Editing Thyroid (section)

== 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|url-status=dead}}</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 | url-status = dead }}</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|pathomnomonic]] features such as involvement of the eyes and shins, or isolation of autoantibodies, or by results of a radiolabelled uptake scan. Graves' disease is treated with anti-thyroid drugs such as propylthiouracil, which decrease the production of thyroid hormones, but hold a high rate of relapse. If there is no involvement of the eyes, then use of radioactive isotopes to ablate the gland may be considered. Surgical removal of the gland with subsequent thyroid hormone replacement may be considered, however this will not control symptoms associated with the eye or skin.<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|url-status=dead|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]] [[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=http://news.bbc.co.uk/hi/english/sci/tech/newsid_1319000/1319386.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 |url-status=dead }}</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/>