Thyroid

:''Not to be confused with the parathyroid glands In vertebrate anatomy, the thyroid gland or simply, the thyroid (), is one of the largest endocrine glands. The thyroid gland is found in the neck, below (inferior to) the thyroid cartilage (which forms the laryngeal prominence, or 'Adam's Apple') and at approximately the same level as the cricoid cartilage.

The thyroid gland controls how quickly the body uses energy, makes proteins, and controls how sensitive the body should be to other hormones. It participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine (T₃) and thyroxine (T₄). These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. T₃ and T₄ are synthesized from both iodine and tyrosine. The thyroid also produces calcitonin, which plays a role in calcium homeostasis.

Hormonal output from the thyroid is regulated by thyroid-stimulating hormone (TSH) produced by the anterior pituitary, which itself is regulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus.

The thyroid gets its name from the Greek word for "shield", after the shape of the related thyroid cartilage. The most common problems of the thyroid gland consist of an overactive thyroid gland, referred to as hyperthyroidism, and an underactive thyroid gland, referred to as hypothyroidism.

Anatomy

The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or wings, lobus dexter (right lobe) and lobus sinister (left lobe), connected via the isthmus. The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath. It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence, or 'Adam's Apple'), and extends inferiorly to approximately the fifth or sixth tracheal ring. It is difficult to demarcate the gland's upper and lower border with vertebral levels because it moves position in relation to these during swallowing.

The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroidea, composed of an internal and external layer. The external layer is anteriorly continuous with the lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous with the carotid sheath. The gland is covered anteriorly with infrahyoid muscles and laterally with the sternocleidomastoid muscle also known as sternomastoid muscle. On the posterior side, the gland is fixed to the cricoid and tracheal cartilage and cricopharyngeus muscle by a thickening of the fascia to form the posterior suspensory ligament of Berry. The thyroid gland's firm attachment to the underlying trachea is the reason behind its movement with swallowing. In variable extent, Lalouette's Pyramid, a pyramidal extension of the thyroid lobe, is present at the most anterior side of the lobe. In this region, the recurrent laryngeal nerve and the inferior thyroid artery pass next to or in the ligament and tubercle.

Between the two layers of the capsule and on the posterior side of the lobes, there are on each side two parathyroid glands.

The thyroid isthmus is variable in presence and size, and can encompass a cranially extending pyramid lobe (lobus pyramidalis or processus pyramidalis), remnant of the thyroglossal duct. The thyroid is one of the larger endocrine glands, weighing 2-3 grams in neonates and 18-60 grams in adults, and is increased in pregnancy.

The thyroid is supplied with arterial blood from the superior thyroid artery, a branch of the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, and sometimes by the thyroid ima artery, branching directly from the brachiocephalic trunk. The venous blood is drained via superior thyroid veins, draining in the internal jugular vein, and via inferior thyroid veins, draining via the plexus thyroideus impar in the left brachiocephalic vein.

Lymphatic drainage passes frequently the lateral deep cervical lymph nodes and the pre- and parathracheal lymph nodes. The gland is supplied by parasympathetic nerve input from the superior laryngeal nerve and the recurrent laryngeal nerve.

Evolution

Thyroid cells phylogenetically derived from primitive iodide-concentrating gastroenteric cells (endostyle) which, during evolution, migrated and specialized in uptake and storage of iodine in follicular cellular structures, also in order to adapt the organisms from iodine-rich sea to iodine-deficient land. Venturi et al. suggested that iodide has an ancestral antioxidant function in all iodide-concentrating cells from primitive algae to more recent vertebrates. In 2008, this ancestral antioxidant action of iodides has been experimentally confirmed by Küpper et al. Since 700 million years ago thyroxine is present in fibrous exoskeletal scleroproteins of the lowest invertebrates (Porifera and Anthozoa), without showing any hormonal action. When some primitive marine chordates started to emerge from the iodine-rich sea and transferred to iodine-deficient fresh water and finally land, their diet became iodine deficient. Therefore, during progressive slow adaptation to terrestrial life, the primitive vertebrates learned to use the primitive thyroxine in order to transport antioxidant iodide into the cells. Therefore, the remaining triiodothyronine (T₃), the real active hormone, became active in the metamorphosis and thermogenesis for a better adaptation of the organisms to terrestrial environment (fresh water, atmosphere, gravity, temperature and diet). In fact, the U.S. Food and Nutrition Board and Institute of Medicine recommended daily allowance of iodine ranges from 150 micrograms /day for adult humans to 290 micrograms /day for lactating mothers. However, the thyroid gland needs no more than 70 micrograms /day to synthesize the requisite daily amounts of T₄ and T₃. These higher recommended daily allowance levels of iodine seem necessary for optimal function of a number of body systems, including lactating breast, gastric mucosa, salivary glands, oral mucosa, thymus, epidermis, choroid plexus and brain, etc.

Embryological development

In the fetus, at 3–4 weeks of gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue between the tuberculum impar and the copula linguae at a point later indicated by the foramen cecum. The thyroid then descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct. Over the next few weeks, it migrates to the base of the neck. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct.

Thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) start being secreted from the fetal hypothalamus and pituitary at 18-20 weeks of gestation, and fetal production of thyroxine (T₄) reach a clinically significant level at 18–20 weeks. Fetal triiodothyronine (T₃) remains low (less than 15 ng/dL) until 30 weeks of gestation, and increases to 50 ng/dL at term. However, preterm births can suffer neurodevelopmental disorders due to lack of maternal thyroid hormones due their own thyroid being insufficiently developed to meet their postnatal needs.

The portion of the thyroid containing the parafollicular C cells, those responsible for the production of calcitonin, are derived from the neural crest. This is first seen as the ultimobranchial body, which joins the primordial thyroid gland during its descent to its final location in the anterior neck.

Aberrations in embryological development can cause various forms of thyroid dysgenesis.

Histology

At the microscopic level, there are three primary features of the thyroid:

Disorders

Thyroid disorders include hyperthyroidism (abnormally increased activity), hypothyroidism (abnormally decreased activity) and thyroid nodules, which are generally benign thyroid neoplasms, but may be thyroid cancers. All these disorders may give rise to goiter, that is, an enlarged thyroid.

Hyperthyroidism

Hyperthyroidism, or overactive thyroid, is the overproduction of the thyroid hormones T₃ and T₄, and is most commonly caused by the development of Graves' disease, an autoimmune disease in which antibodies are produced which stimulate the thyroid to secrete excessive quantities of thyroid hormones. The disease can result in the formation of a toxic goiter as a result of thyroid growth in response to a lack of negative feedback mechanisms. It presents with symptoms such as a thyroid goiter, protruding eyes (exopthalmos), palpitations, excess sweating, diarrhea, weight loss, muscle weakness and unusual sensitivity to heat.

Beta blockers are used to decrease symptoms of hyperthyroidism such as increased heart rate, tremors, anxiety and heart palpitations, and anti-thyroid drugs are used to decrease the production of thyroid hormones, in particular, in the case of Graves' disease. These medications take several months to take full effect and have side-effects such as skin rash or a drop in white blood cell count, which decreases the ability of the body to fight off infections. These drugs involve frequent dosing (often one pill every 8 hours) and often require frequent doctor visits and blood tests to monitor the treatment, and may sometimes lose effectiveness over time. Due to the side-effects and inconvenience of such drug regimens, some patients choose to undergo radioactive iodine-131 treatment. Radioactive iodine is administered in order to destroy a proportion of or the entire thyroid gland, since the radioactive iodine is selectively taken up by the gland and gradually destroys the cells of the gland. Alternatively, the gland may be partially or entirely removed surgically, though iodine treatment is usually preferred since the surgery is invasive and carries a risk of damage to the parathyroid glands or the nerves controlling the vocal cords. If the entire thyroid gland is removed, hypothyroidism results.

Hypothyroidism

Hypothyroidism is the underproduction of the thyroid hormones T₃ and T₄. Hypothyroid disorders may occur as a result of congenital thyroid abnormalities (see congenital hypothyroidism), autoimmune disorders such as Hashimoto's thyroiditis, iodine deficiency (more likely in poorer countries) or the removal of the thyroid following surgery to treat severe hyperthyroidism and/or thyroid cancer. Typical symptoms are abnormal weight gain, tiredness, baldness, cold intolerance, and bradycardia. Hypothyroidism is treated with hormone replacement therapy, such as levothyroxine, which is typically required for the rest of the patient's life. Thyroid hormone treatment is given under the care of a physician and may take a few weeks to become effective.

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

Initial hyperthyroidism followed by hypothyroidism

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

Hashimoto's thyroiditis or Hashimoto's Disease is an autoimmune disorder whereby the body's own immune system reacts with the thyroid tissues in an attempt to destroy it. At the beginning, the gland may be overactive, and then becomes underactive as the gland is damaged resulting in too little thyroid hormone production or hypothyroidism. Some patients may experience "swings" in hormone levels that can progress rapidly from hyper-to-hypothyroid (sometimes mistaken as severe moodswings, or even being bipolar, before the proper clinical diagnosis is made). Some patients may experience these "swings" over a longer period of time, over days or weeks or even months. Hashimoto's is more common in females than males, usually appearing after the age of 30, and tends to run in families meaning it can be seen as a genetic disease. Also more common in individuals with Hashimoto's Thyroiditis are type 1 diabetes and celiac disease.

Postpartum thyroiditis occurs in some females following the birth of a child. After delivery, the gland becomes inflamed and the condition initially presents with overactivity of the gland followed by underactivity. In some cases, the gland may recover with time and resume its functions. In others it may not. The etiology is not always known, but can sometimes be attributed to autoimmunity, such as Hashimoto's Thyroiditis or Graves' Disease.

Cancers

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

Non-cancerous nodules

Many individuals may find the presence of thyroid nodules in the neck. The majority of these thyroid nodules are benign (non cancerous). The presence of a thyroid nodule does not mean that one has thyroid disease. Most thyroid nodules do not cause any symptoms, and most are discovered on an incidental examination. Doctors usually perform a needle aspiration biopsy of the thyroid to determine the status of the nodules. If the nodule is found to be non-cancerous, no other treatment is required. If the nodule is suspicious then surgery is recommended..

Other disorders

Limited research shows that seasonal allergies may trigger episodes of hypo- or hyperthyroidism.

A ectopic thyroid is an entire or parts of the thyroid located in another part of the body than what is the usual case.

Physiology

The primary function of the thyroid is production of the hormones triiodothyronine (T₃), thyroxine (T₄), and calcitonin. Up to 80% of the T₄ is converted to T₃ by peripheral organs such as the liver, kidney and spleen. T₃ is several times more powerful than T₄, which is largely a prohormone, perhaps four or even ten times more active.

T₃ and T₄ production and action

s T₃ and T₄.]] s, as seen on an individual thyroid follicular cell: - Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis. - Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I^-) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms. - This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner. - In the colloid, iodide (I^-) is oxidized to iodine (I⁰) by an enzyme called thyroid peroxidase. - Iodine (I⁰) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues). - In conjugation, adjacent tyrosyl residues are paired together. - The entire complex re-enters the follicular cell by endocytosis. - Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules, which enters the blood by largely unknown mechanisms. ]] Thyroxine (T₄) is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (Tg). Iodine is captured with the "iodine trap" by the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO) and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on Tg, and on free tyrosine. Upon stimulation by the thyroid-stimulating hormone (TSH), the follicular cells reabsorb Tg and cleave the iodinated tyrosines from Tg in lysosomes, forming T₄ and T₃ (in T₃, one iodine atom is absent compared to T₄), and releasing them into the blood. Deiodinase enzymes convert T₄ to T₃. Thyroid hormone secreted from the gland is about 80-90% T₄ and about 10-20% T₃. A transport protein that seems to be important for T₄ transport across the blood-brain barrier (OATP1C1) has been identified. A second transport protein (MCT8) is important for T₃ transport across brain cell membranes. |- | Serum thyrotropin/thyroid-stimulating hormone || TSH || 0.3–3.0 μU/ml |- | Free thyroxine || FT₄ ||| 7–18 ng/l = 0.7–1.8 ng/dl |- | Serum triiodothyronine || T₃ || 0.8–1.8 μg/l = 80–180 ng/dl |- | Radioactive iodine-123 uptake || RAIU || 10–30% |- | Radioiodine scan (gamma camera) || N/A || N/A - thyroid contrasted images |- | Free thyroxine fraction || FT4F || 0.03–0.005% |- | Serum thyroxine || T₄ || 46–120 μg/l = 4.6–12.0 μg/dl |- | Thyroid hormone binding ratio || THBR || 0.9–1.1 |- | Free thyroxine index || FT4I || 4–11 |- | Free triiodothyronine l || FT₃ || 230–619 pg/d |- | Free T3 Index || FT3I || 80–180 |- | Thyroxine-binding globulin || TBG || 12–20 ug/dl T4 +1.8 μg |- | TRH stimulation test || Peak TSH || 9–30 μIU/ml at 20–30 min. |- | Serum thyroglobulin l || Tg || 0-30 ng/m |- | Thyroid microsomal antibody titer || TMAb || Varies with method |- | Thyroglobulin antibody titer || TgAb || Varies with method |}

μU/ml = mU/l, microunit per milliliter

ng/dl, nanograms per deciliter

μg, micrograms

pg/d, picograms per day

μIU/ml = mIU/l, micro-international unit per milliliter

See for more information on medical units of measure

Significance of iodine

In areas of the world where iodine is lacking in the diet the thyroid gland can become considerably enlarged, a condition called endemic goiter. Pregnant women on a diet that is severely deficient of iodine can give birth to infants who can present with thyroid hormone deficiency (congenital hypothyroidism), manifesting in problems of physical growth and development as well as brain development (a condition referred to as endemic cretinism). In many developed countries, newborns are routinely tested for congenital hypothyroidism as part of newborn screening. Children with congenital hypothyroidism are treated supplementally with levothyroxine, which facilitates normal growth and development.

Thyroxine is critical to the regulation of metabolism and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; in contrast, administering thyroxine will trigger metamorphosis.

Because the thyroid concentrates this element, it also concentrates the various radioactive isotopes 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 non-radioactive iodine, taken in the form of potassium iodide tablets. One consequence of the Chernobyl disaster was an increase in thyroid cancers in children in the years following the accident.

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

As with most substances, either too much or too little can cause problems. Recent studies on some populations are showing that excess iodine intake could cause an increased prevelence of autoimmune thyroid disease, resulting in permanent hypothyroidism.

History

There are several findings that evidence a great interest for thyroid disorders just in the Medieval Medical School of Salerno (12th century). Rogerius Salernitanus, the Salernitan surgeon and author of "Post mundi fabricam" (around 1180) was considered at that time the surgical text par excellence all over Europe. In the chapter "De bocio" of his magnum opus, he describes several pharmacological and surgical cures, some of which nowadays are reappraised quite scientifically effective.

In modern times, the thyroid was first identified by the anatomist Thomas Wharton (whose name is also eponymised in Wharton's duct of the submandibular gland) in 1656.

Thyroxine was identified only in the 19th century.

In animals

The thyroid gland is found in all vertebrates. In fish, it is, in general, located below the gills and is not always divided into distinct lobes. However, in some teleosts, patches of thyroid tissue are found elsewhere in the body, associated with the kidneys, spleen, heart, or eyes.

In tetrapods, the thyroid is always found somewhere in the neck region. In most tetrapod species, there are two paired thyroid glands - that is, the right and left lobes are not joined together. However, there is only ever a single thyroid gland in most mammals, and the shape found in humans is common to many other species.

See also

Thyroid disease

Thyroid disease in pregnancy

Academy of Clinical Thyroidologists

References

External links

EndocrineWeb.com for more information on thyroid disease, hormones, and surgery

American Thyroid Association (Thyroid Information and professional organization)

"Thyroid Gland"

Category:Glands Category:Endocrine system Category:Head and neck