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14-September-2008 18:02:48 - Thyroid June 2008 Thyroid Endocrine system Thyroid and parathyroid. Latin glandula thyroidea Gray's subject #272 1269 System endocinal jubachina system Artery superior thyroid artery, inferior thyroid artery, thyreoidea ima Vein superior thyroid vein, middle thyroid vein, inferior thyroid vein Nerve middle cervical ganglion, inferior cervical ganglion Precursor 4th Branchial pouch MeSH Thyroid+Gland Dorlands/Elsevier g_06/12392768 For other uses, see Thyroid cartilage. The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck inferior to below the thyroid cartilage also known as the Adam's apple in men and at approximately the same level as the cricoid cartilage. The thyroid controls how quickly the body burns energy, makes proteins, and how sensitive the body should be to other hormones. The thyroid participates in these processes by producing thyroid hormones, principally thyroxine T4 and triiodothyronine T3. These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. Iodine is an essential component of both T3 and T4. The thyroid also produces the hormone calcitonin, which plays a role in calcium homeostasis. The thyroid is controlled by the hypothalamus and pituitary. The gland gets its name from the Greek word for door, after the shape of the related thyroid cartilage. Hyperthyroidism overactive thyroid and hypothyroidism underactive thyroid are the most common problems of the thyroid gland. Contents 1 Anatomy 1.1 Embryological development 1.2 Histology 2 Physiology 2.1 T3 and T4 production and action 2.2 T3 and T4 regulation 2.3 Calcitonin 2.4 Significance of iodine 3 Diseases 3.1 Hyper- and hypofunction 3.2 Anatomical problems 3.3 Tumors 3.4 Deficiencies 4 Diagnosis 4.1 Blood tests 4.2 Ultrasound 4.3 Radioiodine scanning and uptake 4.4 Biopsy 5 Treatment 5.1 Medical treatment 5.2 Surgery 5.3 Radioiodine therapy 6 History 7 Additional images 8 See also 9 References 10 External links 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 with 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 the fourth to sixth tracheal ringcitation needed. It is difficult to demarcate the gland's upper and lower border with vertebral levels as 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. Posteriorly, 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 Berry12. In variable extent, Zuckerkandl's tubercle, a pyramidal extension of the thyroid lobe, is present at the most posterior side of the lobe34. 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 pregnancycitation needed. 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 aortic arch. 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 sympathetic nerve input from the superior cervical ganglion and the cervicothoracic ganglion of the sympathetic trunkcitation needed, and by parasympathetic nerve input from the superior laryngeal nerve and the recurrent laryngeal nerve. Embryological development This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. January 2008 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 latter indicated by the foramen cecum. Subsequently the thyroid 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. Follicles of the thyroid begin to make colloid in the 11th week and thyroxine by the 18th week. Floor of pharynx of embryo between 18 and 21 days. Histology This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. January 2008 At the microscopic level, there are three primary features of the thyroid: Feature Description Follicles The thyroid is composed of spherical follicles that selectively absorb iodine as iodide ions, I- from the blood for production of thyroid hormones. Twenty-five percent of all the body's iodide ions are in the thyroid gland. Inside the follicles, colloids rich in a protein called thyroglobulin serve as a reservoir of materials for thyroid hormone production and, to a lesser extent, act as a reservoir for the hormones themselves. Thyroid epithelial cells or follicular cells The follicles are surrounded by a single layer of thyroid epithelial cells, which secrete T3 and T4.The epithelial cells range between low columnar to cuboidal cells when the gland inactive.In active gland the epithelial cells become tall columnar cells. Parafollicular cells or C cells Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells, which secrete calcitonin. Physiology The primary function of the thyroid is production of the hormones thyroxine T4, triiodothyronine T3, and calcitonin. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver, kidney and spleen. T3 is about ten times more active than T4.5 T3 and T4 production and action 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 TPO6 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 proteolytically cleave the iodinated tyrosines from TG, forming T4 and T3 in T3, one iodine is absent compared to T4, and releasing them into the blood. Deiodinase enzymes convert T4 to T3.7 Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3.5 Cells of the brain are a major target for the thyroid hormones T3 and T4. Thyroid hormones play a particularly crucial role in brain development during pregnancy.8 A transport protein OATP1C1 has been identified that seems to be important for T4 transport across the blood brain barrier.9 A second transport protein MCT8 is important for T3 transport across brain cell membranes.9 In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. Only a very small fraction of the circulating hormone is free unbound - T4 0.03% and T3 0.3%. Only the free fraction 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 transcription2. T3 and T4 regulation The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone TSH, released by the anterior pituitary that is in turn released as a result of TRH release by the hypothalamus. 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 TRH, 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, rising levels of glucocorticoids and sex hormones estrogen and testosterone, and excessively high blood iodide concentration. Calcitonin An additional hormone produced by the thyroid contributes to the regulation of blood calcium levels. Parafollicular cells produce calcitonin in response to hypercalcemia. Calcitonin stimulates movement of calcium into bone, in opposition to the effects of parathyroid hormone PTH. However, calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid, but not the parathyroids. 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 have physical growth and development problems, and brain development can also 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 by analysis of a drop of blood. Children with thyroid hormone deficiency are treated by supplementation with synthetic thyroxine, which enables them to grow and develop normally. Because of the thyroid's selective uptake and concentration of what is a fairly rare element, it is 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 children in the years following the accident.10 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 mandatory. Potassium iodide and Sodium iodide are the most active forms of supplemental iodine. Diseases This article or section may require cleanup because it is in a list format that may be better presented using prose. You can help by converting this section to prose, if appropriate. ing help is available. June 2008 Hyper- and hypofunction Depending on the prescribed school of thought, affects between 2% and 20% of the population.11 Hypothyroidism underactivity Hashimoto's thyroiditis / thyroiditis Ord's thyroiditis Postoperative hypothyroidism Postpartum thyroiditis Silent thyroiditis Acute thyroiditis Iatrogenic hypothyroidism Hyperthyroidism overactivity Thyroid storm Graves-Basedow disease Toxic thyroid nodule Toxic nodular struma Plummer's disease Hashitoxicosis Iatrogenic hyperthyroidism De Quervain's thyroiditis inflammation starting as hyperthyroidism, can end as hypothyroidism Anatomical problems Goitre Endemic goitre Diffuse goitre Multinodular goitre Lingual thyroid Thyroglossal duct cyst Tumors Thyroid adenoma Thyroid cancer Papillary Follicular Medullary Anaplastic Lymphomas and metastasis from elsewhere rare Deficiencies Cretinism Medication linked to thyroid disease includes amiodarone, lithium salts, some types of interferon and IL-2. Diagnosis Blood tests The measurement of thyroid-stimulating hormone TSH levels is often used by doctors as a screening test. Elevated TSH levels can signify an inadequate thyroid 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; T4 and T3 levels may be determined with blood tests to confirm that their levels are decreased. Autoantibodies may be detected in various disease states anti-TG, anti-TPO, TSH receptor stimulating antibodies. There are two cancer markers for thyroid derived cancers. Thyroglobulin TG for well differentiated papillary or follicular adenocarcinoma, and the rare medullary thyroid cancer has calcitonin as the marker. Very infrequently, TBG and transthyretin levels may be abnormal; these are not routinely tested. To differentiate between duifferent types of hypothyroidism, a specific test may be used. Thyroid-releasing hormone TRH is injected into the body through a vein. This hormone is naturally secreted by the hypothalamus and stimulates the pituitary gland. The pituitary responds by releasing thyroid -stimulating hormone TSH. Large amounts of externally administered TRH can suppress the subsequent release of TSH. This amount of release-suppression is exaggerated in primary hypothyroidism, major depression, cocaine dependence, amphetamine dependence and chronic phencyclidine abuse. There is a failure to suppress in the manic phase of bipolar disorder. 12 Ultrasound Nodules of the thyroid may or may not be cancer. Medical ultrasonography can help determine their nature because some of the characteristics of benign and malignant nodules differ. The main characteristics of a thyroid nodule on high frequency thyroid ultrasound are as follows: Possible cancer Benign characteristics irregular border smooth borders hypoechoic less echogenic than the surrounding tissue hyperechoic microcalcifications - taller than wide shape on transverse study - significant intranodular blood flow by power Doppler - - comet tail artifact as sound waves bounce off intranodular colloid Ultrasonography is not always able to separate benign from malignant nodules with complete certainty. In suspicious cases, a tissue sample is often obtained by biopsy for microscopic examination. Radioiodine scanning and uptake Thyroid scintigraphy, imaging of the thyroid with the aid of radioactive iodine, usually iodine-123 123I, is performed in the nuclear medicine department of a hospital or clinic. Radioiodine collects in the thyroid gland before being excreted in the urine. While in the thyroid the radioactive emissions can be detected by a camera, producing a rough image of the shape a radiodine scan and tissue activity a radioiodine uptake of the thyroid gland. A normal radioiodine scan shows even uptake and activity throughout the gland. Irregularity can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive, different from the rest. For example, a nodule that is overactive hot to the point of suppressing the activity of the rest of the gland is usually a thyrotoxic adenoma, a surgically curable form of hyperthyroidism that is hardly ever malignant. In contrast, finding that a substantial section of the thyroid is inactive cold may indicate an area of non-functioning tissue such as thyroid cancer. The amount of radioactivity can be counted as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8 to 35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland as may occur with hypothyroidism or hyperthyroidism is usually reflected in decreased or increased radioiodine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism. Biopsy A medical biopsy refers to the obtaining of a tissue sample for examination under the microscope or other testing, usually to distinguish cancer from noncancerous conditions. Thyroid tissue may be obtained for biopsy by fine needle aspiration or by surgery. Needle aspiration has the advantage of being a brief, safe, outpatient procedure that is safer and less expensive than surgery and does not leave a visible scar. Needle biopsies became widely used in the 1980s, but it was recognized that accuracy of identification of cancer was good but not perfect. The accuracy of the diagnosis depends on obtaining tissue from all of the suspicious areas of an abnormal thyroid gland. The reliability of needle aspiration is increased when sampling can be guided by ultrasound, and over the last 15 years, this has become the preferred method for thyroid biopsy in North America. 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. Percutaneous Ethanol Injections, PEI, for therapy of recurrent thyroid cysts, and metastatic thyroid cancer lymph nodes, as an alternative to the usual surgical method. Surgery Thyroid surgery is performed for a variety of reasons. A nodule or lobe of the thyroid is sometimes removed for biopsy or for the presence of an autonomously functioning adenoma causing hyperthyroidism. A large majority of the thyroid may be removed, a subtotal thyroidectomy, to treat the hyperthyroidism of Graves' disease, or to remove a goitre that is unsightly or impinges on vital structures. A complete thyroidectomy of the entire thyroid, including associated lymph nodes, is the preferred treatment for thyroid cancer. Removal of the bulk of the thyroid gland usually produces hypothyroidism, unless the person takes thyroid hormone replacement. Consequently, individuals who have undergone a total thyroidectomy are typically placed on thyroid hormone replacement for the remainder of their lives. Higher than normal doses are often administered to prevent recurrence. If the thyroid gland must be removed surgically, care must be taken to avoid damage to adjacent structures, the parathyroid glands and the recurrent laryngeal nerve. Both are susceptible to accidental removal and/or injury during thyroid surgery. The parathyroid glands produce parathyroid hormone PTH, a hormone needed to maintain adequate amounts of calcium in the blood. Removal results in hypoparathyroidism and a need for supplemental calcium and vitamin D each day. In the event the blood supply to any one of the parathyroid glands is endangered through surgery, the parathyroid glands involved may be re-implanted in surrounding muscle tissue. The recurrent laryngeal nerves 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 may cause paralysis of the vocal cords and their associated muscles, changing the voice quality. Radioiodine therapy Large goiters that cause symptoms, but do not harbor cancer, after evaluation, and biopsy of suspicious nodules can be treated by an alternative therapy with radioiodine. The iodine uptake can be high in countries with iodine deficiency, but low in iodine sufficient countries. The 1999 release of rhTSH thyrogen in the USA, can boost the uptakes to 50-60% allowing the therapy with iodine 131. The gland shrinks by 50-60%, but can cause hypothyroidism, and rarely pain syndrome cause by radiation thyroiditis that is short lived and treated by steroids. History There are several findings that evidence a great interest for thyroid disorders just in the Medieval Medical School of Salerno XII 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.13 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 1656.14 Thyroid hormone or thyroxin was identified only in the 19th century. Additional images Position of the Thyroid in Males and Females Section of the neck at about the level of the sixth cervical vertebra. Muscles of the neck. Anterior view. The arch of the aorta, and its branches. Superficial dissection of the right side of the neck, showing the carotid and subclavian arteries. Diagram showing common arrangement of thyroid veins. Sagittal section of nose mouth, pharynx, and larynx. Muscles of the pharynx, viewed from behind, together with the associated vessels and nerves. The position and relation of the esophagus in the cervical region and in the posterior mediastinum. Seen from behind. Section of thyroid gland of sheep. X 160. The thymus of a full-term fetus, exposed in situ. Thyoid histology See also Thymus Academy of Clinical Thyroidologists References ^ Yalçin B., Ozan H. feb 2006. Detailed investigation of the relationship between the inferior laryngeal nerve including laryngeal branches and ligament of Berry. Journal of the American College of Surgeons 202 2: 291-6. doi:10.1016/j.jamcollsurg.2005.09.025. PMID 16427555. ^ Lemaire, David 2005-05-27, eMedicine - Thyroid anatomy, http://www.emedicine.com/ent/topic532.htm. Retrieved on 19 January 2008 ^ Yalçin B, Poyrazoglu Y, Ozan H 2007. Relationship between Zuckerkandl's tubercle and the inferior laryngeal nerve including the laryngeal branches. Surg. Today 37 2: 109-13. doi:10.1007/s00595-006-3346-y. PMID 17243027. ^ Mirilas P, Skandalakis JE 2003. Zuckerkandl's tubercle: Hannibal ad Portas. J. Am. Coll. Surg 196 5: 796-801. doi:10.1016/S1072-75150201831-8. PMID 12742214. ^ a b The thyroid gland in Endocrinology: An Integrated Approach by Stephen Nussey and Saffron Whitehead 2001 Published by BIOS Scientific Publishers Ltd. ISBN 1-85996-252-1 . ^ Ekholm R, Bjorkman U 1997. Glutathione peroxidase degrades intracellular hydrogen peroxide and thereby inhibits intracellular protein iodination in thyroid epithelium. Endocrinology 138 7: 2871-2878. doi:10.1210/en.138.7.2871. PMID 9202230. ^ Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR 2002. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23 1: 38-89. doi:10.1210/er.23.1.38. PMID 11844744. ^ Kester MH, Martinez de Mena R, Obregon MJ, Marinkovic D, Howatson A, Visser TJ, Hume R, Morreale de Escobar G 2004. Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas. J Clin Endocrinol Metab 89 7: 3117-3128. doi:10.1210/jc.2003-031832. PMID 15240580. ^ a b Jansen J, Friesema ECH, Milici C, Visser TJ 2005. Thyroid hormone transporters in health and disease. Thyroid 15;757-768. PMID 16131319. ^ BBC NEWS | Science/Nature | Chernobyl children show DNA changes ^ 1 in Endocrinology: An Integrated Approach by Mary Shomon 2006 Published by About.com ^ Giannini AJ, Malone DA, Loiselle RH, Price WA 1987. Blunting of TSH response to TRH in chronic cocaine and phencyclidine abusers. J Clin Psychiatry 48 1: 25-6. PMID 3100509. ^ Bifulco M, Cavallo P 2007. Thyroidology in the medieval medical school of salerno. Thyroid 17 1: 39-40. doi:10.1089/thy.2006.0277. PMID 17274747. ^ Thomas Wharton at Who Named It External links American Thyroid Association Thyroid Information and professional organization Histology at KUMC epithel-epith03 Thyroid Gland New Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer from the American Thyroid Association Taskforce. Thyroid Disease Manager free online textbook Thyroid Disease Nuclear Medicine Information The Thyroid Foundation of America Education about Thyroid Disease v d e Human anatomy, endocrine system: endocrine glands Hypothalamic/ pituitary axes Thyroid axis Thyroid gland Parafollicular cell, Thyroid epithelial cell, Thyroid isthmus, Lobes of thyroid gland, Pyramid of thyroid Parathyroid gland Oxyphil cell, Chief cell Adrenal axis Adrenal gland Gonadal axis Testes - Ovaries - Corpus luteum Pineal gland Pinealocyte Islets of pancreas Alpha cell - Beta cell - Delta cell - PP cell - Epsilon cell Retrieved from http://en..org/wiki/Thyroid Categories: Glands | Endocrine system | Thyroid disease | Head and neckHidden categories: Articles needing additional references from June 2008 | All articles with statements | Articles with statements since January 2008 | Articles needing additional references from January 2008 | Cleanup from June 2008 | Articles with sections that need to be turned into prose Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages العربية ÄŒesky Dansk Deutsch Ελληνικά Español Euskara Français Hrvatski Italiano עברית Latina LatvieÅ¡u Lietuvių МакедонÑ?ки Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português РуÑ?Ñ?кий SlovenÄ?ina СрпÑ?ки / Srpski Suomi Svenska தமிழà¯? ไทย Tiếng Việt Türkçe ייִדיש 粵語 ä¸æ–‡ This page was last modified on 8 September 2008, at 19:4
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