 January 2017}}</ref> and the autoimmune disease [[Hashimoto's thyroiditis]] is the most common cause in the developed world.<ref>{{cite web|last1=So|first1=Michelle|last2=MacIsaac|first2=Richard|last3=Grossmann|first3=Mathis | name-list-style = vanc |title=Hypothyroidism – Investigation and management |url= http://www.racgp.org.au/afp/2012/august/hypothyroidism/ |website=www.racgp.org.au|publisher=The Royal Australian College of General Practitioners|access-date=11 January 2017|language=en}}</ref> Other causes include congenital abnormalities, diseases causing transient inflammation, surgical removal or radioablation of the thyroid, the drugs [[amiodarone]] and [[lithium]], [[amyloidosis]], and [[sarcoidosis]].{{sfn|Davidson's|2010|p=741}} Some forms of hypothyroidism can result in [[myxedema]] and severe cases can result in [[myxedema coma]].{{sfn|Davidson's|2010|p=743}}

Hypothyroidism is managed with replacement of the [[thyroid hormones]]. This is usually given daily as an oral supplement, and may take a few weeks to become effective.{{sfn|Davidson's|2010|p=743}} Some causes of hypothyroidism, such as [[Postpartum thyroiditis]] and [[Subacute thyroiditis]] may be transient and pass over time, and other causes such as iodine deficiency may be able to be rectified with dietary supplementation.{{sfn|Davidson's|2010|p=741-3}}

===Diseases===
====Graves' disease====
{{main|Graves' disease}}
[[Graves' disease]] is an autoimmune disorder that is the most common cause of hyperthyroidism.<ref name=":0">{{cite journal | vauthors = Smith TJ, Hegedüs L | title = Graves' Disease | language = EN | journal = The New England Journal of Medicine | volume = 375 | issue = 16 | pages = 1552–1565 | date = October 2016 | pmid = 27797318 | doi = 10.1056/nejmra1510030 | url = https://findresearcher.sdu.dk:8443/ws/files/128446579/Graves_Disease.pdf | access-date = 2020-07-22 | archive-date = 2020-08-01 | archive-url = https://web.archive.org/web/20200801093036/https://findresearcher.sdu.dk:8443/ws/files/128446579/Graves_Disease.pdf }}</ref> In Graves' disease, for an unknown reason [[autoantibody|autoantibodies]] develop against the thyroid stimulating hormone receptor. These antibodies activate the receptor, leading to development of a goitre and symptoms of hyperthyroidism, such as heat intolerance, weight loss, diarrhoea and palpitations. Occasionally such antibodies block but do not activate the receptor, leading to symptoms associated with hypothyroidism.<ref name=":0" /> In addition, gradual protrusion of the eyes may occur, called [[Graves' ophthalmopathy]], as may swelling of the front of the shins.<ref name=":0" /> Graves' disease can be diagnosed by the presence of [[pathognomonic]] features such as involvement of the eyes and shins, or isolation of autoantibodies, or by results of a radiolabelled uptake scan. Graves' disease is treated with anti-thyroid drugs such as propylthiouracil, which decrease the production of thyroid hormones, but hold a high rate of relapse. If there is no involvement of the eyes, then use of radioactive isotopes to ablate the gland may be considered. Surgical removal of the gland with subsequent thyroid hormone replacement may be considered, however this will not control symptoms associated with the eye or skin.<ref name=":0" />

====Nodules====

{{Main|Thyroid nodule}}
[[Thyroid nodule]]s are often found on the gland, with a [[prevalence]] of 4–7%.<ref name="Dean2008">{{cite journal | vauthors = Dean DS, Gharib H | title = Epidemiology of thyroid nodules | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 22 | issue = 6 | pages = 901–11 | date = December 2008 | pmid = 19041821 | doi = 10.1016/j.beem.2008.09.019 }}</ref> The majority of nodules do not cause any symptoms, thyroid hormone secretion is normal, and they are non-cancerous.<ref name="Orlov2003">{{cite journal | vauthors = Welker MJ, Orlov D | title = Thyroid nodules | journal = American Family Physician | volume = 67 | issue = 3 | pages = 559–66 | date = February 2003 | pmid = 12588078 | url = http://www.aafp.org/afp/2003/0201/p559.html | access-date = 6 September 2016 }}</ref> Non-cancerous cases include simple [[cyst]]s, [[colloid nodule]]s, and [[thyroid adenoma]]s. Malignant nodules, which only occur in about 5% of nodules, include [[Follicular thyroid cancer|follicular]], [[Papillary thyroid cancer|papillary]], [[Medullary thyroid cancer|medullary]] carcinomas and [[metastasis]] from other sites.{{sfn|Davidson's|2010|p=744}} Nodules are more likely in females, those who are exposed to radiation, and in those who are iodine deficient.<ref name="Dean2008" />

When a nodule is present, [[thyroid function test]]s determine whether the nodule is secreting excess thyroid hormones, causing hyperthyroidism.<ref name="Orlov2003" /> When the thyroid function tests are normal, an [[medical ultrasound|ultrasound]] is often used to investigate the nodule, and provide information such as whether the nodule is fluid-filled or a solid mass, and whether the appearance is suggestive of a benign or malignant cancer.<ref name="Dean2008" /> A [[needle aspiration biopsy]] may then be performed, and the sample undergoes [[cytology]], in which the appearance of cells is viewed to determine whether they resemble normal or cancerous cells.{{sfn|Davidson's|2010|p=744}}

The presence of multiple nodules is called a [[multinodular goitre]]; and if it is associated with hyperthyroidism, it is called a [[toxic multinodular goitre]].{{sfn|Davidson's|2010|p=744}}

====Goitre====

{{main|Goitre}}
An enlarged thyroid gland is called a [[goitre]].<ref>{{cite web|title=goitre – definition of goitre in English|url=https://en.oxforddictionaries.com/definition/goitre|archive-url=https://web.archive.org/web/20160918233214/https://en.oxforddictionaries.com/definition/goitre|archive-date=September 18, 2016|website=Oxford Dictionaries {{!}} English|access-date=18 September 2016}}</ref> Goitres are present in some form in about 5% of people,{{sfn|Davidson's|2010|p=744}} and are the result of a large number of causes, including iodine deficiency, [[autoimmune disease]] (both Graves' disease and Hashimoto's thyroiditis), infection, inflammation, and infiltrative disease such as [[sarcoidosis]] and [[amyloidosis]]. Sometimes no cause can be found, a state called "simple goitre".{{sfn|Davidson's|2010|p=750}}

Some forms of goitre are associated with pain, whereas many do not cause any symptoms. Enlarged goitres may extend beyond the normal position of the thyroid gland to below the sternum, around the airway or esophagus.{{sfn|Davidson's|2010|p=744}} Goitres may be associated with hyperthyroidism or hypothyroidism, relating to the underlying cause of the goitre.{{sfn|Davidson's|2010|p=744}} Thyroid function tests may be done to investigate the cause and effects of the goitre. The underlying cause of the goitre may be treated, however many goitres with no associated symptoms are [[Watchful waiting|simply monitored]].{{sfn|Davidson's|2010|p=744}}

====Inflammation====
{{Main|Thyroiditis}}
Inflammation of the thyroid is called [[thyroiditis]], and may cause symptoms of hyperthyroidism or hypothyroidism. Two types of thyroiditis initially present with hyperthyroidism and are sometimes followed by a period of hypothyroidism – Hashimoto's thyroiditis and [[postpartum thyroiditis]]. There are other disorders that cause inflammation of the thyroid, and these include [[subacute thyroiditis]], [[acute thyroiditis]], [[silent thyroiditis]], [[Riedel's thyroiditis]] and traumatic injury, including [[palpation thyroiditis]].{{sfn|Harrison's|2011|pp=2237}}

[[Hashimoto's thyroiditis]] is an [[autoimmune disorder]] in which the thyroid gland is infiltrated by the [[lymphocyte]]s [[B cell]] and [[T cell]]s. These progressively destroy the thyroid gland.{{sfn|Harrison's|2011|pp=2230}} In this way, Hasimoto's thyroiditis may have occurred insidiously, and only be noticed when thyroid hormone production decreases, causing symptoms of hypothyroidism.{{sfn|Harrison's|2011|pp=2230}} Hashimoto's is more common in females than males, much more common after the age of 60, and has known genetic risk factors.{{sfn|Harrison's|2011|pp=2230}} Also more common in individuals with Hashimoto's thyroiditis are [[Type 1 diabetes]], [[pernicious anaemia]], [[Addison's disease]], and [[vitiligo]].{{sfn|Harrison's|2011|pp=2230}}

[[Postpartum thyroiditis]] occurs sometimes following [[childbirth]]. After delivery, the thyroid becomes inflamed and the condition initially presents with a period of hyperthyroidism followed by hypothyroidism and, usually, a return to normal function.{{sfn|Harrison's|2011|pp=2238}} The course of the illness takes place over several months, and is characterised by a painless goitre. Antibodies against thyroid peroxidase can be found on testing. The inflammation usually resolves without treatment, although thyroid hormone replacement may be needed during the period of hypothyroidism.{{sfn|Harrison's|2011|pp=2238}}

====Cancer====
{{main|Thyroid cancer}}
The most common [[tumor]] affecting the thyroid is a benign [[thyroid adenoma|adenoma]], usually presenting as a painless mass in the neck.{{sfn|Harrison's|2011|p=2242}} [[Thyroid cancer]]s are most often [[carcinoma]]s, although cancer can occur in any tissue that the thyroid consists of, including cancer of C-cells and lymphomas. Cancers from other sites also rarely lodge in the thyroid.{{sfn|Harrison's|2011|p=2242}} Radiation of the head and neck presents a [[Risk factor (epidemiology)|risk factor]] for thyroid cancer, and cancer is more common in women than men, occurring at a rate of about 2:1.{{sfn|Harrison's|2011|p=2242}}

In most cases, thyroid cancer presents as a painless mass in the neck. It is very unusual for thyroid cancers to present with other symptoms, although in some cases cancer may cause hyperthyroidism.{{sfn|Davidson's|2010|p=751}} Most thyroid cancers are [[Papillary thyroid cancer|papillary]], followed by [[Follicular thyroid cancer|follicular]], [[Medullary thyroid cancer|medullary]], and [[thyroid lymphoma]].{{sfn|Harrison's|2011|p=2242}}{{sfn|Davidson's|2010|p=751}} Because of the prominence of the thyroid gland, cancer is often detected earlier in the course of disease as the cause of a nodule, which may undergo [[fine-needle aspiration]]. Thyroid function tests will help reveal whether the nodule produces excess thyroid hormones. A [[radioactive iodine uptake test]] can help reveal the activity and location of the cancer and metastases.{{sfn|Harrison's|2011|p=2242}}{{sfn|Davidson's|2010|p=752}}

Thyroid cancers are treated by [[thyroidectomy|removing the whole or part of thyroid gland]]. Radioactive [[Iodine-131]] may be given to [[Radiofrequency ablation|radioablate]] the thyroid. [[Thyroxine]] is given to replace the hormones lost and to suppress TSH production, as TSH may stimulate recurrence.{{sfn|Davidson's|2010|p=752}} With the exception of the rare [[anaplastic thyroid cancer]], which carries a very poor prognosis, most thyroid cancers carry an excellent prognosis and can even be considered curable.{{sfn|Harrison's|2011|p=2242,2246}}

====Congenital====
A [[persistent thyroglossal duct]] is the most common clinically significant [[birth defect]] of the thyroid gland. A persistent sinus tract may remain as a vestigial remnant of the tubular development of the thyroid gland. Parts of this tube may be obliterated, leaving small segments to form [[thyroglossal cyst]]s.<ref name="LANGMAN" /> Preterm neonates are at risk of hypothyroidism as their thyroid glands are insufficiently developed to meet their postnatal needs.<ref>{{cite journal | vauthors = Berbel P, Navarro D, Ausó E, Varea E, Rodríguez AE, Ballesta JJ, Salinas M, Flores E, Faura CC, de Escobar GM | display-authors = 6 | title = Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity | journal = Cerebral Cortex | volume = 20 | issue = 6 | pages = 1462–75 | date = June 2010 | pmid = 19812240 | pmc = 2871377 | doi = 10.1093/cercor/bhp212 | url = }}</ref> In order to detect hypothyroidism in newborn babies, to prevent growth and development abnormalities in later life, many countries have [[newborn screening]] programs at birth.<ref>{{cite journal | vauthors = Büyükgebiz A | title = Newborn screening for congenital hypothyroidism | journal = Journal of Clinical Research in Pediatric Endocrinology | volume = 5 Suppl 1 | issue = 4 | pages = 8–12 | date = 15 November 2012 | pmid = 23154158 | pmc = 3608007 | doi = 10.4274/Jcrpe.845 }}</ref>

Infants with thyroid hormone deficiency ([[congenital hypothyroidism]]) can manifest problems of physical growth and development as well as brain development, termed [[cretinism]].{{sfn|Greenspan's|2011|p=164}}<ref name=":1" /> Children with congenital hypothyroidism are treated supplementally with [[levothyroxine]], which facilitates normal growth and development.<ref>{{cite journal | vauthors = Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK | title = Update of newborn screening and therapy for congenital hypothyroidism | journal = Pediatrics | volume = 117 | issue = 6 | pages = 2290–303 | date = June 2006 | pmid = 16740880 | doi = 10.1542/peds.2006-0915 | doi-access = free | author5 = Public Health Committee | author6 = Lawson Wilkins Pediatric Endocrine Society | author3 = American Thyroid Association }}</ref>

Mucinous, clear secretions may collect within these cysts to form either spherical masses or fusiform swellings, rarely larger than 2 to 3&nbsp;cm in diameter. These are present in the midline of the [[neck]] anterior to the [[trachea]]. Segments of the duct and cysts that occur high in the neck are lined by [[stratified squamous epithelium]], which is essentially identical to that covering the posterior portion of the [[tongue]] in the region of the foramen cecum. The disorders that occur in the lower neck more proximal to the thyroid gland are lined by epithelium resembling the thyroidal acinar epithelium. Characteristically, next to the lining epithelium, there is an intense lymphocytic infiltrate. [[superinfection|Superimposed infection]] may convert these lesions into abscess cavities, and rarely, give rise to cancers.{{citation needed|date=September 2011}}

Another disorder is that of [[thyroid dysgenesis]] which can result in various presentations of one or more [[ectopia (medicine)|misplaced]] accessory thyroid glands.{{sfn|Gray's Anatomy|2008|pp=462–4}} These can be asymptomatic.

====Iodine====
{{Further|Iodine in biology}}
[[File:The thyroid gland in health and disease (1917) (14780980651).jpg|thumb|Child affected by [[Congenital iodine deficiency syndrome]], associated with a lack of iodine.<ref>The thyroid gland in health and disease Year: 1917 [[Robert McCarrison]]</ref>]]
[[Iodine deficiency]], most common in inland and mountainous areas, can predispose to goitre – if widespread, known as [[endemic goitre]].{{sfn|Greenspan's|2011|p=164}} Pregnant women deficient of iodine can give birth to infants with thyroid hormone deficiency.{{sfn|Greenspan's|2011|p=164}}<ref name=":1" /> The use of [[iodised salt]] to add iodine to the diet<ref name=":1" /> has eliminated [[endemic cretinism]] in most developed countries,<ref>{{Cite book|url=https://books.google.com/books?id=sX-HCgAAQBAJ&q=iodine+supplementation+has+eliminated+cretinism&pg=PA268|title=Global Epidemiology of Cancer|last=Harris|first=Randall E. | name-list-style = vanc |date=2015-05-07|publisher=Jones & Bartlett Publishers|isbn=978-1-284-03445-5|page=268|language=en}}</ref> and over 120 countries have made the iodination of [[salt]] mandatory.<ref>{{cite journal | vauthors = Leung AM, Braverman LE, Pearce EN | title = History of U.S. iodine fortification and supplementation | journal = Nutrients | volume = 4 | issue = 11 | pages = 1740–6 | date = November 2012 | pmid = 23201844 | pmc = 3509517 | doi = 10.3390/nu4111740 | doi-access = free }}</ref><ref name=Map>{{cite web|url=https://fortificationdata.org/map-number-of-nutrients/|title=Map: Count of Nutrients In Fortification Standards|website=Global Fortification Data Exchange|access-date=23 December 2019}}</ref>

Because the thyroid concentrates iodine, it also concentrates the various radioactive [[isotope]]s of iodine produced by [[nuclear fission]]. In the event of large accidental releases of such material into the environment, the uptake of radioactive iodine isotopes by the thyroid can, in theory, be blocked by saturating the uptake mechanism with a large surplus of [[Radiation pill|non-radioactive iodine]], taken in the form of potassium iodide tablets. One consequence of the [[Chernobyl disaster]] was an increase in [[thyroid cancer]]s in children in the years following the accident.<ref>{{cite news| url=https://news.bbc.co.uk/2/hi/science/nature/1319386.stm | work=BBC News | title=Chernobyl children show DNA changes | date=2001-05-08 | access-date=2010-05-25}}</ref>

Excessive iodine intake is uncommon and usually has no effect on the thyroid function. Sometimes though it may cause hyperthyroidism, and sometimes hypothyroidism with a resulting goitre.<ref name="MSD">{{cite web |title=Iodine - Disorders of Nutrition |url=https://www.msdmanuals.com/en-gb/home/disorders-of-nutrition/minerals/iodine |website=MSD Manual Consumer Version |access-date=18 December 2019 |archive-date=18 December 2019 |archive-url=https://web.archive.org/web/20191218133539/https://www.msdmanuals.com/en-gb/home/disorders-of-nutrition/minerals/iodine }}</ref>

===Evaluation===
The thyroid is [[Medical examination|examined]] by observation of the gland and surrounding neck for swelling or enlargement.<ref name=Clinical_examination /> It is then [[palpation|felt]], usually from behind, and a person is often asked to swallow to better feel the gland against the fingers of the examiner.<ref name=Clinical_examination /> The gland moves up and down with swallowing because of its attachments to the thyroid and cricoid cartilages.{{sfn|Elsevier's|2007|p=342}} In a healthy person the gland is not visible yet is [[palpation|palpable]] as a soft mass. Examination of the thyroid gland includes the search for abnormal masses and the assessment of overall thyroid size.<ref>{{cite book |title=Illustrated Anatomy of the Head and Neck |last1=Fehrenbach |last2=Herring |publisher=Elsevier |year=2012 |page=158 |isbn=978-1-4377-2419-6 }}</ref> The character of the thyroid, swellings, nodules, and their consistency may all be able to be felt. If a goitre is present, an examiner may also feel down the neck consider [[Percussion (medicine)|tapping]] the upper part of the chest to check for extension. Further tests may include raising the arms ([[Pemberton's sign]]), listening to the gland with a [[stethoscope]] for [[bruit]]s, testing of reflexes, and palpation of the lymph nodes in the head and neck. 

An examination of the thyroid will also include observation of the person as a whole, to look for systemic signs such as weight gain or loss, hair loss, and signs in other locations – such as protrusion of the eyes or swelling of the calves in Graves' disease.{{sfn|Harrison's|2011|p=2228}}<ref name=Clinical_examination>{{Cite book|title=Clinical Examination|last=Talley|first=Nicholas | name-list-style = vanc |publisher=Churchill Livingstone|year=2014|isbn=978-0-7295-4198-5|pages=Chapter 28. "The endocrine system". pp 355–362}}</ref>

===Tests===
[[Thyroid function test]]s include a battery of [[blood test]]s, including the measurement of the thyroid hormones, as well as the measurement of thyroid stimulating hormone (TSH).{{sfn|Greenspan's|2011|p=184}} They may reveal hyperthyroidism (high T<sub>3</sub> and T<sub>4</sub>), hypothyroidism (low T<sub>3</sub>, T<sub>4</sub>), or subclinical hyperthyroidism (normal T<sub>3</sub> and T<sub>4</sub> with a low TSH).{{sfn|Greenspan's|2011|p=184}}

TSH levels are considered the most sensitive marker of thyroid dysfunction.{{sfn|Greenspan's|2011|p=184}} They are however not always accurate, particularly if the cause of hypothyroidism is thought to be related to insufficient [[thyrotropin releasing hormone]] (TRH) secretion, in which case it may be low or falsely normal. In such a case a TRH stimulation test, in which TRH is given and TSH levels are measured at 30 and 60-minutes after, may be conducted.{{sfn|Greenspan's|2011|p=184}}

T<sub>3</sub> and T<sub>4</sub> can be measured directly. However, as the two thyroid hormones travel bound to other molecules, and it is the "free" component that is biologically active, free T<sub>3</sub> and free T<sub>4</sub> levels can be measured.{{sfn|Greenspan's|2011|p=184}} T<sub>3</sub> is preferred, because in hypothyroidism T<sub>3</sub> levels may be normal.{{sfn|Greenspan's|2011|p=184}} The ratio of bound to unbound thyroid hormones is known as the thyroid hormone binding ratio (THBR).{{sfn|Harrison's|2011|p=2229}} It is also possible to measure directly the main carriers of the thyroid hormones, thyroglobulin and throxine-binding globulin.{{sfn|Greenspan's|2011|p=186}} Thyroglobulin will also be measurable in a healthy thyroid, and will increase with inflammation, and may also be used to measure the success of thyroid removal or ablation. If successful, thyroglobulin should be undetectable.{{sfn|Harrison's|2011|p=2229}} Lastly, antibodies against components of the thyroid, particularly anti-TPO and anti-thyroglobulin, can be measured. These may be present in normal individuals but are highly [[Psychic|sensitive]] for autoimmune-related disease.{{sfn|Harrison's|2011|p=2229}}

====Imaging====
Ultrasound of the thyroid may be used to reveal whether structures are solid or filled with fluid, helping to differentiate between nodules and goitres and cysts. It may also help differentiate between malignant and benign lesions.{{sfn|Greenspan's|2011|p=189}} 

When further imaging is required, a radiolabelled [[iodine-123]] or [[technetium-99]] uptake scan may take place. This can determine the size and shape of lesions, reveal whether nodules or goitres are metabolically active, and reveal and monitor sites of thyroid disease or cancer deposits [[metastases|outside the thyroid]].{{sfn|Greenspan's|2011|p=188-9}}

A [[fine needle aspiration]] of a sample of thyroid tissue may be taken in order to evaluate a lesion seen on ultrasound which is then sent for [[histopathology]] and [[cytology]].{{sfn|Greenspan's|2011|p=190}}

[[Computed tomography of the thyroid]] plays an important role in the evaluation of thyroid cancer.<ref name=Saeedan2016>{{cite journal | vauthors = Bin Saeedan M, Aljohani IM, Khushaim AO, Bukhari SQ, Elnaas ST | title = Thyroid computed tomography imaging: pictorial review of variable pathologies | journal = Insights into Imaging | volume = 7 | issue = 4 | pages = 601–17 | date = August 2016 | pmid = 27271508 | pmc = 4956631 | doi = 10.1007/s13244-016-0506-5 }} [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License]</ref> CT scans often [[Incidental imaging finding|incidentally find]] thyroid abnormalities, and thereby practically becomes the first investigation modality.<ref name=Saeedan2016/>

==History==
[[File:Thespiae 431-424 BC.jpg|thumb|right|The thyroid was named by [[Thomas Wharton (anatomist)|Thomas Wharton]] after the ancient Greek shield of a similar pronunciation. Shown is an example of such a shield, as engraved on a [[obol (coin)|coin dating from 431 to 424 BCE]].]]

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

===Antiquity===
The presence and diseases of the thyroid have been noted and treated for thousands of years.<ref name="timeline">{{cite web |title=Thyroid History Timeline – American Thyroid Association |url=http://www.thyroid.org/about-american-thyroid-association/clark-t-sawin-history-resource-center/thyroid-history-timeline/ |access-date=13 November 2016 |website=www.thyroid.org |archive-date=3 August 2021 |archive-url=https://web.archive.org/web/20210803202257/https://www.thyroid.org/about-american-thyroid-association/clark-t-sawin-history-resource-center/thyroid-history-timeline/ }}</ref>  In 1600 BCE burnt [[sponge]] and [[seaweed]] (which contain iodine) were used within China for the treatment of goitres, a practice which has developed in many parts of the world.<ref name="timeline" /><ref name=":2" /> In [[Ayurveda|Ayurvedic medicine]], the book [[Sushruta Samhita]] written about 1400 BCE described hyperthyroidism, hypothyroidism and goitre.<ref name=":2">{{cite journal | vauthors = Niazi AK, Kalra S, Irfan A, Islam A | title = Thyroidology over the ages | journal = Indian Journal of Endocrinology and Metabolism | volume = 15 | issue = Suppl 2 | pages = S121-6 | date = July 2011 | pmid = 21966648 | pmc = 3169859 | doi = 10.4103/2230-8210.83347 | doi-access = free }}</ref> [[Aristotle]] and [[Xenophon]] in the fifth century BCE describe cases of [[diffuse toxic goitre]].<ref name=":2" /> Hippocrates and Plato in the fourth century BCE provided some of the first descriptions of the gland itself, proposing its function as a salivary gland.<ref name=":2" /> [[Pliny the Elder]] in the first century BCE referred to epidemics of goitre in the [[Alps]] and proposed treatment with burnt seaweed,<ref name="timeline" /> a practice also referred to by [[Galen]] in the second century, referred to burnt sponge for the treatment of goitre.<ref name="timeline" /> The [[Chinese language|Chinese]] [[pharmacological|pharmacology]] text ''[[Shennong Ben Cao Jing]]'', written ca. 200–250, also refers to goitre.<ref name="timeline" /><ref name=":2" />

===Scientific era===
In 1500 [[polymath]] [[Leonardo da Vinci]] provided the first illustration of the thyroid.<ref name="timeline" /> In 1543 anatomist [[Andreas Vesalius]] gave the first anatomic description and illustration of the gland.<ref name="timeline" /> In 1656 the thyroid received its modern name, by the anatomist [[Thomas Wharton (anatomist)|Thomas Wharton]].<ref name="timeline" /> The gland was named thyroid, meaning shield, as its shape resembled the shields commonly used in Ancient Greece.<ref name="timeline" /> The English name ''thyroid gland''<ref name="Dorland">{{cite book | vauthors = Anderson DM | date = 2000 | title = Dorland's Illustrated Medical Dictionary | edition = 29th| location = Philadelphia/London/Toronto/Montreal/Sydney/Tokyo | publisher = W.B. Saunders Company }}</ref> is derived from the [[Contemporary Latin|medical Latin]] used by Wharton – {{Lang|la|glandula thyreoidea}}.<ref name="His">{{cite book | vauthors = His W | date = 1895 | title = Die anatomische Nomenclatur. Nomina Anatomica. Der von der Anatomischen Gesellschaft auf ihrer IX. Versammlung in Basel angenommenen Namen | trans-title = The anatomical nomenclature. Nominal Anatomica. Anatomical Society on its IX. Assembly adopted in Basel | language = de | location = Leipzig | publisher = Verlag Veit & Comp }}</ref> {{Lang|la|Glandula}} means 'gland' in Latin,<ref name="Lewis & Short">{{cite book | vauthors = Lewis CT, Short C | date = 1879 | title = A Latin dictionary. founded on Andrews' edition of Freund's Latin dictionary. | location = Oxford | publisher = Clarendon Press }}</ref> and {{Lang|la|thyreoidea}} can be traced back to the [[Ancient Greek]] word {{Lang|grc|θυρεοειδής}}, meaning 'shield-like/shield-shaped'.<ref name="Liddell & Scott">{{cite book | vauthors = Liddell HG, Scott R | date = 1940 | title = A Greek-English Lexicon. revised and augmented throughout by Sir Henry Stuart Jones. with the assistance of. Roderick McKenzie | location = Oxford | publisher = Clarendon Press }}</ref>

French chemist [[Bernard Courtois]] discovered iodine in 1811,<ref name=":2" /> and in 1896 [[Eugen Baumann]] documented it as the central ingredient in the thyroid gland. He did this by boiling the thyroid glands of a thousand sheep, and named the precipitate, a combination of the thyroid hormones, 'iodothyrin'.<ref name=":2" /> [[David Marine]] in 1907 proved that iodine is necessary for thyroid function.<ref name=":2" /><ref name="timeline" />  

Graves' disease was described by [[Robert James Graves]] in 1834. The role of the thyroid gland in metabolism was demonstrated in 1895 by [[Adolf Magnus-Levy]].<ref>{{cite journal | vauthors = Freake HC, Oppenheimer JH | title = Thermogenesis and thyroid function | journal = Annual Review of Nutrition | volume = 15 | issue = 1 | pages = 263–91 | date = 1995 | pmid = 8527221 | doi = 10.1146/annurev.nu.15.070195.001403 }}</ref> Thyroxine was first isolated in 1914 and synthesized in 1927, and triiodothyroxine in 1952.<ref name=":2" /><ref>{{cite web|url=http://www.medscape.com/viewarticle/433848|title=The thyroid glands: a brief historical perspective|last=Hamdy|first=Roland|website=www.medscape.com|access-date=2016-11-13}}</ref> The conversion of T<sub>4</sub> to T<sub>3</sub> was discovered in 1970.<ref name="timeline" /> The process of discovering TSH took place over the early to mid twentieth century.<ref>{{cite journal | vauthors = Magner J | title = Historical note: many steps led to the 'discovery' of thyroid-stimulating hormone | journal = European Thyroid Journal | volume = 3 | issue = 2 | pages = 95–100 | date = June 2014 | pmid = 25114872 | pmc = 4109514 | doi = 10.1159/000360534 }}</ref> TRH was discovered by Polish endocrinologist [[Andrew Schally]] in 1970, contributing in part to his Nobel Prize in Medicine in 1977.<ref name="timeline" /><ref>{{cite web|title=The Nobel Prize in Physiology or Medicine 1977|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1977/|website=www.nobelprize.org|access-date=14 January 2017}}</ref>

In the nineteenth century numerous authors described both [[cretinism]] and [[myxedema]], and their relationship to the thyroid.<ref name=":2" /> Charles Mayo coined the term hyperthyroidism in 1910.<ref name="timeline" /> [[Hakaru Hashimoto]] documented a case of Hashimoto's thyroiditis in 1912, [[autoantibody|antibodies]] in this disease were demonstrated in 1956.<ref name=":2" /> Knowledge of the thyroid and its conditions developed throughout the late nineteenth and twentieth centuries, with many modern treatments and investigative modalities evolving throughout the mid twentieth century, including the use of radioactive iodine, thiouracil and fine needle aspiration.<ref name="timeline" />

===Surgery===
Either [[Aëtius of Amida|Aetius]] in the sixth century CE<ref name=":2" /> or Persian [[Ali ibn Abbas al-Magusi]] in 990 CE conducted the first recorded thyroidectomy as a treatment for goitre.<ref name="timeline" /><ref name=":3">{{cite web|url=http://www.hormones.gr/115/article/article.html|title=Hormones.gr|last=Slidescenter.com|website=www.hormones.gr|access-date=2016-11-13}}</ref> Operations remained risky and generally were not successful until the 19th century, when descriptions emerged from a number of authors including Prussian surgeon [[Theodor Billroth]], Swiss surgeon and physiologist [[Theodor Kocher]], American physician [[Charles Horace Mayo|Charles Mayo]], American surgeons [[William Halsted]] and [[George Washington Crile|George Crile]]. These descriptions provided the basis for modern thyroid surgery.<ref>{{cite book|last1=Werner|first1=Sidney C.|last2=Ingbar|first2=Sidney H.|last3=Braverman|first3=Lewis E.|last4=Utiger|first4=Robert D. | name-list-style = vanc |title=Werner & Ingbar's the Thyroid: A Fundamental and Clinical Text|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-5047-9|page=387|url=https://books.google.com/books?id=HoOm6PuNcwwC&q=thyroid+gland+2700BC&pg=PA387|language=en|year=2005}}</ref> [[Theodor Kocher]] went on to win the [[Nobel Prize in Physiology or Medicine]] in 1909 "for his work on the physiology, pathology and surgery of the thyroid gland".<ref>{{cite web
 | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1909/index.html
 | title = The Nobel Prize in Physiology or Medicine 1909
 | access-date = 2007-07-28
 | publisher = Nobel Foundation
}}</ref>

==Other animals==
[[File:The thyroid gland in health and disease (1917) (14780977681).jpg|thumb|Goat affected by a [[goitre]]]]
The thyroid gland is found in all [[vertebrate]]s. In fish, it is usually located below the gills and is not always divided into distinct lobes. However, in some [[teleost]]s, patches of thyroid tissue are found elsewhere in the body, associated with the kidneys, spleen, heart, or eyes.<ref name=VB>{{Cite book| last1 = Romer | first1 = Alfred Sherwood | last2 = Parsons | first2 = Thomas S. | name-list-style = vanc | year=1977 |title=The Vertebrate Body |publisher=Holt-Saunders International |location= Philadelphia, PA|pages= 555–556|isbn= 978-0-03-910284-5}}</ref>

In [[tetrapod]]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. However, there is only ever a single thyroid gland in most [[mammal]]s, and the shape found in humans is common to many other species.<ref name=VB/>

In larval [[lamprey]]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]]s and [[amphioxi]] (lancelets), have a structure very similar to that of larval lampreys (the [[endostyle]]), and this also secretes iodine-containing compounds, though not thyroxine.<ref name=VB/>

Thyroxine is critical to [[metabolic regulation]], and growth throughout the vertebrate clade. Iodine and T<sub>4</sub> trigger the [[metamorphosis|change]] from a plant-eating water-dwelling [[tadpole]] into a meat-eating land-dwelling [[frog]], with better neurological, visuospatial, smell and cognitive abilities for hunting, as seen in other predatory animals. A similar phenomenon happens in the [[neotenic]] amphibian [[salamanders]], which, without introducing iodine, do not transform into land-dwelling adults, and live and reproduce in the larval form of aquatic [[axolotl]]. Among [[amphibian]]s, administering a thyroid-blocking agent such as [[propylthiouracil]] (PTU) can prevent tadpoles from metamorphosing into frogs; in contrast, administering thyroxine will trigger metamorphosis. In amphibian metamorphosis, thyroxine and iodine also exert a well-studied experimental model of [[apoptosis]] on the cells of gills, tail, and fins of tadpoles. Iodine, via iodolipids, has favored the evolution of terrestrial animal species and has likely played a crucial role in the [[evolution]] of the human brain.<ref>{{Cite journal| last = Venturi | first = Sebastiano | name-list-style = vanc |title=Evolutionary Significance of Iodine|journal=Current Chemical Biology|volume=5 |pages=155–162|year=2011|issn=1872-3136|doi=10.2174/187231311796765012|issue=3 | doi-broken-date = 18 July 2025 }}</ref><ref>{{Cite journal| last = Venturi | first = Sebastiano | name-list-style = vanc |title=Iodine, PUFAs and Iodolipids in Health and Disease: An Evolutionary Perspective|journal=Human Evolution|volume= 29 |issue= 1–3|pages=185–205|year=2014|issn=0393-9375}}</ref>

== See also ==
* [[Desiccated thyroid]]
* [[Thyroid disease in pregnancy]]

== References ==
{{Reflist|30em}}

===Books===
{{refbegin}}
* {{cite book | veditors = Greer MA | date = 1990 | title = The Thyroid Gland | series = Comprehensive Endocrinology Revised Series | publisher = Raven Press | location = N.Y. | isbn = 0-88167-668-3 }}
* {{cite book|last1=Shoback|first1=Dolores|editor-first1 = David G. | editor-last1 = Gardner | name-list-style = vanc |title=Greenspan's basic & clinical endocrinology|date=2011|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-162243-1|edition=9th| ref={{harvid|Greenspan's|2011}}}}
* {{cite book| first1 = John Edward | last1 = Hall | first2 = Arthur C | last2 = Guyton | name-list-style = vanc |title=Guyton and Hall textbook of medical physiology|year=2011|publisher=Saunders/Elsevier|location=Philadelphia, Pa.|isbn=978-1-4160-4574-8|edition=12th| ref={{harvid|Guyton & Hall|2011}}}}
* {{cite book|last1=Longo|first1=Dan|last2=Fauci|first2=Anthony|last3=Kasper|first3=Dennis|last4=Hauser|first4=Stephen|last5=Jameson|first5=J.|last6=Loscalzo|first6=Joseph | name-list-style = vanc |title=Harrison's Principles of Internal Medicine|date=August 11, 2011|publisher=McGraw-Hill Professional|isbn=978-0-07-174889-6|edition=18|ref={{harvid|Harrison's|2011}}}}
* {{cite book |editor-first1 = Nicki R. | editor-last1 = Colledge | editor-first2 = Brian R. | editor-last2 = Walker | editor-first3 = Stuart H. | editor-last3 = Ralston | name-list-style = vanc |others=Illustrated by Robert Britton|title=Davidson's principles and practice of medicine |date=2010|publisher=Churchill Livingstone/Elsevier|location=Edinburgh|isbn=978-0-7020-3085-7|edition=21st |ref={{harvid|Davidson's|2010}}}}
* {{cite book|last1=Ort|first1=Victoria|last2=Bogart|first2=Bruce Ian | name-list-style = vanc |title=Elsevier's integrated anatomy and embryology|date=2007|publisher=Elsevier Saunders|location=Philadelphia, Pa.|isbn=978-1-4160-3165-9|ref={{harvid|Elsevier's|2007}}}}
* {{cite book|editor-first1= Susan | editor-last1 = Standring | editor-first2 = Neil R. | editor-last2 = Borley | name-list-style = vanc |display-editors=etal |title=Gray's anatomy: the anatomical basis of clinical practice|date=2008|publisher=Churchill Livingstone|location=London|isbn=978-0-8089-2371-8|edition=40th|ref={{harvid|Gray's Anatomy|2008}}}}
{{refend}}

== External links ==
{{Commons category|Thyroid}}
* [https://www.endocrineweb.com/endocrinology/overview-thyroid Endocrine Web: Thyroid]
 
{{Endocrine system anatomy}}

{{Authority control}}

[[Category:Thyroid| ]]
[[Category:Glands]]
[[Category:Endocrine system anatomy]]
[[Category:Human head and neck]]