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See also the Discussion Page for other references listed by year and References on this current page. Pyramidal lobe of the thyroid gland and the thyroglossal duct remnant: a study using human fetal sections  "To investigate developmental changes in the thyroglossal duct, we observed serial sagittal sections of eight embryos crown-rump length CRL mm; approximately weeks of gestation as well as serial horizontal or cross-sections of 70 embryos and fetuses CRL mm; weeks.
In the sagittal sections, the thyroglossal duct was identified as a small sheet or mass of relatively large cells with vacuolization anterior, superior or inferior to the fourth pharyngeal arch artery. However, we found no continuous duct-like structure that reached the thyroid gland. T3 is more potent than T4, and many cells convert T4 to T3 through the removal of an iodine atom.
As shown in Figure 2 , low blood levels of T3 and T4 stimulate the release of thyrotropin-releasing hormone TRH from the hypothalamus, which triggers secretion of TSH from the anterior pituitary. Figure 2. Classic Negative Feedback Loop. A classic negative feedback loop controls the regulation of thyroid hormone levels. When T3 and T4 bind to intracellular receptors located on the mitochondria, they cause an increase in nutrient breakdown and the use of oxygen to produce ATP.
In addition, T3 and T4 initiate the transcription of genes involved in glucose oxidation. Although these mechanisms prompt cells to produce more ATP, the process is inefficient, and an abnormally increased level of heat is released as a byproduct of these reactions.
Adequate levels of thyroid hormones are also required for protein synthesis and for fetal and childhood tissue development and growth. They are especially critical for normal development of the nervous system both in utero and in early childhood, and they continue to support neurological function in adults. As noted earlier, these thyroid hormones have a complex interrelationship with reproductive hormones, and deficiencies can influence libido, fertility, and other aspects of reproductive function.
When levels of T3 and T4 hormones are excessive, this effect accelerates the heart rate, strengthens the heartbeat, and increases blood pressure. Because thyroid hormones regulate metabolism, heat production, protein synthesis, and many other body functions, thyroid disorders can have severe and widespread consequences. Disorders of the… Endocrine System: Iodine Deficiency, Hypothyroidism, and Hyperthyroidism As discussed above, dietary iodine is required for the synthesis of T3 and T4.
Marine fish and shrimp tend to have high levels because they concentrate iodine from seawater, but many people in landlocked regions lack access to seafood. Thus, the primary source of dietary iodine in many countries is iodized salt.
Dietary iodine deficiency can result in the impaired ability to synthesize T3 and T4, leading to a variety of severe disorders. As a result of this hyperstimulation, thyroglobulin accumulates in the thyroid gland follicles, increasing their deposits of colloid.
The accumulation of colloid increases the overall size of the thyroid gland, a condition called a goiter Figure 3. Thyroid hormones are then synthesized in the thyroid gland in the following stages Fig. Thyroid iodide transport Iodine I in food is absorbed in the form of iodide I- and travels to the thyroid gland in the boodstream. Iodide accumulates in thyroid follicular cells via sodium iodide symporter NIS; SLC5A5 channels in the basolateral membrane of these cells [ 9 ]. NIS is an intrinsic transmembrane protein that actively transports iodide together with sodium.
Ions such as perchlorate and pertechnetate are also transported to the thyroid gland by the same mechanisms and act as competitive inhibitors of iodide transport. Inside thyroid follicular cells, iodide rapidly diffuses to the apical membrane, where it is transported into colloid by pendrin PDS; SLC26A4 channels [ 9 ]. Thyroglobulin synthesis Thyroglobulin is a glycoprotein synthesized within the endoplasmic reticulum ER of thyroid follicular cells; it forms exocytotic vesicles that migrate into the colloid via the apical membrane [ 10 , 11 ].
The tyrosine residues on thyroglobulin are used as substrates for the synthesis of thyroid hormone [ 11 ]. Oxidation and organification Iodide that has been transported to colloid undergoes oxidation to iodine, which is then covalently bound organified to the tyrosine residues in thyroglobulin to form monoiodotyrosine MIT and diiodotyrosine DIT [ 10 ]. The oxidation of iodide is catalyzed by thyroid peroxidase TPO , and hydrogen peroxide H2O2 is required for this reaction [ 12 ].
These reactions are also catalyzed by TPO [ 10 ]. Endocytosis of colloid and hormone release To secrete T4 and T3, thyroglobulin is endocytosed by thyroid follicular cells in the form of colloid droplets. T4 and T3 are then secreted into the blood.
Recycling of iodide DIT and MIT released following the hydrolysis of thyroglobulin are converted into free iodide and tyrosine by iodotyrosine deiodinase IYD also known as iodotyrosine dehalogenase 1 DEHAL1 , and the free iodide and tyrosine are then utilized inside of follicular cells [ 16 ].
The genetic causes of thyroid dyshormonogenesis are summarized in Table 1 and in the following sections, which describe the roles of genes involved in the thyroid hormone biosynthesis pathway. NIS SLC5A5 mutations: basolateral iodide transport defect NIS is a transmembrane domain glycoprotein that mediates active iodide transport in various tissues, such as the thyroid gland, salivary glands, stomach, lactating breasts, and small intestine [ 17 ].
The first case of CH caused by an iodide transport defect was described by Stanbury and Chapman in [ 18 ]. Fujiwara et al. Clinically, these mutations cause hypothyroidism accompanied by goiter with eutopic thyroid on thyroid ultrasonography but show low or absent radioactive iodine uptake RAIU in thyroid scintigraphy [ 21 ]. In addition, the stomach and salivary glands, which also contain NIS, are unable to uptake radioiodine [ 5 ].
Variation in the extent of hypothyroidism is related to a residual in vitro activity of mutant NIS [ 22 ]. In patients with residual NIS activity, thyroid function is improved by iodide supplementation; accordingly, iodide supplementation alone or in combination with L-T4 replacement is an appropriate treatment approach [ 1 ].
PDS SLC26A4 mutations: apical iodide transport defect Pendred syndrome Pendrin is a multifunctional anion exchanger expressed in the thyroid, inner ear, and kidney; in the thyroid, pendrin is located in the apical membrane of follicular cells and is thought to mediate apical iodide transport [ 23 ]. Pendrin is encoded by the SLC26A4 gene. Homozygous or compound heterozygous mutations in SLC26A4 can cause Pendred syndrome [ 24 ], an autosomal recessive disease characterized by congenital bilateral sensorineural deafness and goiter and the most common cause of syndromic deafness [ 24 ].
However, not all mutations in SLC26A4 cause Pendred syndrome and approximately half of mutations cause deafness with normal thyroid function nonsyndromic hearing loss with familial enlarged vestibular aqueduct or DFNB4 [ 1 ].
Hypothyroidism in Pendred syndrome is usually mild and often undetected in neonatal screening [ 25 ]. Goiter typically develops in childhood, but cases of congenital goiter have also been reported [ 26 ].
Iodide intake affects the thyroid phenotype, and congenital goiter is more common in iodine-deficient areas [ 5 ]. Although the perchlorate discharge test is usually positive, some patients show a normal test [ 27 ]. TG mutations: thyroglobulin synthesis defect Thyroglobulin is the most abundantly expressed large homodimeric glycoprotein in the thyroid and acts as a matrix for the synthesis of thyroid hormone [ 11 ]. Thyroglobulin defects caused by mutations in TG are autosomal recessive and show a diverse clinical spectrum, ranging from a euthyroid state to severe hypothyroidism [ 11 ].Diagrammatic view of sagittal and transverse views of the pharyngeal regions of a human embryo during the fifth week of gestation, showing the endodermal pharyngeal pouches and mesodermal pharyngeal more Most patients show severe hypothyroidism and congenital goiter [ 5 ]. Hypothyroidism in infancy and childhood Clinical Case 3.
Hypothyroidism produces many signs and symptoms, as shown in the figure below. Others are thought to result from infections and give rise to very different clinical features. Other iodine deficiency disorders include impaired growth and development, decreased fertility, and prenatal and infant death. These findings suggested that iodination of lipids impairs H2O2 production and, therefore, decreases further Tg iodination. The gland is butterfly shaped and composed of two lobes.
Other causes include drug-induced excess of iodine, particularly from amiodarone , an antiarrhythmic medication ; an excess caused by the preferential uptake of iodine by the thyroid following iodinated contrast imaging ; or from pituitary adenomas which may cause an overproduction of thyroid stimulating hormone.
During the fetal period, cells of the developing brain are a major target for thyroid hormones, which play a crucial role in brain maturation. This has been attributed to generation of free radicals during oxidation TPO synthesized on polysomes is inserted in the membrane of the endoplasmic reticulum and undergoes core glycosylation. From Pitt-Rivers, R. If there is no involvement of the eyes, then use of radioactive isotopes to ablate the gland may be considered.
It is very unusual for thyroid cancers to present with other symptoms, although in some cases cancer may cause hyperthyroidism.