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. In this instance, the terminology is an endemic goiter. 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. In countries that use iodized salt and in others where iodine deficiency is not a problem, Hashimoto thyroiditis is an important cause of goiter. However, iodine deficiency still remains the most common cause worldwide. 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. Other causes include Graves disease, inborn errors of thyroid hormone synthesis, congenital hypothyroidism, inflammatory thyroid diseases like postpartum thyroiditis, infiltrative diseases of thyroid like sarcoidosis, and amyloidosis, TSH secreting pituitary adenomas, and others.

• #2 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.

• #3 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.

• #4 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. Occasionally it may enlarge rapidly and gives the impression of subacute thyroiditis. Elevated TSH levels due to hypothyroidism may also contribute to goiter in autoimmune thyroid disease. As Hashimotos thyroiditis progresses and follicular cells are destroyed by inflammation and fibrosis component increases, the thyroid volume decreases and the gland becomes atrophic with chronic atrophic thyroiditis. There are several variations in the clinical course and heterogeneity in presentation for Hashimotos thyroiditis and also other autoimmune thyroid disorders. 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. 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. Eventually, the thyroid gland becomes enlarged leading to the development of a goiter.

• #5 Goiter pathophysiology – wikidoc

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

  When the thyrotrophin releasing hormone-thyroid stimulating hormone axis (TRH-TSH thyroid hormone axis) is interfered, it results in structural and functional changes in 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 occurs continuously, it leads to goiter. […] Goiters may occur as a result of either hypothyroidism, hyperthyroidism, or even with normal levels of thyroid hormone. […] When the thyroid gland cannot secrete enough thyroid hormone to cater to the metabolic requirements, it may lead to simple goiter (smooth enlargement). […] In order to compensate for inadequate hormone synthesis, the thyroid gland enlarges, this type of compensation overcomes mild to moderate hormonal impairment.

• #6 Goitre – Wikipedia

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

  A goitre 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. […] Hashimoto’s thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed. […] Graves’ disease is characterized by autoantibodies that activate the TSH-receptor, leading to hyperthyroidism.

• #7 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.

• #7 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.

• #8 Colloid Nodular Goiter – Endocrine Surgery | UCLA Health

  https://www.uclahealth.org/medical-services/surgery/endocrine-surgery/patient-resources/patient-education/endocrine-surgery-encyclopedia/colloid-nodular-goiter

  Colloid nodular goiter occurs when the thyroid gland is unable to meet the metabolic demands of the body with sufficient hormone production. The thyroid gland compensates by enlarging, which usually overcomes mild deficiencies of thyroid hormone. […] If the thyroid gland is then re-exposed to iodine, the nodules may produce thyroid hormone independently. Occasionally, the nodules may produce too much thyroid hormone, causing thyrotoxicosis. This is called a toxic nodular goiter. […] Colloid nodular goiters are also known as endemic goiters and are usually caused by inadequate iodine in diet. […] A simple goiter may progress to a toxic nodular goiter. […] Thyrotoxicosis may occur spontaneously with iodine re-exposure.

• #9 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.

• #10 Goiter – StatPearls – NCBI Bookshelf

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

  goiter is common in some families. In iodine deficiency areas, after iodine is supplemented, the goiter incidence does not drop to zero and there is the persistence of goiter in some families. The concordance of goiter is higher in monozygotic twins than dizygotic. Mutations in sodium iodide symporter, thyroid peroxidase, dual oxidase 2, pendrin, and TSH receptor gene have been identified responsible for the development of goiter. […] diffuse nontoxic goiter is considered to be the precursor of euthyroid thyroid nodules and nontoxic multinodular goiter. So the pathophysiology of diffuse nontoxic goiter also applies to nodular goiter. In addition, the following mechanisms can be considered: […] accidental or medical radiation, by external ionizing radiation or radioactive iodine, causes thyroid abnormalities. Individuals exposed to radiation under the age of 20 years have an increase in the incidence of thyroid nodules in early years and papillary thyroid cancer as they age.

• #11

  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.

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

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

  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. […] TSH is the most important growth factor involved in the pathogenesis of nodular goiter. […] 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% 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.

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

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

  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. […] The reported frequency of these mutations varies widely, ranging from 10-80%. Higher incidence is reported in patients with iodine deficiency. […] 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.

• #14 Multinodular goiter | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/multinodular-goiter-1?lang=us

  Multinodular goiters develop from simple goiters as a result of repeated instances of stimulation and involution. […] Most of the nodules are hyperplastic or adenomatous with varying degree of cystic/liquefactive degeneration. […] A nodule in multinodular goiter may harbor malignancy. A family history of malignancy and prior neck radiation exposure are known risk factors.

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

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

  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.

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

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

  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. […] 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.

• #16 Vitamin D status in Egyptian euthyroid multinodular non-toxic goiter patients and its correlation with TSH levels | Endocrinología y Nutrición (English Edition)

  https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-vitamin-d-status-in-egyptian-S2173509316300770

  Although the prevalence of MNG is widespread throughout the world, its pathogenesis is poorly understood, and the complex interactions of both genetic predisposition and the individuals environment are likely. […] It is clear now that although iodine deficiency has a pivotal role in pathogenesis of goiter and nodule formation, it does not fully explain the pathogenesis of MNG. […] 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 stimulates pituitary secretion of thyroid stimulating hormone (TSH).

• #17 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. […] 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.

• #18 Goiter – StatPearls – NCBI Bookshelf

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

  up to 70% of toxic adenomas harbor a somatic point mutation in the TSH receptor gene. These mutations cause constitutive activation of the TSH receptor without TSH stimulation. A minority of toxic adenomas has a mutation in the G protein genes. EZH1 gene mutation has been found in toxic adenomas that have a TSH receptor activating mutation suggesting a second hit. […] nontoxic multinodular goiter and/or single toxic adenomas are considered as precursors of toxic multinodular goiter (Plummers Disease). When a nodule or several nodules in nontoxic multinodular goiter gain autonomy, they secrete excess thyroid hormones and lower TSH levels causing the development of toxic multinodular goiter. During the transition from nontoxic to toxic goiter, pathophysiological and morphological alterations occur. Histology of toxic multinodular goiter shows nodules well demarcated from the rest of the thyroid gland. Some of these nodules may be hot whereas some of these nodules may be cold or somewhere in between (cool, warm, or normoactive) with the remaining of the non-nodular thyroid tissue either partially or completely suppressed. Microscopically nodules have large follicles with epithelial hyperplasia. The non-nodular tissue is not hyperplastic and may contain areas of degeneration and is functionally less active or inactive as seen in the nuclear medicine radioiodine scan.

• #19 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.

• #20 Toxic multinodular goitre

  http://med.iiab.me/kiwix/wikipedia_en_medicine_2019-12/A/Toxic_multinodular_goitre

  Toxic multinodular goiter 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.

• #21 Simple goiter: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001178.htm

  A simple goiter is an enlargement of the thyroid gland. It is usually not a tumor or cancer. […] Iodine deficiency is the most common cause of goiter. The body needs iodine to produce thyroid hormone. If you do not have enough iodine in your diet, the thyroid gets larger to try and capture all the iodine it can, so it can make the right amount of thyroid hormone. So, a goiter can be a sign the thyroid is not able to make enough thyroid hormone. […] Other causes of goiter include: The body’s immune system attacking the thyroid gland (autoimmune problem), Certain medicines (lithium, amiodarone), Infections (rare), Cigarette smoking, Eating very large amounts of certain foods (soy, peanuts, or vegetables in the broccoli and cabbage family), Toxic nodular goiter, an enlarged thyroid gland that has a small growth or many growths called nodules, which produce too much thyroid hormone.

• #22 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. […] Patients with goitre may be asymptomatic, or may present with compressive symptoms such as cough or dysphagia. Goitre may also present with symptoms due to associated hypothyroidism or hyperthyroidism. […] When diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism, it is referred to as a diffuse nontoxic goitre. This is sometimes called 'simple goitre’ because of the absence of nodules, or 'colloid goitre’ because of the presence of uniform follicles that are filled with colloid. […] 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. Smoking may also exacerbate autoimmune thyroid disease (and possibly autoimmunity in general).

• #23 Multinodular Goiter – Endocrinology Advisor

  https://www.endocrinologyadvisor.com/ddi/multinodular-goiter/

  A goiter is an enlargement of the thyroid gland. A multinodular goiter occurs when several abnormal growths of thyroid cells are present. It may occur as a result of hyperthyroidism or hypothyroidism, and factors contributing to the development of multinodular goiter include iodine deficiency and genetic or environmental causes. […] Goiter may occur as a result of hyperthyroidism or hypothyroidism, and factors contributing to the development of multinodular goiter include iodine deficiency and genetic or environmental causes. […] Because goiter has been diagnosed in people who reside in areas without iodine deficiency, other factors may contribute to its development. Some of these include other environmental causes, gene abnormalities, and demographic causes. Environmental contributors that may interfere with the endocrine system and contribute to the development of goiter include exposure to the following: Perchlorate, Thiocyanate, Phthalates, Nitrates, Isoflavones, Organochlorines.

• #24 Multinodular Goiter – Endotext – NCBI Bookshelf

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

  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. […] Most goiters become nodular with time. […] It is known that thyroid hormone synthesis goes along with increased H2O2 production and free radical formation with may damage genomic DNA and cause mutations. […] 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.

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

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

  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 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.

• #26

  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. […] Proliferation and function of follicular cells were assessed in whole follicles reconstructed from autoradiographs of serial sections. […] Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. […] Functional autonomy widely varied among the follicles, but even more so among individual cells. […] Hot grafts differed from cold ones only by a comparatively larger fraction of autonomous cells. […] Intercellular differences of iodinating activity were not abolished by TSH. […] Grafts faithfully reproduced the individual growth pattern of the original tissue.

• #27

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

  Between 0.5% and 7% of all follicular cells replicated despite suppression of TSH. […] Up to 70% of these cells were clustered, forming scattered foci of autonomously growing tissue. […] Other cells only started replicating after long-term TSH stimulation. […] Thus, goiters contained subsets of cells with high and others with low growth response. […] Autonomy of growth and autonomy of function are independent traits of epithelial cells. […] Epithelial cells have their individual growth pattern, replication rate, and functional capacity. […] These traits are passed on from a mother cell to its progeny during follicle neogenesis. […] To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.

• #28 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).

• #29 Toxic multinodular goiter pathophysiology – wikidoc

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

  The progression to Toxic multinodular goiter usually involves the somatic gain-of-function mutations in the TSH receptor. […] More than 30 different activating mutations causing nonautoimmune hyperthyroidism have been found which includes mutation in toxic nodule and multi nodular toxic goiter. […] Activating mutations in the TSH-R genes may lead to increase of basal and TSH-induced activation of cAMP or inositol phosphate (IP) cascades which keep TSH-R in opened unliganded or hormone-activated state. it is called somatic gain-of-function mutations. […] Studies have shown that the solitary toxic nodule may have same pathogenesis in multi nodular toxic goiter. […] Different nodules in multi-nodular goiter may have many hyperfunctioning nodules with different gain-in -function mutations which may be due different clonal origin. […] In patients with Toxic multinodular goiter TSH is decreased and T3 and T4 is found in increased levels in serum.

• #30 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.

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