The thyroid, or thyroid gland, is an

endocrine gland Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid ...

vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

. In humans it is in the

neck The neck is the part of the body on many vertebrates that connects the head with the torso. The neck supports the weight of the head and protects the nerves that carry sensory and motor information from the brain down to the rest of the body. In ...

and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below the

Adam's apple The Adam's apple or laryngeal prominence is the protrusion in the human neck formed by the angle of the thyroid cartilage surrounding the larynx, typically visible in men, less frequently in women. Structure The topographic structure which is e ...

. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing

colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others exten ...

. The thyroid gland secretes three hormones: the two

thyroid hormones File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 38 ...

triiodothyronine (T₃) and thyroxine (T₄)and a

peptide hormone Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing th ...

. The thyroid hormones influence the

metabolic rate Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

and

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...

, and in children, growth and development. Calcitonin plays a role in

calcium homeostasis Calcium metabolism is the movement and regulation of calcium ions (Ca2+) ''in'' (via the gut) and ''out'' (via the gut and kidneys) of the body, and ''between'' body compartments: the blood plasma, the extracellular and intracellular fluids, and ...

. Secretion of the two thyroid hormones is regulated by

thyroid-stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism ...

(TSH), which is secreted from the

anterior pituitary A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...

gland. TSH is regulated by

thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary. TRH has been used clinica ...

(TRH), which is produced by the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...

. The thyroid gland develops in the floor of the

pharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its str ...

at the base of the tongue at 3–4 weeks gestation; it then descends in front of the pharyngeal gut, and ultimately over the next few weeks, it migrates to the base of the neck. During migration, the thyroid remains connected to the tongue by a narrow canal, the

thyroglossal duct The thyroglossal duct is an embryological anatomical structure forming an open connection between the initial area of development of the thyroid gland and its final position. It is located exactly mid-line, between the anterior 2/3 and posterior ...

. 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. Euthyroid is the term used to describe a state of normal thyroid function in the body. Thyroid disorders include

hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...

hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...

, thyroid

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

( thyroiditis), thyroid enlargement (

goitre A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...

thyroid nodule Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic ...

s, and

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. Canc ...

. Hyperthyroidism is characterized by excessive secretion of thyroid hormones: the most common cause is the

autoimmune disorder An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

Graves' disease Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...

. Hypothyroidism is characterized by a deficient secretion of thyroid hormones: the most common cause is

iodine deficiency Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated c ...

. In iodine-deficient regions, hypothyroidism secondary to iodine deficiency is the leading cause of preventable intellectual disability in children. In iodine-sufficient regions, the most common cause of hypothyroidism is the autoimmune disorder

Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...

. The presence of the thyroid and its various diseases have been noted and treated for centuries, although the gland itself has only been described and named since the

Renaissance The Renaissance ( , ) , from , with the same meanings. is a period in European history marking the transition from the Middle Ages to modernity and covering the 15th and 16th centuries, characterized by an effort to revive and surpass ide ...

. Knowledge of the thyroid, its biochemistry, and its disorders developed throughout the late nineteenth and twentieth centuries. Many modern treatments and investigative modalities evolved throughout the mid-twentieth century, including refinement of surgical techniques for thyroid removal (

thyroidectomy A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condi ...

) for the treatment of goitre; the use of radioactive iodine and

thiouracil Thiouracil may refer to: * 2-Thiouracil * 4-Thiouracil {{Short pages monitorThe thyroid hormones also play a role in maintaining normal sexual function, sleep, and thought patterns. Increased levels are associated with increased speed of thought generation but decreased focus. Sexual function, including libido and the maintenance of a normal

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of egg ...

, are influenced by thyroid hormones. After secretion, only a very small proportion of the thyroid hormones travel freely in the blood. Most are bound to

thyroxine-binding globulin Thyroxine-binding globulin (TBG) is a globulin protein that in humans is encoded by the ''SERPINA7'' gene. TBG binds thyroid hormones in circulation. It is one of three transport proteins (along with transthyretin and serum albumin) responsib ...

(about 70%), transthyretin (10%), and

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumin ...

(15%). Only the 0.03% of T₄ and 0.3% of T₃ traveling freely have hormonal activity. In addition, up to 85% of the T₃ in blood is produced following conversion from T₄ by

iodothyronine deiodinase Iodothyronine deiodinases ( and ) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T4), the precursor of 3,5,3'-triiodothyronine (T3) is transformed into T3 by deiodinase activity ...

s in organs around the body. Thyroid hormones act by crossing the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

and binding to

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

nuclear

thyroid hormone receptor The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have ...

s TR-α₁, TR-α₂, TR-β₁, and TR-β₂, which bind with

hormone response element Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes. Under conditions of stress, a transcription activator protein binds ...

s and

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s to modulate

DNA transcription Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...

. In addition to these actions on DNA, the thyroid hormones also act within the cell membrane or within cytoplasm via reactions with

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

s, including

calcium ATPase Ca2+ ATPase is a form of P-ATPase that transfers calcium after a muscle has contracted. The two kinds of calcium ATPase are: *Plasma membrane Ca2+ ATPase (PMCA) *Sarcoplasmic reticulum Ca2+ ATPase (SERCA) Plasma membrane Ca2+ ATPase (PMCA) Pl ...

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

, and

glucose transporter Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporte ...

Hormone production

The thyroid hormones are created from

thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...

. This is a protein within the colloid in the follicular lumen that is originally created within the

rough endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

of follicular cells and then transported into the follicular lumen. Thyroglobulin contains 123 units of

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

, which reacts with iodine within the follicular lumen.

Iodine Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vio ...

is essential for the production of the thyroid hormones. Iodine (I⁰) travels in the blood as

iodide An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered as a component of iodized salt, which many governments mandate. Worldwide, iodine defi ...

(I⁻), which is taken up into the follicular cells by a

sodium-iodide symporter The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the ''SLC5A5'' gene. It is a transmembrane glycoprotein with a molecular weight of 87 k Da and 13 transmembrane domains, wh ...

. This is an

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...

on the cell membrane which in the same action transports two sodium ions and an iodide ion into the cell. Iodide then travels from within the cell into the lumen, through the action of

pendrin Pendrin is an anion exchange protein that in humans is encoded by the ''SLC26A4'' gene (solute carrier family 26, member 4). Pendrin was initially identified as a sodium-independent chloride-iodide exchanger with subsequent studies showing that i ...

, an iodide-chloride

antiporter An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma me ...

. In the follicular lumen, the iodide is then

oxidized Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

to iodine. This makes it more reactive, and the iodine is attached to the active tyrosine units in thyroglobulin by the enzyme

thyroid peroxidase Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine r ...

. This forms the precursors of thyroid hormones

monoiodotyrosine 3-Iodotyrosine is an intermediate in the synthesis of thyroid hormones which is derived from iodination of tyrosine at the meta-position of the benzene ring. One unit can combine with diiodotyrosine to form triiodothyronine, as occurs in the col ...

(MIT), and

diiodotyrosine Diiodotyrosine (DIT) is a precursor in the production of thyroid hormone, and results from iodization of monoiodotyrosine at the other meta- position on the phenol ring. Function DIT is a modulator of the enzyme thyroid peroxidase (which is invo ...

(DIT). When the follicular cells are stimulated by

, the follicular cells reabsorb thyroglobulin from the follicular lumen. The iodinated tyrosines are cleaved, forming the thyroid hormones T₄, T₃, DIT, MIT, and traces of

reverse triiodothyronine Reverse triiodothyronine (3,3′,5′-triiodothyronine, reverse T3, or rT3) is an isomer of triiodothyronine (3,5,3′ triiodothyronine, T3). Reverse T3 is the third-most common iodothyronine the thyroid gland releases into the bloodstream, at 0.9 ...

. T₃ and T₄ are released into the blood. The hormones secreted from the gland are about 80–90% T₄ and about 10–20% T₃.How Your Thyroid Works: A Delicate Feedback Mechanism
Updated 2009-05-21.The thyroid gland
in ''Endocrinology: An Integrated Approach'' by Stephen Nussey and Saffron Whitehead (2001) Published by BIOS Scientific Publishers Ltd. Deiodinase enzymes in peripheral tissues remove the iodine from MIT and DIT and convert T₄ to T₃ and RT_3. This is a major source of both RT₃ (95%) and T₃ (87%) in peripheral tissues.

Regulation

The production of thyroxine and triiodothyronine is primarily regulated by thyroid-stimulating hormone (TSH), released by the

gland. TSH release in turn is stimulated by

thyrotropin releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary. TRH has been used clinicall ...

(TRH), released in a pulsatile manner from the

. The thyroid hormones provide

negative feedback Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...

to the thyrotropes TSH and TRH: when the thyroid hormones are high, TSH production is suppressed. This negative feedback also occurs when levels of TSH are high, causing TRH production to be suppressed. TRH is secreted at an increased rate in situations such as cold exposure in order to stimulate thermogenesis. In addition to being suppressed by the presence of thyroid hormones, TSH production is blunted by

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% ...

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coup ...

, and

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

Calcitonin

The thyroid gland also produces the hormone

, which helps regulate blood

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...

levels. Parafollicular cells produce calcitonin in response to

high blood calcium Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalce ...

. Calcitonin decreases the release of calcium from bone, by decreasing the activity of

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pr ...

s, cells which break down bone. Bone is constantly reabsorbed by osteoclasts and created by

osteoblast Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts functio ...

s, so calcitonin effectively stimulates movement of calcium into

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, an ...

. The effects of calcitonin are opposite those of the

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. PTH influences bone r ...

(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 (

), but not the

parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes pa ...

Gene and protein expression

About 20,000 protein coding genes are expressed in human cells: 70% of these genes are expressed in thyroid cells. Two-hundred 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—

, TPO, and IYD; while in the parafollicular c-cells, they direct calcitonin synthesis—

CALCA Calca may refer to: * Calca Peninsula, a peninsula in South Australia * Calca Province, one of thirteen provinces in the Cusco Region of Peru * Calca District, one of the eight districts in the Calca Province * Calca, Peru, capital of the Calca Dis ...

, and

CALCB Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produc ...

Clinical significance

General practitioners, and internal medicine specialists play a role in identifying and monitoring the treatment of thyroid disease. Endocrinologists and

thyroidologist A thyroidologist is a medical practitioner specializing in the thyroid and related areas. In the United States it refers to a board certified endocrinologist physician, who is either a full time academician with multiple responsibilities beside t ...

s are thyroid specialists. Thyroid surgeons or otolaryngologists are responsible for the surgical management of thyroid disease.

Functional disorders

Hyperthyroidism

Excessive production of the thyroid hormones is called

. Causes include

, toxic multinodular goitre, solitary

thyroid adenoma A thyroid adenoma is a benign tumor of the thyroid gland, that may be inactive or active (functioning autonomously) as a toxic adenoma. Signs and symptoms A thyroid adenoma may be clinically silent ("cold" adenoma), or it may be a functional tumor ...

, inflammation, and a

pituitary adenoma Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibri ...

, or following iodinated contrast

imaging Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image). Imaging technology is the application of materials and methods to create, preserve, or duplicate images. ...

. Hyperthyroidism often causes a variety of

non-specific symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

including weight loss, increased appetite, insomnia, decreased tolerance of heat, tremor,

palpitations Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...

, anxiety and nervousness. In some cases it can cause

chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

, hair loss and muscle weakness. Such symptoms may be managed temporarily with drugs such as

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...

s. Long-term management of hyperthyroidism may include drugs that suppress thyroid function such as

propylthiouracil Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is t ...

carbimazole Carbimazole (brand names Neo-Mercazole, Anti-Thyrox, etc.) is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodina ...

and methimazole. Alternatively, 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 A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...

will depend on the individual and on the country where being treated. Surgery to remove the thyroid can sometimes be performed as a transoral thyroidectomy, a

minimally invasive procedure Minimally invasive procedures (also known as minimally invasive surgeries) encompass surgical techniques that limit the size of incisions needed, thereby reducing wound healing time, associated pain, and risk of infection. Surgery by definition ...

. Surgery does however carry a risk of damage to the

s and the

recurrent laryngeal nerve The recurrent laryngeal nerve (RLN) is a branch of the vagus nerve (cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recurrent laryngeal nerves, right and l ...

, which innervates the

vocal cords In humans, vocal cords, also known as vocal folds or voice reeds, are folds of throat tissues that are key in creating sounds through vocalization. The size of vocal cords affects the pitch of voice. Open when breathing and vibrating for speech ...

. If the entire thyroid gland is removed, hypothyroidism will inevitably result, and thyroid hormone substitutes will be needed.

Hypothyroidism

An underactive thyroid gland results in

. Typical symptoms are abnormal weight gain, tiredness,

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

heavy menstrual bleeding Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB). Abnormal uterine bleeding can be caused by structural abnorm ...

, hair loss, cold intolerance, and a slow heart rate.

Iodine deficiency Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated c ...

is the most common cause of hypothyroidism worldwide, and the autoimmune disease

is the most common cause in the developed world. Other causes include congenital abnormalities, diseases causing transient inflammation, surgical removal or radioablation of the thyroid, the drugs

amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibri ...

and

lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid e ...

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weigh ...

, and

sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly a ...

. Some forms of hypothyroidism can result in

myxedema Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hyperthyroidism and (rare) paradoxical cases of hypothyroidism. In this latter sense, myxedem ...

and severe cases can result in myxedema coma. Hypothyroidism is managed with replacement of the

. This is usually given daily as an oral supplement, and may take a few weeks to become effective. Some causes of hypothyroidism, such as

Postpartum thyroiditis Postpartum thyroiditis refers to thyroid dysfunction occurring in the first 12 months after pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. According to the National Institute of Health, postpartum thyroiditi ...

and

Subacute thyroiditis Subacute thyroiditis is a form of thyroiditis that can be a cause of both thyrotoxicosis and hypothyroidism. It is uncommon and can affect individuals of both sexes, occurring three times as often in women than in men. and people of all ages. The m ...

may be transient and pass over time, and other causes such as iodine deficiency may be able to be rectified with dietary supplementation.

Diseases

Graves' disease

is an autoimmune disorder that is the most common cause of hyperthyroidism. In Graves' disease, for an unknown reason

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

develop against the thyroid stimulating hormone receptor. These antibodies activate the receptor, leading to development of a goitre and symptoms of hyperthyroidism, such as heat intolerance, weight loss, diarrhoea and palpitations. Occasionally such antibodies block but do not activate the receptor, leading to symptoms associated with hypothyroidism. In addition, gradual protrusion of the eyes may occur, called Graves' ophthalmopathy, as may swelling of the front of the shins. Graves' disease can be diagnosed by the presence of pathomnomonic features such as involvement of the eyes and shins, or isolation of autoantibodies, or by results of a radiolabelled uptake scan. Graves' disease is treated with anti-thyroid drugs such as propylthiouracil, which decrease the production of thyroid hormones, but hold a high rate of relapse. If there is no involvement of the eyes, then use of radioactive isotopes to ablate the gland may be considered. Surgical removal of the gland with subsequent thyroid hormone replacement may be considered, however this will not control symptoms associated with the eye or skin.

Nodules

Thyroid nodule Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic ...

s are often found on the gland, with a

prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

of 4–7%. The majority of nodules do not cause any symptoms, thyroid hormone secretion is normal, and they are non-cancerous. Non-cancerous cases include simple

cyst A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...

colloid nodule Colloid nodules, also known as adenomatous nodules or colloid nodular goiter are benign, noncancerous enlargement of thyroid tissue. Although they may grow large, and there may be more than one, they are not malignant and they will not spread beyon ...

s, and

s. Malignant nodules, which only occur in about 5% of nodules, include follicular, papillary, medullary carcinomas and

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...

from other sites Nodules are more likely in females, those who are exposed to radiation, and in those who are iodine deficient. When a nodule is present, thyroid function tests determine whether the nodule is secreting excess thyroid hormones, causing hyperthyroidism. When the thyroid function tests are normal, an

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

is often used to investigate the nodule, and provide information such as whether the nodule is fluid-filled or a solid mass, and whether the appearance is suggestive of a benign or malignant cancer. A

needle aspiration biopsy Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, aft ...

may then be performed, and the sample undergoes cytology, in which the appearance of cells is viewed to determine whether they resemble normal or cancerous cells. The presence of multiple nodules is called a

multinodular goitre A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...

; and if it is associated with hyperthyroidism, it is called a toxic multinodular goitre.

Goitre

An enlarged thyroid gland is called a

. Goitres are present in some form in about 5% of people, and are the result of a large number of causes, including iodine deficiency,

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

(both Graves' disease and Hashimoto's thyroiditis), infection, inflammation, and infiltrative disease such as

and

. Sometimes no cause can be found, a state called "simple goitre". Some forms of goitre are associated with pain, whereas many do not cause any symptoms. Enlarged goitres may extend beyond the normal position of the thyroid gland to below the sternum, around the airway or esophagus. Goitres may be associated with hyperthyroidism or hypothyroidism, relating to the underlying cause of the goitre. Thyroid function tests may be done to investigate the cause and effects of the goitre. The underlying cause of the goitre may be treated, however many goitres with no associated symptoms are simply monitored.

Inflammation

Inflammation of the thyroid is called thyroiditis, and may cause symptoms of hyperthyroidism or hypothyroidism. Two types of thyroiditis initially present with hyperthyroidism and are sometimes followed by a period of hypothyroidism – Hashimoto's thyroiditis and

postpartum thyroiditis Postpartum thyroiditis refers to thyroid dysfunction occurring in the first 12 months after pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. According to the National Institute of Health, postpartum thyroiditi ...

. There are other disorders that cause inflammation of the thyroid, and these include

subacute thyroiditis Subacute thyroiditis is a form of thyroiditis that can be a cause of both thyrotoxicosis and hypothyroidism. It is uncommon and can affect individuals of both sexes, occurring three times as often in women than in men. and people of all ages. The m ...

, acute thyroiditis, silent thyroiditis, Riedel's thyroiditis and traumatic injury, including

palpation thyroiditis Palpation thyroiditis refers to the development of thyroid inflammation due to mechanical damage to thyroid follicles. This can occur by vigorous repeated palpation (as with thyroid examination) or surgical manipulation (as can occur with radical ...

is an

in which the thyroid gland is infiltrated by the

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

and

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

s. These progressively destroy the thyroid gland. In this way, Hasimoto's thyroiditis may have occurred insidiously, and only be noticed when thyroid hormone production decreases, causing symptoms of hypothyroidism. Hashimoto's is more common in females than males, much more common after the age of 60, and has known genetic risk factors. Also more common in individuals with Hashimoto's thyroiditis are

Type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar fo ...

pernicious anaemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...

Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...

vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

occurs in some females following

childbirth Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births global ...

. After delivery, the gland becomes inflamed and the condition initially presents with a period of hyperthyroidism followed by hypothyroidism and, usually, a return to normal function. The course of the illness takes place over several months, and is characterised by a painless goitre. Antibodies against thyroid peroxidase can be found on testing. The inflammation usually resolves without treatment, although thyroid hormone replacement may be needed during the period of hypothyroidism.

Cancer

The most common

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

affecting the thyroid gland is a benign

adenoma An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adeno ...

, usually presenting as a painless mass in the neck. Malignant thyroid cancers are most often

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...

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. Radiation of the head and neck presents a

risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often ...

for thyroid cancer, and cancer is more common in women than men, occurring at a rate of about 2:1. In most cases, thyroid cancer presents as a painless mass in the neck. It is very unusual for thyroid cancers to present with other symptoms, although in some cases cancer may cause hyperthyroidism. Most malignant thyroid cancers are papillary, followed by follicular, medullary, and thyroid lymphoma. Because of the prominence of the thyroid gland, cancer is often detected earlier in the course of disease as the cause of a nodule, which may undergo fine-needle aspiration. Thyroid function tests will help reveal whether the nodule produces excess thyroid hormones. A radioactive iodine uptake test can help reveal the activity and location of the cancer and metastases. Thyroid cancers are treated by removing the whole or part of thyroid gland. Radioactive

Iodine-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuc ...

may be given to radioablate the thyroid.

Thyroxine File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

is given to replace the hormones lost and to suppress TSH production, as TSH may stimulate recurrence. With the exception of the rare anaplastic thyroid cancer, which carries a very poor prognosis, most thyroid cancers carry an excellent prognosis and can even be considered curable.

Congenital

A persistent thyroglossal duct is the most common clinically significant

birth defect A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

of the thyroid gland. A persistent sinus tract may remain as a vestigial remnant of the tubular development of the thyroid gland. Parts of this tube may be obliterated, leaving small segments to form thyroglossal cysts. Preterm neonates are at risk of hypothyroidism as their thyroid glands are insufficiently developed to meet their postnatal needs. In order to detect hypothyroidism in newborn babies, to prevent growth and development abnormalities in later life, many countries have

newborn screening Newborn screening (NBS) is a public health program of screening in infants shortly after birth for conditions that are treatable, but not clinically evident in the newborn period. The goal is to identify infants at risk for these conditions ear ...

programs at birth. Infants with thyroid hormone deficiency ( congenital hypothyroidism) can manifest problems of physical growth and development as well as brain development, termed

cretinism Congenital iodine deficiency syndrome is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It ...

. Children with congenital hypothyroidism are treated supplementally with

levothyroxine Levothyroxine, also known as -thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to t ...

, which facilitates normal growth and development. Mucinous, clear secretions may collect within these cysts to form either spherical masses or fusiform swellings, rarely larger than 2 to 3 cm in diameter. These are present in the midline of the

anterior to the

trachea The trachea, also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends from the l ...

. Segments of the duct and cysts that occur high in the neck are lined by

stratified squamous epithelium A stratified squamous epithelium consists of squamous (flattened) epithelial cells arranged in layers upon a basal membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural i ...

, which is essentially identical to that covering the posterior portion of the

tongue The tongue is a muscular organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive process, and is the primary organ of taste. The tongue's upper surface (dorsum) is covered by taste b ...

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. Superimposed infection may convert these lesions into abscess cavities, and rarely, give rise to cancers. Another disorder is that of

thyroid dysgenesis Thyroid dysgenesis is a cause of congenital hypothyroidism where the thyroid is missing, ectopic, or severely underdeveloped. It should not be confused with iodine deficiency, or with other forms of congenital hypothyroidism, such as thyroid dysh ...

which can result in various presentations of one or more misplaced accessory thyroid glands. These can be asymptomatic.

Iodine

The thyroid gland in health and disease (1917) (14780980651)

, most common in inland and mountainous areas, can predispose to goitre – if widespread, known as endemic goitre. Pregnant women deficient of iodine can give birth to infants with thyroid hormone deficiency. The use of

iodised salt Iodised salt (American and British English spelling differences#-ise, -ize (-isation, -ization), also spelled iodized salt) is table salt mixed with a minute amount of various salts of the element iodine. The ingestion of iodine prevents iodine ...

to add iodine to the diet has eliminated endemic cretinism in most developed countries, and over 120 countries have made the iodination of

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantiti ...

mandatory. Because the thyroid concentrates iodine, it also concentrates the various radioactive

isotope Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numbers ...

s of iodine produced by

nuclear fission Nuclear fission is a reaction in which the nucleus of an atom splits into two or more smaller nuclei. The fission process often produces gamma photons, and releases a very large amount of energy even by the energetic standards of r ...

. In the event of large accidental releases of such material into the environment, the uptake of radioactive iodine isotopes by the thyroid can, in theory, be blocked by saturating the uptake mechanism with a large surplus of non-radioactive iodine, taken in the form of potassium iodide tablets. One consequence of the

Chernobyl disaster The Chernobyl disaster was a nuclear accident that occurred on 26 April 1986 at the No. 4 reactor in the Chernobyl Nuclear Power Plant, near the city of Pripyat in the north of the Ukrainian SSR in the Soviet Union. It is one of only two nuc ...

was an increase in

s in children in the years following the accident. Excessive iodine intake is uncommon and usually has no effect on the thyroid function. Sometimes though it may cause hyperthyroidism, and sometimes hypothyroidism with a resulting goitre.

Evaluation

The thyroid is examined by observation of the gland and surrounding neck for swelling or enlargement. It is then

felt Felt is a textile material that is produced by matting, condensing and pressing fibers together. Felt can be made of natural fibers such as wool or animal fur, or from synthetic fibers such as petroleum-based acrylic or acrylonitrile or wood ...

, usually from behind, and a person is often asked to swallow to better feel the gland against the fingers of the examiner. The gland moves up and down with swallowing because of its attachments to the thyroid and cricoid cartilages. In a healthy person the gland is not visible yet is

palpable Palpation is the process of using one's hands to check the body, especially while perceiving/diagnosing a disease or illness. Usually performed by a health care practitioner, it is the process of feeling an object in or on the body to determin ...

as a soft mass. Examination of the thyroid gland includes the search for abnormal masses and the assessment of overall thyroid size. The character of the thyroid, swellings, nodules, and their consistency may all be able to be felt. If a goitre is present, an examiner may also feel down the neck consider

tapping Tapping is a playing technique that can be used on any stringed instrument, but which is most commonly used on guitar. The technique involves a string being fretted and set into vibration as part of a single motion. This is in contrast to stand ...

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 The stethoscope is a medical device for auscultation, or listening to internal sounds of an animal or human body. It typically has a small disc-shaped resonator that is placed against the skin, and one or two tubes connected to two earpieces. ...

for

bruit Bruit, also called vascular murmur, is the abnormal sound generated by turbulent flow of blood in an artery due to either an area of partial obstruction or a localized high rate of blood flow through an unobstructed artery. The bruit may be hear ...

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.

Tests

Thyroid function tests include a battery of

blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholest ...

s, including the measurement of the thyroid hormones, as well as the measurement of thyroid stimulating hormone (TSH). They may reveal hyperthyroidism (high T₃ and T₄), hypothyroidism (low T₃, T₄), or subclinical hyperthyroidism (normal T₃ and T₄ with a low TSH). TSH levels are considered the most sensitive marker of thyroid dysfunction. They are however not always accurate, particularly if the cause of hypothyroidism is thought to be related to insufficient

(TRH) secretion, in which case it may be low or falsely normal. In such a case a TRH stimulation test, in which TRH is given and TSH levels are measured at 30 and 60-minutes after, may be conducted. T₃ and T₄ can be measured directly. However, as the two thyroid hormones travel bound to other molecules, and it is the "free" component that is biologically active, free T₃ and free T₄ levels can be measured. T₃ is preferred, because in hypothyroidism T₃ levels may be normal. The ratio of bound to unbound thyroid hormones is known as the thyroid hormone binding ratio (THBR). It is also possible to measure directly the main carriers of the thyroid hormones, thryoglobulin and throxine-binding globulin. Thyroglobulin will also be measurable in a healthy thyroid, and will increase with inflammation, and may also be used to measure the success of thyroid removal or ablation. If successful, thyroglobulin should be undetectable. Lastly, antibodies against components of the thyroid, particularly anti-TPO and anti-thyroglobulin, can be measured. These may be present in normal individuals but are highly sensitive for autoimmune-related disease.

Imaging

Ultrasound of the thyroid may be used to reveal whether structures are solid or filled with fluid, helping to differentiate between nodules and goitres and cysts. It may also help differentiate between malignant and benign lesions. When further imaging is required, a radiolabelled

iodine-123 Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2230 hours; the decay by electron capture to tellu ...

technetium-99 Technetium-99 (99Tc) is an isotope of technetium which decays with a half-life of 211,000 years to stable ruthenium-99, emitting beta particles, but no gamma rays. It is the most significant long-lived fission product of uranium fission, producin ...

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 outside the thyroid. A

fine needle aspiration Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, af ...

of a sample of thyroid tissue may be taken in order to evaluate a lesion seen on ultrasound which is then sent for

histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...

and cytology. Computed tomography of the thyroid plays an important role in the evaluation of thyroid cancer.Creative Commons Attribution 4.0 International License
/ref> CT scans often incidentally find thyroid abnormalities, and thereby practically becomes the first investigation modality.

History

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

Antiquity

The presence and diseases of the thyroid have been noted and treated for thousands of years. In 1600 BCE burnt

sponge Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through ...

and

seaweed Seaweed, or macroalgae, refers to thousands of species of macroscopic, multicellular, marine algae. The term includes some types of ''Rhodophyta'' (red), '' Phaeophyta'' (brown) and ''Chlorophyta'' (green) macroalgae. Seaweed species such a ...

(which contain iodine) were used within China for the treatment of goitres, a practice which has developed in many parts of the world. In

Ayurvedic medicine Ayurveda () is an alternative medicine system with historical roots in the Indian subcontinent. The theory and practice of Ayurveda is pseudoscientific. Ayurveda is heavily practiced in India and Nepal, where around 80% of the population repor ...

, the book

Sushruta Samhita The ''Sushruta Samhita'' (सुश्रुतसंहिता, IAST: ''Suśrutasaṃhitā'', literally "Suśruta's Compendium") is an ancient Sanskrit text on medicine and surgery, and one of the most important such treatises on this subje ...

written about 1400 BCE described hyperthyroidism, hypothyroidism and goitre.

Aristotle Aristotle (; grc-gre, Ἀριστοτέλης ''Aristotélēs'', ; 384–322 BC) was a Greek philosopher and polymath during the Classical period in Ancient Greece. Taught by Plato, he was the founder of the Peripatetic school of ...

and

Xenophon Xenophon of Athens (; grc, Ξενοφῶν ; – probably 355 or 354 BC) was a Greek military leader, philosopher, and historian, born in Athens. At the age of 30, Xenophon was elected commander of one of the biggest Greek mercenary armies of ...

in the fifth century BCE describe cases of diffuse toxic goitre. Hippocrates and Plato in the fourth century BCE provided some of the first descriptions of the gland itself, proposing its function as a salivary gland.

Pliny the Elder Gaius Plinius Secundus (AD 23/2479), called Pliny the Elder (), was a Roman author, naturalist and natural philosopher, and naval and army commander of the early Roman Empire, and a friend of the emperor Vespasian. He wrote the encyclopedic ...

in the first century BCE referred to epidemics of goitre in the

Alps The Alps () ; german: Alpen ; it, Alpi ; rm, Alps ; sl, Alpe . are the highest and most extensive mountain range system that lies entirely in Europe, stretching approximately across seven Alpine countries (from west to east): France, Swi ...

and proposed treatment with burnt seaweed, a practice also referred to by

Galen Aelius Galenus or Claudius Galenus ( el, Κλαύδιος Γαληνός; September 129 – c. AD 216), often Anglicized as Galen () or Galen of Pergamon, was a Greek physician, surgeon and philosopher in the Roman Empire. Considered to be one o ...

in the second century, referred to burnt sponge for the treatment of goitre. The

Chinese Chinese can refer to: * Something related to China * Chinese people, people of Chinese nationality, citizenship, and/or ethnicity **''Zhonghua minzu'', the supra-ethnic concept of the Chinese nation ** List of ethnic groups in China, people of v ...

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

text '' Shennong Ben Cao Jing'', written ca. 200–250, also refers to goitre.

Scientific era

In 1500 polymath Leonardo da Vinci provided the first illustration of the thyroid. In 1543 anatomist

Andreas Vesalius Andreas Vesalius (Latinized from Andries van Wezel) () was a 16th-century anatomist, physician, and author of one of the most influential books on human anatomy, '' De Humani Corporis Fabrica Libri Septem'' (''On the fabric of the human body'' ...

gave the first anatomic description and illustration of the gland. In 1656 the thyroid received its modern name, by the anatomist Thomas Wharton. The gland was named thyroid, meaning shield, as its shape resembled the shields commonly used in Ancient Greece. The English name ''thyroid gland'' is derived from the medical Latin used by Wharton – . means 'gland' in Latin, and can be traced back to the Ancient Greek word , meaning 'shield-like/shield-shaped'. French chemist Bernard Courtois discovered iodine in 1811, and in 1896

Eugen Baumann Eugen Baumann (12 December 1846 – 3 November 1896) was a German chemist. He was one of the first people to create polyvinyl chloride (PVC), and, together with Carl Schotten, he discovered the Schotten-Baumann reaction. Life Baumann was born i ...

documented it as the central ingredient in the thyroid gland. He did this by boiling the thyroid glands of a thousand sheep, and named the precipitate, a combination of the thyroid hormones, 'iodothyrin'. David Marine in 1907 proved that iodine is necessary for thyroid function. Graves' disease was described by Robert James Graves in 1834. The role of the thyroid gland in metabolism was demonstrated in 1895 by Adolf Magnus-Levy. Thyroxine was first isolated in 1914 and synthesized in 1927, and triiodothyroxine in 1952. The conversion of T₄ to T₃ was discovered in 1970. The process of discovering TSH took place over the early to mid twentieth century. TRH was discovered by Polish endocrinologist Andrew Schally in 1970, contributing in part to his Nobel Prize in Medicine in 1977. In the nineteenth century numerous authors described both

and

, and their relationship to the thyroid. Charles Mayo coined the term hyperthyroidism in 1910. Hakaru Hashimoto documented a case of Hashimoto's thyroiditis in 1912,

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

in this disease were demonstrated in 1956. Knowledge of the thyroid and its conditions developed throughout the late nineteenth and twentieth centuries, with many modern treatments and investigative modalities evolving throughout the mid twentieth century, including the use of radioactive iodine, thiouracil and fine needle aspiration.

Surgery

Either Aetius in the sixth century CE or Persian Ali ibn Abbas al-Magusi in 990 CE conducted the first recorded thyroidectomy as a treatment for goitre. Operations remained risky and generally were not successful until the 19th century, when descriptions emerged from a number of authors including Prussian surgeon

Theodor Billroth Christian Albert Theodor Billroth (26 April 18296 February 1894) was a German surgeon and amateur musician. As a surgeon, he is generally regarded as the founding father of modern abdominal surgery. As a musician, he was a close friend and con ...

, Swiss surgeon and physiologist Theodor Kocher, American physician Charles Mayo, American surgeons William Halsted and George Crile. These descriptions provided the basis for modern thyroid surgery. Theodor Kocher went on to win the

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute, Nobel Assembly at the Karolinska Institutet, Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Pr ...

in 1909 "for his work on the physiology, pathology and surgery of the thyroid gland".

Other animals

The thyroid gland is found in all

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, wi ...

s. In fish, it is usually located below the gills and is not always divided into distinct lobes. However, in some

teleost Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tel ...

s, patches of thyroid tissue are found elsewhere in the body, associated with the kidneys, spleen, heart, or eyes. In

tetrapod Tetrapods (; ) are four-limbed vertebrate animals constituting the superclass Tetrapoda (). It includes extant and extinct amphibians, sauropsids (reptiles, including dinosaurs and therefore birds) and synapsids (pelycosaurs, extinct therapsid ...

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 Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fu ...

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

lamprey Lampreys (sometimes inaccurately called lamprey eels) are an ancient extant lineage of jawless fish of the order Petromyzontiformes , placed in the superclass Cyclostomata. The adult lamprey may be characterized by a toothed, funnel-like ...

s, the thyroid originates as an

exocrine gland Exocrine glands are glands that secrete substances on to an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of tw ...

, 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 A tunicate is a marine invertebrate animal, a member of the subphylum Tunicata (). It is part of the Chordata, a phylum which includes all animals with dorsal nerve cords and notochords (including vertebrates). The subphylum was at one time ...

s and amphioxi (lancelets), have a structure very similar to that of larval lampreys (the

endostyle The endostyle is an anatomical feature found in invertebrate chordates and larval lampreys. It is an organ which assists chordates in filter-feeding. It is found in adult urochordates and cephalochordates, as well as in the larvae of the verte ...

), and this also secretes iodine-containing compounds, though not thyroxine. Thyroxine is critical to

metabolic regulation Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

, and growth throughout the vertebrate clade. Iodine and T₄ trigger the

change Change or Changing may refer to: Alteration * Impermanence, a difference in a state of affairs at different points in time * Menopause, also referred to as "the change", the permanent cessation of the menstrual period * Metamorphosis, or change, ...

from a plant-eating water-dwelling

tadpole A tadpole is the larval stage in the biological life cycle of an amphibian. Most tadpoles are fully aquatic, though some species of amphibians have tadpoles that are terrestrial. Tadpoles have some fish-like features that may not be found i ...

into a meat-eating land-dwelling

frog A frog is any member of a diverse and largely carnivorous group of short-bodied, tailless amphibians composing the order Anura (ανοὐρά, literally ''without tail'' in Ancient Greek). The oldest fossil "proto-frog" ''Triadobatrachus'' is ...

, 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, don't transform into land-dwelling adults, and live and reproduce in the larval form of aquatic

axolotl The axolotl (; from nci, āxōlōtl ), ''Ambystoma mexicanum'', is a paedomorphic salamander closely related to the tiger salamander. Axolotls are unusual among amphibians in that they reach adulthood without undergoing metamorphosis. Instea ...

. Among

amphibian Amphibians are four-limbed and ectothermic vertebrates of the class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terrestrial, fossorial, arbor ...

s, administering a thyroid-blocking agent such as

(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 Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes inclu ...

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 Evolution is change in the heredity, heritable Phenotypic trait, characteristics of biological populations over successive generations. These characteristics are the Gene expression, expressions of genes, which are passed on from parent to ...

of the human brain.

References

Books

* * * * * * *

External links

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

Hormone production

Regulation

Calcitonin

Gene and protein expression

Clinical significance

Functional disorders

Hyperthyroidism

Hypothyroidism

Diseases

Graves' disease

Nodules

Goitre

Inflammation

Cancer

Congenital

Iodine

Evaluation

Tests

Imaging

History

Antiquity

Scientific era

Surgery

Other animals

See also

References

Books

External links