The thyroid is the largest endocrine gland in the body. It is located in the neck and produces hormones, principally thyroxine, that regulate the rate of metabolism and have many other functions.

Anatomy

Gross anatomy

The thyroid is situated on the front side of the neck at the level of C5 to T1 vertebral bodies, just below the laryngeal prominence (Adam's apple), near the thyroid cartilage over the trachea but covered by layers of skin and muscle. The thyroid is quite large for an endocrine gland - 15-40 grams in adults- and butterfly-shaped: the wings correspond to the lobes and the body to the isthmus of the thyroid. Normally it is larger during menstruation and in pregnant women.

Blood supply

The thyroid gland is supplied by two arteries: the superior and inferior thyroid arteries. The superior thyroid artery is the first branch of the external carotid, and supplies mostly the upper half of the thyroid gland, while the inferior thyroid artery is the major branch of the thyrocervical trunk, which comes off of the subclavian artery. In 10% of people, there is also a thyroid ima artery that arises from the brachiocephalic trunk or the arch of the aorta. Lymph drainage follows the arterial supply.

There are three main veins that drain the thyroid. The superior, middle and inferior thyroid veins.

Histology of the thyroid

The gland is composed of spherical follicles that selectively absorb iodine (more accurately iodide ions, I^-) from the bloodstream and concentrate it for production of thyroid hormones. Twenty-five percent of all the body I^- is in the thyroid gland. The follicles are made of a single layer of thyroid epithelial cells, which secrete T3 and T4. Inside the follicles is a colloid which is rich in a protein called thyroglobulin. It serves as a reservoir of materials for thyroid hormone production and, to a lesser extent, a reservoir of the hormones themselves. The spaces between the thyroid follicle spheres are filled with the other type of thyroid cells, parafollicular cells or C cells, which secrete calcitonin.

Physiology

The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3, mostly produced by the liver through conversion of T4) and calcitonin.

T3 and T4 production and action

Thyroxine is synthetised by the follicular cells from the tyrosine residues of the protein called thyroglobulin (TG). Iodine, captured with the "iodine trap" is activated by the enzyme thyroid peroxidase (TPO) and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on TG. Upon stimulation by TSH (see below), the follicular cells reabsorb TG and proteolytically cleave the iodinated tyrosines from TG, combining them into T4 and T3 (in T3, one iodine is absent compared to T4), and releasing them into the blood.

In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. Only the free fraction (not bound to these proteins) has hormonal activity. As with the steroid hormones and retinoic acid, thyroid hormones cross the cell membrane and bind to intracellular receptors (α₁, α₂, β₁ and β₂), which act alone, in pairs or together with the retinoid X-receptor as transcription factors to modulate DNA transcription[1].

T3 and T4 regulation

The production of thyroxine is regulated by thyroid-stimulating hormone (TSH), released by the pituitary. The thyroid and thyrotropes form a negative feedback loop: TSH production is suppressed when the T4 levels are high, and vice versa. The TSH production itself is modulated by thyrotropin-releasing hormone, which is produced by the hypothalamus and secreted at an increased rate in situations such as cold (in which an accelerated metabolism would generate more heat). TSH production is blunted by somatostatin (SRIH).

Calcitonin

Calcitonin, produced by the parafollicular cells, is produced in response to hypercalcemia and plays a role in the calcium metabolism; it is the functional opposite of parathyroid hormone, but exerts its influence mainly on bone. Its relatively small role is signified by the fact that after removal of the thyroid, calcium levels typically remain stable.

The significance of iodine

In areas of the world where iodine - essential for the production of thyroxine, which contains four iodine atoms - is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre.

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

In humans, children born with thyroid hormone deficiency will not grow well, and brain development can be severely impaired, in the condition referred to as cretinism. Newborn children in many developed countries are now routinely tested for thyroid hormone deficiency as part of newborn screening together with the Guthrie test; this is done by analysis of a small drop of blood from the child. Children with thyroid hormone deficiency are easily treated by supplementation with synthetic thyroxine, which enables them to grow and develop normally.

Because of the thyroid's selective uptake and extreme concentration of what is actually a fairly rare element, it is extremely sensitive to the effects of 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. While biological researchers making compounds labelled with iodine isotopes do this, in the wider world such preventive measures are usually not stockpiled before an accident, nor are they distributed adequately afterward - one consequence of the Chernobyl disaster was an increase in thyroid cancers in the years following the accident. [2]

Iodised salt is a very cheap and easy way of adding iodine to the diet. This has led to a reduction to almost zero of the indicence of cretinism in most developed countries, and some governments have made the ionidation of flour mandatory.

Diseases of the thyroid gland

Hyper- and hypofunction:

• Hypothyroidism
  • Hashimoto's thyroiditis / thyroiditis
  • Ord's thyroiditis
  • Postoperative hypothyroidism
  • Postpartum thyroiditis
  • Silent thyroiditis
  • Acute thyroiditis
  • Iatrogenic hypothyroidism
• Hyperthyroidism
  • Thyroid storm
  • Graves-Basedow disease
  • Toxic thyroid nodule
  • Toxic nodular struma (Plummer's disease)
  • Hashitoxicosis
  • Iatrogenic hyperthyroidism

Anatomical problems:

• Goitre
  • Endemic goitre
  • Diffuse goitre
  • Multinodular goitre
• Lingual thyroid
• Thryoglossal duct cyst

Tumors:

• Thyroid adenoma
• Thyroid cancer
  • Papillary
  • Follicular
  • Medullary
  • Anaplastic
• Lymphomas and metastasis from elsewhere (rare)

Medication linked to thyroid disease includes amiodarone, lithium salts, some types of interferon and IL-2.

Diagnosis

The measurement of thyroid-stimulating hormone (TSH) levels is often used by doctors as a screening test. Elevated TSH levels can signify an inadequate hormone production, while suppressed levels can point at excessive unregulated production of hormone. If TSH is abnormal, decreased levels of thyroid hormones T4 and T3 may be present; these may be determined to confirm this. Autoantibodies may be detected in various disease states (anti-TG, anti-TPO, TSH receptor stimulating antibodies). Infrequently, TBG and transthyretin levels may be abnormal; these are not routinely tested.

Nodules of the thyroid may require ultrasound to establish their nature, and fine needle aspiration may be performed. Scintigraphy with iodine-131 may reveal whether parts of the thyroid are abnormally active or inactive.

Treatment

Medical treatment

Levothyroxine is a stereoisomer of thyroxine which is degraded much slower and can be administered once daily in patients with hypothyroidism.

Graves' disease may be treated with the thioamide drugs propylthiouracil, carbimazole or methimazole, or rarely with Lugol's solution. Hyperthyroidism as well as thyroid tumors may be treated with radioactive iodine.

Thyroid surgery

If the thyroid gland must be removed surgically for any reason, care must be taken to avoid damage to the adjacent structures that are extremely susceptible to accidental removal and/or severence. In particular, the parathyroid glands, which produce parathormone (PTH) reside on the posterior wall of the thyroid gland, and the recurrent laryngeal nerves, which provide motor control for all external muscles of the larynx except for the cricothyroid muscle, also runs along the posterior thyroid. Accidental laceration of either of the two or both recurrent laryngeal nerves will lead to paralysis of the vocal cords and their associated muscles and a subsequent muting effect on the patient.

History

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. Thyroid hormone (or thyroxin) was only identified in the 19th century.

cs:Štítná žláza de:Schilddrüse es:Glándula tiroides fr:Thyroïde it:Tiroide he:בלוטת התריס lt:Skydliaukė nl:Schildklier ja:甲状腺 no:Skjoldbruskkjertel pl:Tarczyca pt:Tiróide fi:Kilpirauhanen