Materiały źródłowe

• #1 Goiter – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562161/

  Several pathogenic mechanisms can cause goiter. It can be caused by iodine deficiency, which is often seen in countries that do not have a public health intervention to prevent iodine deficiency. […] Inflammatory disorders of the thyroid gland such as autoimmune thyroiditis, postpartum thyroiditis, silent thyroiditis, radiation thyroiditis, subacute thyroiditis, and suppurative thyroiditis can cause thyroid enlargement, hence goiter. […] Enlargement of thyroid, i.e. goiter is an adaptive reaction of thyroid follicular cells to any process that blocks thyroid hormone production. The most common cause of goiter is iodine deficiency. […] Goiters have various morphological, hormonal, and clinical presentations and not all causes of goiter can be attributed to iodine deficiency. Genetic, demographic, and environmental factors are also responsible for the development of goiter.

• #2 Goiter | American Thyroid Association

  https://www.thyroid.org/goiter/

  The term goiter simply refers to the abnormal enlargement of the thyroid gland. A goiter indicates there is a condition present which is causing the thyroid to grow abnormally. […] One of the most common causes of goiter formation worldwide is iodine deficiency. The primary activity of the thyroid gland is to concentrate iodine from the blood to make thyroid hormone. The gland cannot make enough thyroid hormone if it does not have enough iodine. Therefore, with iodine deficiency the individual will become hypothyroid. Consequently, the pituitary gland in the brain senses the thyroid hormone level is too low and sends a signal to the thyroid. This signal is called thyroid stimulating hormone (TSH). As the name implies, this hormone stimulates the thyroid to produce thyroid hormone and to grow in size. This abnormal growth in size produces what is termed a goiter. Thus, iodine deficiency is one cause of goiter development.

• #3 Goiter: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/120034-overview

  The thyroid gland is controlled by thyroid-stimulating hormone (TSH; also known as thyrotropin), secreted from the pituitary gland, which in turn is influenced by the thyrotropin-releasing hormone (TRH) from the hypothalamus. TSH permits growth, cellular differentiation, and thyroid hormone production and secretion by the thyroid gland. Thyrotropin acts on TSH receptors located on the thyroid gland. Thyroid hormones are synthesized from iodination of tyrosine. The iodine is transported from plasma into the thyroid cell via a sodium-iodide symporter. This is an active process resulting in an intracellular iodine level exceeding 20 times the plasma iodine level. This iodine transport activity is controlled by TSH. […] Interference with this TRH-TSH thyroid hormone axis causes changes in the function and structure of the thyroid gland. Stimulation of the TSH receptors of the thyroid by TSH, TSH-receptor antibodies, or TSH receptor agonists, such as chorionic gonadotropin, may result in a diffuse goiter. When a small group of thyroid cells, inflammatory cells, or malignant cells metastatic to the thyroid is involved, a thyroid nodule may develop.

• #4 Goiter pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Goiter_pathophysiology

  When the TRH-TSH thyroid hormone axis is interfered, it results in the structural and functional changes of the thyroid gland. […] Increased TSH production is triggered by a deficiency in thyroid hormone synthesis or intake. […] In order to normalize thyroid hormone levels, the increase in TSH leads to increased cellularity and hyperplasia of the thyroid gland and when this process is continuous, it leads to goiter. […] Thyroid hormone deficiency may occur secondary to iodine deficiency, inborn errors of thyroid hormone synthesis and goitrogens. […] Goiters may form as a result of many TSH receptor agonists. The TSH receptor gets stimulated under the following conditions: Adenoma of the pituitary, Adenoma of the hypothalamus, Pituitary resistance to thyroid hormone, TSH receptor antibodies, Tumors producing hCG (human chorionic gonadotropin).

• #5 Goiter: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/120034-overview

  The thyroid gland is controlled by thyroid-stimulating hormone (TSH; also known as thyrotropin), secreted from the pituitary gland, which in turn is influenced by the thyrotropin-releasing hormone (TRH) from the hypothalamus. TSH permits growth, cellular differentiation, and thyroid hormone production and secretion by the thyroid gland. Thyrotropin acts on TSH receptors located on the thyroid gland. Thyroid hormones are synthesized from iodination of tyrosine. The iodine is transported from plasma into the thyroid cell via a sodium-iodide symporter. This is an active process resulting in an intracellular iodine level exceeding 20 times the plasma iodine level. This iodine transport activity is controlled by TSH. […] Interference with this TRH-TSH thyroid hormone axis causes changes in the function and structure of the thyroid gland. Stimulation of the TSH receptors of the thyroid by TSH, TSH-receptor antibodies, or TSH receptor agonists, such as chorionic gonadotropin, may result in a diffuse goiter. When a small group of thyroid cells, inflammatory cells, or malignant cells metastatic to the thyroid is involved, a thyroid nodule may develop.

• #6 Goiter defination ,pathogenesis,classification.pptx

  https://www.slideshare.net/slideshow/goiter-defination-pathogenesisclassificationpptx-254564905/254564905

  Goiter/Goitre Non specific term to indicate diffuse enlargement of thyroid gland. […] Pathophysiology:TRH-TSH thyroid hormone axis The thyroid gland is controlled byTSH secreted from the pituitary gland, Pituitary is stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. TSH acts on TSH receptors located on the thyroid gland TSH permits growth, cellular differentiation, and thyroid hormone production and secretion by the thyroid gland. Serum thyroid hormones levothyroxine and triiodothyronine feed back to the pituitary, regulating TSH production […] Stimulation of the TSH receptors of the thyroid by TSH, TSH-receptor antibodies, or TSH receptor agonists, such as chorionic gonadotropin, may result in a diffuse goiter. When a small group of thyroid cells, inflammatory cells, or malignant cells metastatic to the thyroid is involved, a thyroid nodule may develop.

• #7 Goitre – Wikipedia

  https://en.wikipedia.org/wiki/Goitre

  A goitre (British English), or goiter (American English), 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 most common cause for goitre is iodine deficiency, commonly seen in countries that scarcely use iodized salt. Selenium deficiency is also considered a contributing factor. In countries that use iodized salt, Hashimoto’s thyroiditis is the most common cause. […] Goitre can also result from cyanide poisoning, which is particularly common in tropical countries where people eat the cyanide-rich cassava root as the staple food. […] Hyperplasia of thyroid to compensate for decreased efficacy can cause hypothyroidism.

• #8 Goiter – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562161/

  Several pathogenic mechanisms can cause goiter. It can be caused by iodine deficiency, which is often seen in countries that do not have a public health intervention to prevent iodine deficiency. […] Inflammatory disorders of the thyroid gland such as autoimmune thyroiditis, postpartum thyroiditis, silent thyroiditis, radiation thyroiditis, subacute thyroiditis, and suppurative thyroiditis can cause thyroid enlargement, hence goiter. […] Enlargement of thyroid, i.e. goiter is an adaptive reaction of thyroid follicular cells to any process that blocks thyroid hormone production. The most common cause of goiter is iodine deficiency. […] Goiters have various morphological, hormonal, and clinical presentations and not all causes of goiter can be attributed to iodine deficiency. Genetic, demographic, and environmental factors are also responsible for the development of goiter.

• #9 Goiter – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562161/

  Iodine deficiency leads to subtle decreases in thyroid hormone production with T4 and T3 levels remaining in the reference range. The decrease of thyroid hormone levels from baseline increases TSH secretion from the pituitary gland. Increased demand for thyroid hormones due to physiological requirements like adolescence or pregnancy also leads to pituitary stimulation and increased TSH secretion. […] The increased TSH causes increased cellularity and hyperplasia of the thyroid gland. The thyroid follicular cells are stimulated and contribute to follicular hyperplasia and thyroid enlargement. […] Goiter can be the initial symptom of autoimmune thyroid disease. In Hashimotos thyroiditis thyroid enlarges gradually and can be detected by inspection, palpation, or ultrasonography. […] The most common cause of diffuse toxic goiter is Graves disease, an autoimmune thyroid disease. Patients with diffuse toxic goiter have a diffusely enlarged, vascular gland.

• #10 Multinodular Goiter: Pathogenesis and Management | Oncohema Key

  https://oncohemakey.com/multinodular-goiter-pathogenesis-and-management/

  A decrease in blood iodine levels leads to a decrease in thyroxine levels (T4), which in turn stimulates the secretion of TSH, in an effort to enhance iodine uptake and restore T4 blood levels. […] In turn, TSH also stimulates thyroid follicular cell hyperplasia and hypertrophy. […] Subsequently, thyroid nodules may become autonomous and secrete thyroid hormones independently of TSH due to activating mutations of the thyrotropin receptor. […] The pathogenesis of MNG has also been associated with alterations in the expression of proteins involved in thyrocyte proliferation and in the regulation of TSH receptor, such as Fas and DREAM (downstream regulatory element antagonist modulator), respectively. […] TSH is the most important growth factor involved in the pathogenesis of nodular goiter.

• #11 A Review of the Pathogenesis and Management of Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/46424

  Multinodular goiter (MNG) is a clinicopathological entity characterized by an increased volume of the thyroid gland with formation of nodules. […] The pathogenesis of MNG encompasses processes of diffuse follicular hyperplasia, focal nodular proliferation and eventual acquisition of functional automaticity. The development of MNG is a result of long-term exposure of the thyroid gland to proliferative stimuli, such as iodine deficiency, goitrogens and inborn error of thyroid hormone synthesis. All of the above results in insufficient thyroid hormone production and stimulate pituitary secretion of thyroid stimulating hormone (TSH). […] TSH is a glycoprotein with stimulatory effect on the trophic and iodine metabolism pathway in the thyroid follicular cells. TSH binding to the cell membrane G protein-coupled receptor activates the cAMP and phospholipase C signalling pathways, which in turn upregulates the process of iodine uptake and organification, thyroglobulin synthesis, iodotyrosine coupling and iodothyronine (T3, T4) secretion, leading to a short-term response in thyroid hormone production. […] In the long-term, TSH also stimulates proliferation of follicular cells to increase the functional mass of thyroid gland. Clinically, TSH stimulation results in enlargement of thyroid gland, increased radio-iodine uptake and increased T4 and T3 levels.

• #12 Goitre – Wikipedia

  https://en.wikipedia.org/wiki/Goitre

  A goitre (British English), or goiter (American English), 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 most common cause for goitre is iodine deficiency, commonly seen in countries that scarcely use iodized salt. Selenium deficiency is also considered a contributing factor. In countries that use iodized salt, Hashimoto’s thyroiditis is the most common cause. […] Goitre can also result from cyanide poisoning, which is particularly common in tropical countries where people eat the cyanide-rich cassava root as the staple food. […] Hyperplasia of thyroid to compensate for decreased efficacy can cause hypothyroidism.

• #13 Goiter | American Thyroid Association

  https://www.thyroid.org/goiter/

  Hashimotos thyroiditis is a more common cause of goiter formation in the US. This is an autoimmune condition in which there is destruction of the thyroid gland by ones own immune system. As the gland becomes more damaged, it is less able to make adequate supplies of thyroid hormone. The pituitary gland senses a low thyroid hormone level and secretes more TSH to stimulate the thyroid. This stimulation causes the thyroid to grow, which may produce a goiter. […] Another common cause of goiter is Graves disease. In this case, ones immune system produces a protein, called thyroid stimulating immunoglobulin (TSI). As with TSH, TSI stimulates the thyroid gland to enlarge producing a goiter. However, TSI also stimulates the thyroid to make too much thyroid hormone (causes hyperthyroidism). Since the pituitary senses too much thyroid hormone, it stops secreting TSH. In spite of this the thyroid gland continues to grow and make thyroid hormone. Therefore, Graves disease produces a goiter and hyperthyroidism.

• #14 Goiter | American Thyroid Association

  https://www.thyroid.org/goiter/

  Hashimotos thyroiditis is a more common cause of goiter formation in the US. This is an autoimmune condition in which there is destruction of the thyroid gland by ones own immune system. As the gland becomes more damaged, it is less able to make adequate supplies of thyroid hormone. The pituitary gland senses a low thyroid hormone level and secretes more TSH to stimulate the thyroid. This stimulation causes the thyroid to grow, which may produce a goiter. […] Another common cause of goiter is Graves disease. In this case, ones immune system produces a protein, called thyroid stimulating immunoglobulin (TSI). As with TSH, TSI stimulates the thyroid gland to enlarge producing a goiter. However, TSI also stimulates the thyroid to make too much thyroid hormone (causes hyperthyroidism). Since the pituitary senses too much thyroid hormone, it stops secreting TSH. In spite of this the thyroid gland continues to grow and make thyroid hormone. Therefore, Graves disease produces a goiter and hyperthyroidism.

• #15 Goiter | American Thyroid Association

  https://www.thyroid.org/goiter/

  Hashimotos thyroiditis is a more common cause of goiter formation in the US. This is an autoimmune condition in which there is destruction of the thyroid gland by ones own immune system. As the gland becomes more damaged, it is less able to make adequate supplies of thyroid hormone. The pituitary gland senses a low thyroid hormone level and secretes more TSH to stimulate the thyroid. This stimulation causes the thyroid to grow, which may produce a goiter. […] Another common cause of goiter is Graves disease. In this case, ones immune system produces a protein, called thyroid stimulating immunoglobulin (TSI). As with TSH, TSI stimulates the thyroid gland to enlarge producing a goiter. However, TSI also stimulates the thyroid to make too much thyroid hormone (causes hyperthyroidism). Since the pituitary senses too much thyroid hormone, it stops secreting TSH. In spite of this the thyroid gland continues to grow and make thyroid hormone. Therefore, Graves disease produces a goiter and hyperthyroidism.

• #16 Goiter – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562161/

  Iodine deficiency leads to subtle decreases in thyroid hormone production with T4 and T3 levels remaining in the reference range. The decrease of thyroid hormone levels from baseline increases TSH secretion from the pituitary gland. Increased demand for thyroid hormones due to physiological requirements like adolescence or pregnancy also leads to pituitary stimulation and increased TSH secretion. […] The increased TSH causes increased cellularity and hyperplasia of the thyroid gland. The thyroid follicular cells are stimulated and contribute to follicular hyperplasia and thyroid enlargement. […] Goiter can be the initial symptom of autoimmune thyroid disease. In Hashimotos thyroiditis thyroid enlarges gradually and can be detected by inspection, palpation, or ultrasonography. […] The most common cause of diffuse toxic goiter is Graves disease, an autoimmune thyroid disease. Patients with diffuse toxic goiter have a diffusely enlarged, vascular gland.

• #17 Goiter – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562161/

  The follicular cells are hypertrophic and hyperplastic, and lymphocytes and plasma cells infiltrate into the gland and group into lymphoid follicles. Antibodies (TSI: thyroid-stimulating immunoglobulin) are directed towards the thyroid-stimulating hormone receptors that are present on follicular cells. This stimulation of the receptors leads to the production of increased T4 and T3.

• #18 Graves’ disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/graves-disease/symptoms-causes/syc-20356240

  Graves’ disease is caused by the body’s disease-fighting immune system not working correctly. Experts don’t know why this happens. […] The immune system makes antibodies that target viruses, bacteria or other foreign substances. In Graves’ disease, the immune system makes an antibody to one part of the cells in the hormone-making gland in the neck, called the thyroid gland. […] A tiny gland at the base of the brain, called the pituitary gland, makes a hormone that controls the thyroid gland. The antibody linked with Graves’ disease is called thyrotropin receptor antibody (TRAb). TRAb takes over the work of the pituitary hormone. That leads to more thyroid hormone in the body than the body needs. That condition is called hyperthyroidism. […] Thyroid eye disease, also called Graves’ ophthalmopathy, comes from a buildup of certain carbohydrates in the muscles and tissues behind the eyes. The cause isn’t known. It may involve the same antibody that can cause the thyroid gland to not work correctly.

• #19 A Review of the Pathogenesis and Management of Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/46424

  Multinodular goiter (MNG) is a clinicopathological entity characterized by an increased volume of the thyroid gland with formation of nodules. […] The pathogenesis of MNG encompasses processes of diffuse follicular hyperplasia, focal nodular proliferation and eventual acquisition of functional automaticity. The development of MNG is a result of long-term exposure of the thyroid gland to proliferative stimuli, such as iodine deficiency, goitrogens and inborn error of thyroid hormone synthesis. All of the above results in insufficient thyroid hormone production and stimulate pituitary secretion of thyroid stimulating hormone (TSH). […] TSH is a glycoprotein with stimulatory effect on the trophic and iodine metabolism pathway in the thyroid follicular cells. TSH binding to the cell membrane G protein-coupled receptor activates the cAMP and phospholipase C signalling pathways, which in turn upregulates the process of iodine uptake and organification, thyroglobulin synthesis, iodotyrosine coupling and iodothyronine (T3, T4) secretion, leading to a short-term response in thyroid hormone production. […] In the long-term, TSH also stimulates proliferation of follicular cells to increase the functional mass of thyroid gland. Clinically, TSH stimulation results in enlargement of thyroid gland, increased radio-iodine uptake and increased T4 and T3 levels.

• #20 Multinodular Goiter – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK285569/

  Multinodular goiter (MNG) is the most common of all the disorders of the thyroid gland. MNG is the result of the genetic heterogeneity of follicular cells and apparent acquisition of new cellular qualities that become inheritable. […] The first comprehensive theory about the development of multinodular goiter was proposed by David Marine and studied further by Selwyn Taylor, and can be considered one of the classics in this field. Nodular goiter may be the result of any chronic low-grade, intermittent stimulus to thyroid hyperplasia. Supporting evidence for this view is circumstantial. David Marine first developed the concept, that in response to iodide deficiency, the thyroid first goes through a period of hyperplasia as a consequence of the resulting TSH stimulation, but eventually, possibly because of iodide repletion or a decreased requirement for thyroid hormone, enters a resting phase characterized by colloid storage and the histologic picture of a colloid goiter. Marine believed that repetition of these two phases of the cycle would eventually result in the formation of nontoxic multinodular goiter.

• #21 A Review of the Pathogenesis and Management of Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/46424

  Multinodular goiter (MNG) is a clinicopathological entity characterized by an increased volume of the thyroid gland with formation of nodules. […] The pathogenesis of MNG encompasses processes of diffuse follicular hyperplasia, focal nodular proliferation and eventual acquisition of functional automaticity. The development of MNG is a result of long-term exposure of the thyroid gland to proliferative stimuli, such as iodine deficiency, goitrogens and inborn error of thyroid hormone synthesis. All of the above results in insufficient thyroid hormone production and stimulate pituitary secretion of thyroid stimulating hormone (TSH). […] TSH is a glycoprotein with stimulatory effect on the trophic and iodine metabolism pathway in the thyroid follicular cells. TSH binding to the cell membrane G protein-coupled receptor activates the cAMP and phospholipase C signalling pathways, which in turn upregulates the process of iodine uptake and organification, thyroglobulin synthesis, iodotyrosine coupling and iodothyronine (T3, T4) secretion, leading to a short-term response in thyroid hormone production. […] In the long-term, TSH also stimulates proliferation of follicular cells to increase the functional mass of thyroid gland. Clinically, TSH stimulation results in enlargement of thyroid gland, increased radio-iodine uptake and increased T4 and T3 levels.

• #22 A Review of the Pathogenesis and Management of Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/46424

  Nodule formation is postulated to be the result of both an inherent and acquired heterogeneity in proliferative and functional upregulation of the follicular cells. The thyroid follicular cells are inherently heterogeneous with regard to thyroid hormone production and proliferation in response to TSH stimulation, such that under intermediate level of stimulation, a subpopulation of follicular cells outgrows other cells and expand into macroscopic nodules. […] On the other hand, follicular cells acquiring activating somatic mutations in the cell proliferation pathways can expand clonally to form a nodule. About 60 70% of nodules form by the later mechanism and are monoclonal in origin. Somatic mutations leading to constitutive activation of TSH receptors are found in about 60% of autonomously functioning nodules.

• #23 A Review of the Pathogenesis and Management of Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/46424

  Nodule formation is postulated to be the result of both an inherent and acquired heterogeneity in proliferative and functional upregulation of the follicular cells. The thyroid follicular cells are inherently heterogeneous with regard to thyroid hormone production and proliferation in response to TSH stimulation, such that under intermediate level of stimulation, a subpopulation of follicular cells outgrows other cells and expand into macroscopic nodules. […] On the other hand, follicular cells acquiring activating somatic mutations in the cell proliferation pathways can expand clonally to form a nodule. About 60 70% of nodules form by the later mechanism and are monoclonal in origin. Somatic mutations leading to constitutive activation of TSH receptors are found in about 60% of autonomously functioning nodules.

• #24 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  Toxic nodular goiter (TNG) represents a spectrum of disease ranging from a single hyperfunctioning nodule (toxic adenoma) within a multinodular thyroid to a gland with multiple areas of hyperfunction. The natural history of a multinodular goiter involves variable growth of individual nodules; this may progress to hemorrhage and degeneration, followed by healing and fibrosis. Calcification may be found in areas of previous hemorrhage. […] Some nodules may develop autonomous function. Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin, or thyroid-stimulating hormone (TSH), receptor in 20-80% of toxic adenomas and some nodules of multinodular goiters. Autonomously functioning nodules may become toxic in 10% of patients. Hyperthyroidism predominantly occurs when single nodules are larger than 2.5 cm in diameter. Signs and symptoms of TNG are similar to those of other types of hyperthyroidism.

• #25 Multinodular Goiter: Pathogenesis and Management | Oncohema Key

  https://oncohemakey.com/multinodular-goiter-pathogenesis-and-management/

  However, most patients with goiter have normal levels of TSH, and TSH suppression by the administration of levothyroxine may not stop thyroid growth. […] Genetic factors also play a significant role in the pathogenesis of nodular goiter as shown by a study that evaluated twins, and demonstrated that genetic factors accounted for 71% (61% to 78%) of the individual differences in thyroid volume. […] The occurrence of familial cases of nodular goiter, at early ages in many cases, strengthens the hypothesis that genetic factors are involved in the pathogenesis of goiter.

• #26 Multinodular Goiter – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK285569/

  Genetic heterogeneity of normal follicular cells and acquisition of new inheritable qualities by replicating epithelial cells. […] Newly generated cells may acquire qualities not previously present in mother cells. These qualities could subsequently be passed on to further generations of cells. […] In contrast to sporadic goiters, caused by spontaneous recessive genomic variation, most cases of familial goiter present an autosomal dominant pattern of inheritance, indicating predominant genetic defects. […] Defects in genes that play an important role in thyroid physiology and thyroid hormone synthesis could predispose to the development of goiter, especially in case of borderline or overt iodine deficiency. […] The secondary factors discussed below stimulate thyroid cell growth and/or function and, because of differences in cellular responsiveness that are presumed to exist, aggravate the expression of heterogeneity which leads to further growth and focal autonomic function of the thyroid gland.

• #27 Multinodular Goiter – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK285569/

  Genetic heterogeneity of normal follicular cells and acquisition of new inheritable qualities by replicating epithelial cells. […] Newly generated cells may acquire qualities not previously present in mother cells. These qualities could subsequently be passed on to further generations of cells. […] In contrast to sporadic goiters, caused by spontaneous recessive genomic variation, most cases of familial goiter present an autosomal dominant pattern of inheritance, indicating predominant genetic defects. […] Defects in genes that play an important role in thyroid physiology and thyroid hormone synthesis could predispose to the development of goiter, especially in case of borderline or overt iodine deficiency. […] The secondary factors discussed below stimulate thyroid cell growth and/or function and, because of differences in cellular responsiveness that are presumed to exist, aggravate the expression of heterogeneity which leads to further growth and focal autonomic function of the thyroid gland.

• #28 Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/70705

  Chronic stimulation of follicular cells primarily due to TSH leads to follicular hyperplasia, which usually then enters a resting phase leading to the formation of colloid goiter. […] The role of genetic factors especially in nontoxic MNG is not clear, but some role has been suggested by twin studies, family history, female preponderance, etc. […] Certain mutations like those affecting the activation of camp cascade (e.g., TSH-r mutations) which stimulates growth and function mutation in genes encoding thyroglobulin (Tg), thyroid peroxidase (TPO), dual oxidase 2 (THOX2), the sodium-iodide symporter gene (SLC5A5), Pendred syndrome gene (SLC26A4), the TSH receptor gene (TSHR gene), the iodotyrosine deiodinase (DEHAL 1), and the thyroid oxidase 2 gene (THOX2) have been found to be responsible in certain cases for the formation of nodules in a patient with MNG. […] Environmental factors have also been incriminated in causation of MNG possibly by aggravating the expression of heterogeneity causing the thyroid to grow and perhaps leading to its autonomy.

• #29 Multinodular Goiter | IntechOpen

  https://www.intechopen.com/chapters/70705

  Chronic stimulation of follicular cells primarily due to TSH leads to follicular hyperplasia, which usually then enters a resting phase leading to the formation of colloid goiter. […] The role of genetic factors especially in nontoxic MNG is not clear, but some role has been suggested by twin studies, family history, female preponderance, etc. […] Certain mutations like those affecting the activation of camp cascade (e.g., TSH-r mutations) which stimulates growth and function mutation in genes encoding thyroglobulin (Tg), thyroid peroxidase (TPO), dual oxidase 2 (THOX2), the sodium-iodide symporter gene (SLC5A5), Pendred syndrome gene (SLC26A4), the TSH receptor gene (TSHR gene), the iodotyrosine deiodinase (DEHAL 1), and the thyroid oxidase 2 gene (THOX2) have been found to be responsible in certain cases for the formation of nodules in a patient with MNG. […] Environmental factors have also been incriminated in causation of MNG possibly by aggravating the expression of heterogeneity causing the thyroid to grow and perhaps leading to its autonomy.

• #30 Goitre Causes, investigation and management

  https://www.racgp.org.au/afp/2012/august/goitre

  Goitre refers to an enlarged thyroid. Common causes of goitre include autoimmune disease, thyroid nodules and iodine deficiency. […] When diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism, it is referred to as a diffuse nontoxic goitre. […] The prevalence of goitre, diffuse and nodular, is dependent on the status of iodine intake of the population. […] Smoking is also known to be goitrogenic, with cigarette smoke containing goitrogens including thiocyanates. […] Iodine deficiency has re-emerged in Australia over recent decades. […] Nodular goitre is most often detected simply as a mass in the neck, but an enlarging gland may also produce pressure symptoms on the trachea and the oesophagus. […] Patients with goitre or thyroid nodules should have a serum thyroid stimulating hormone (TSH) to determine the current functional status of the thyroid.

• #31 Goiter in Animals – Endocrine System – Merck Veterinary Manual

  https://www.merckvetmanual.com/endocrine-system/the-thyroid-gland/goiter-in-animals

  A goiter is an enlarged thyroid gland. […] Common causes of goiter include the following: iodine deficiency or excess, ingestion of goitrogenic plants, hereditary factors, congenital hypothyroidism and dysmaturity syndrome. […] With lower concentrations of circulating thyroid hormones, the pituitary secretes more thyroid-stimulating hormone (TSH), which stimulates hyperplasia of the thyroid gland and subsequent development of a goiter. […] All goitrogenic substances interfere with the production of thyroid hormones. As in cases of iodine deficiency, the pituitary gland responds to lower concentrations of circulating thyroid hormones by increasing its secretion of TSH, leading to thyroid gland enlargement. […] Familial dyshormonogenetic goiter has been reported in sheep, cattle, goats, and pigs. It appears to be inherited as an autosomal recessive trait. The cause is a genetic enzyme defect in the biosynthesis of thyroid hormones. As with iodine deficiency, in this condition decreased production of thyroid hormones leads to increased concentrations of TSH and subsequent goiter.

• #32 Goiter defination ,pathogenesis,classification.pptx

  https://www.slideshare.net/slideshow/goiter-defination-pathogenesisclassificationpptx-254564905/254564905

  Stimulation of the thyroid gland by TSH, Inappropriate secretion from the anterior pituitary a microadenoma In response to a chronically low level of circulating thyroid hormones. 1. Dietary deficiency of iodine, 2 Goitrogens in food. 3. Defective hormone synthesis (Dyshormonogenesis) sporadic goitres. […] Somewhat surprisingly TSH levels are normal in simple goiter.

• #33 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  Toxic nodular goiter (TNG) represents a spectrum of disease ranging from a single hyperfunctioning nodule (toxic adenoma) within a multinodular thyroid to a gland with multiple areas of hyperfunction. The natural history of a multinodular goiter involves variable growth of individual nodules; this may progress to hemorrhage and degeneration, followed by healing and fibrosis. Calcification may be found in areas of previous hemorrhage. […] Some nodules may develop autonomous function. Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin, or thyroid-stimulating hormone (TSH), receptor in 20-80% of toxic adenomas and some nodules of multinodular goiters. Autonomously functioning nodules may become toxic in 10% of patients. Hyperthyroidism predominantly occurs when single nodules are larger than 2.5 cm in diameter. Signs and symptoms of TNG are similar to those of other types of hyperthyroidism.

• #34 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  Toxic nodular goiter (TNG) represents a spectrum of disease ranging from a single hyperfunctioning nodule (toxic adenoma) within a multinodular thyroid to a gland with multiple areas of hyperfunction. The natural history of a multinodular goiter involves variable growth of individual nodules; this may progress to hemorrhage and degeneration, followed by healing and fibrosis. Calcification may be found in areas of previous hemorrhage. […] Some nodules may develop autonomous function. Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin, or thyroid-stimulating hormone (TSH), receptor in 20-80% of toxic adenomas and some nodules of multinodular goiters. Autonomously functioning nodules may become toxic in 10% of patients. Hyperthyroidism predominantly occurs when single nodules are larger than 2.5 cm in diameter. Signs and symptoms of TNG are similar to those of other types of hyperthyroidism.

• #35 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  Functional autonomy of the thyroid gland appears to be related to iodine deficiency. Various mechanisms have been implicated, but the molecular pathogenesis is poorly understood. […] The sequence of events leading to toxic multinodular goiter is as follows: Iodine deficiency leads to low levels of T4; this induces thyroid cell hyperplasia to compensate for the low levels of T4. Increased thyroid cell replication predisposes single cells to somatic mutations of the TSH receptor. Constitutive activation of the TSH receptor may generate autocrine factors that promote further growth, resulting in clonal proliferation. Cell clones then produce multiple nodules. […] Somatic mutations of the TSH receptors and G protein confer constitutive activation to the cyclic adenosine monophosphate (cAMP) cascade of the inositol phosphate pathways. These mutations may be responsible for functional autonomy of the thyroid in 20-80% of cases.

• #36 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  Functional autonomy of the thyroid gland appears to be related to iodine deficiency. Various mechanisms have been implicated, but the molecular pathogenesis is poorly understood. […] The sequence of events leading to toxic multinodular goiter is as follows: Iodine deficiency leads to low levels of T4; this induces thyroid cell hyperplasia to compensate for the low levels of T4. Increased thyroid cell replication predisposes single cells to somatic mutations of the TSH receptor. Constitutive activation of the TSH receptor may generate autocrine factors that promote further growth, resulting in clonal proliferation. Cell clones then produce multiple nodules. […] Somatic mutations of the TSH receptors and G protein confer constitutive activation to the cyclic adenosine monophosphate (cAMP) cascade of the inositol phosphate pathways. These mutations may be responsible for functional autonomy of the thyroid in 20-80% of cases.

• #37 Toxic multinodular goitre – Wikipedia

  https://en.wikipedia.org/wiki/Toxic_multinodular_goitre

  Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism. […] It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH). […] Sequence of events: Iodine deficiency leading to decreased T4 production. Induction of thyroid cell hyperplasia due to low levels of T4. This accounts for the multinodular goitre appearance. Increased replication predisposes to a risk of mutation in the TSH receptor. If the mutated TSH receptor is constitutively active, it would then become 'toxic’ and produces excess T3/T4 leading to hyperthyroidism. […] Toxic multinodular goiter can be treated with antithyroid medications such as propylthiouracil or methimazole, radioactive iodine, or with surgery.

• #38 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  Functional autonomy of the thyroid gland appears to be related to iodine deficiency. Various mechanisms have been implicated, but the molecular pathogenesis is poorly understood. […] The sequence of events leading to toxic multinodular goiter is as follows: Iodine deficiency leads to low levels of T4; this induces thyroid cell hyperplasia to compensate for the low levels of T4. Increased thyroid cell replication predisposes single cells to somatic mutations of the TSH receptor. Constitutive activation of the TSH receptor may generate autocrine factors that promote further growth, resulting in clonal proliferation. Cell clones then produce multiple nodules. […] Somatic mutations of the TSH receptors and G protein confer constitutive activation to the cyclic adenosine monophosphate (cAMP) cascade of the inositol phosphate pathways. These mutations may be responsible for functional autonomy of the thyroid in 20-80% of cases.

• #39 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  These mutations are found in autonomously functioning thyroid nodules, solitary and within a multinodular gland. Nonfunctioning thyroid nodules within the same gland lack these mutations. […] The reported frequency of these mutations varies widely, ranging from 10-80%. Higher incidence is reported in patients with iodine deficiency. […] In addition to somatic mutations, polymorphisms of the TSH receptor have been studied in patients with toxic nodular goiter (TNG); notably, polymorphisms involving the carboxyl-terminal tail of the human TSH receptor have been found in nodular and genomic deoxyribonucleic acid (DNA). […] Unlike the somatic mutations found in autonomously functioning nodules, these mutations have also been found in other cell lines, indicating a germline mutation. One of these, D727E, was present with greater frequency in patients with TNG than in healthy individuals; this suggests that this polymorphism may be associated with the disease.

• #40

  https://link.springer.com/article/10.1007/s00423-011-0788-5

  Familial clustering of goiters mostly with an autosomal dominant pattern of inheritance has repeatedly been reported. […] Moreover, other environmental and etiologic factors are likely to be involved in the development of euthyroid goiter. Therefore, a multifactorial etiology based on complex interactions of both genetic predisposition and the individuals environment is likely. […] The nodular process is triggered by the oxidative nature of thyroid hormone synthesis or additional oxidative stress caused by iodine deficiency or smoking. If the antioxidant defense is not effective, this oxidative stress will cause DNA damage followed by an increase of the spontaneous mutation rate which is a substrate for tumorogenesis. […] Therefore, the hallmark of thyroid physiology H2O2 production during hormone synthesis is very likely the ultimate cause for the frequent mutagenesis in the thyroid gland. Because iodine deficiency increases the oxidative burden, DNA damage and mutagenesis could provide the basis for the frequent nodular transformation of endemic goiters.

• #41

  https://link.springer.com/article/10.1007/s00423-011-0788-5

  Familial clustering of goiters mostly with an autosomal dominant pattern of inheritance has repeatedly been reported. […] Moreover, other environmental and etiologic factors are likely to be involved in the development of euthyroid goiter. Therefore, a multifactorial etiology based on complex interactions of both genetic predisposition and the individuals environment is likely. […] The nodular process is triggered by the oxidative nature of thyroid hormone synthesis or additional oxidative stress caused by iodine deficiency or smoking. If the antioxidant defense is not effective, this oxidative stress will cause DNA damage followed by an increase of the spontaneous mutation rate which is a substrate for tumorogenesis. […] Therefore, the hallmark of thyroid physiology H2O2 production during hormone synthesis is very likely the ultimate cause for the frequent mutagenesis in the thyroid gland. Because iodine deficiency increases the oxidative burden, DNA damage and mutagenesis could provide the basis for the frequent nodular transformation of endemic goiters.

• #42 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  The presence of the heterozygous state for the D727E variant of the human TSH receptor alone is not sufficient for the development of the TNG. Approximately 10% of healthy individuals have this polymorphism. […] Possible mediators in growth include the following: Endothelin-1 (ET-1) production is increased in rat thyroid glands that have undergone hyperplasia; this suggests that ET-1 production may be involved in thyroid gland growth and vascularity. In contrast to normal thyroid tissue and papillary thyroid cancer, thyroid tissue in patients with TNG shows markedly positive staining of the stroma but absent staining of the follicular cells. The significance of this finding is unclear, but ET-1 is, in addition to being a vasoconstrictor, a mitogen for vascular endothelium, smooth muscle cells, and thyroid follicular cells.

• #43 Toxic Nodular Goiter: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/120497-overview

  In vitro systems have shown stimulation of thyroid follicular cell proliferation with insulinlike growth factor-1, epidermal growth factor, and fibroblast growth factor. Reduced concentrations of transforming growth factor- 1 or resistance to transforming growth factor- have also been associated with follicular cell growth. The role of these multiple factors in the growth and secretory function of TNG needs further investigation.

• #44

  https://www.jci.org/articles/view/113955

  The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. […] Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. […] The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves’ disease and normal thyroid tissue. […] These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. […] Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter.

• #45

  https://www.jci.org/articles/view/112199

  Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from „cold” and „hot” regions of 20 goiters transplanted onto nude mice. […] Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. […] Intercellular differences of iodinating activity were not abolished by TSH. […] Autonomy of growth and autonomy of function are independent traits of epithelial cells. […] To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.

• #46

  https://www.jci.org/articles/view/112199

  Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from „cold” and „hot” regions of 20 goiters transplanted onto nude mice. […] Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. […] Intercellular differences of iodinating activity were not abolished by TSH. […] Autonomy of growth and autonomy of function are independent traits of epithelial cells. […] To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.

• #47 Goiter – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562161/

  Several pathogenic mechanisms can cause goiter. It can be caused by iodine deficiency, which is often seen in countries that do not have a public health intervention to prevent iodine deficiency. […] Inflammatory disorders of the thyroid gland such as autoimmune thyroiditis, postpartum thyroiditis, silent thyroiditis, radiation thyroiditis, subacute thyroiditis, and suppurative thyroiditis can cause thyroid enlargement, hence goiter. […] Enlargement of thyroid, i.e. goiter is an adaptive reaction of thyroid follicular cells to any process that blocks thyroid hormone production. The most common cause of goiter is iodine deficiency. […] Goiters have various morphological, hormonal, and clinical presentations and not all causes of goiter can be attributed to iodine deficiency. Genetic, demographic, and environmental factors are also responsible for the development of goiter.

• #48 Multinodular Goiter – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK285569/

  Most goiters become nodular with time. […] Epidemiologic studies, animal models and molecular/genetic data outline a general theory of nodular transformation. […] The hypothesis that the development of thyroid autonomy is due to a gradual increase in the numbers of cells having relatively autonomous thyroid hormone synthesis is supported by the 27% prevalence of impaired TSH responses to TRH in patients with nodular goiter as opposed to such responses in only 1 of 15 patients with diffuse goiter. […] Thus, there may be several etiologic factors in simple and nodular goiter, and some of these factors may act synergistically. The end result is a collection of heterogeneously functioning thyroid follicles, some of which may be autonomous and produce sufficient amounts of thyroid hormone to cause hyperthyroidism.

• #49 Multinodular Goiter: Pathogenesis and Management | Oncohema Key

  https://oncohemakey.com/multinodular-goiter-pathogenesis-and-management/

  Multinodular goiter (MNG) and diffuse goiter are defined as the enlargement of the thyroid gland, in the absence of autoimmune thyroid disease, malignancy, or inflammation. […] Both genetic and environmental factors are involved in the goitrogenic process, but iodine deficiency is the most important risk factor. […] The pathogenesis of nontoxic diffuse and nodular goiter is determined by exogenous and endogenous factors. Worldwide, iodine deficiency is the most important factor that increases the risk for the development of endemic and sporadic goiter, and their prevalence are inversely proportional to the iodine intake. […] There is a direct correlation between the degree of iodine deficiency and the prevalence and size of the goiter, which is a physiologic adaptation to the lack of iodine.

• #50 Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter

  https://ouci.dntb.gov.ua/en/works/42zDrnX4/

  The purpose of this review is to summarize current knowledge of the etiology of euthyroid and toxic multinodular goiter (MNG) with respect to the epidemiology, clinical characteristics, and molecular pathology. […] In reconstructing the line of events from early thyroid hyperplasia to MNG we will argue the predominant neoplastic character of nodular structures, the nature of known somatic mutations, and the importance of mutagenesis. […] Furthermore, we outline direct and indirect consequences of these somatic mutations for thyroid pathophysiology and summarize information concerning a possible genetic background of euthyroid goiter. […] Finally, we discuss uncertainties and open questions in differential diagnosis and therapy of euthyroid and toxic MNG.

• #51 Pathogenesis of nodular goiter and its implications for surgical management

  https://inis.iaea.org/records/gf63q-h5623

  Despite sufficient iodine supply, goiter continues to be of considerable surgical significance in formerly endemic countries. […] It now appears that iodine deficiency and increased thyrotropin stimulation are not the only causes of goiter. […] Thus, our pathogenetic concept of goiter formation is based on three mainstays: (1) goiter heterogeneity, (2) autonomy of growth and function, and (3) dissociation of growth and function in human goiter tissue. […] Thus, the surgeon dealing with goiter ought to remove all pathologically altered tissue, i.e., nodular tissue, irrespective of its appearance on scintiscans.

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