Materiały źródłowe

• #1 Pathogenesis of Graves’ disease – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-graves-disease

  Pathogenesis of Graves’ disease is a syndrome that may consist of hyperthyroidism, goiter, thyroid eye disease (TED; Graves’ orbitopathy), and occasionally a dermopathy referred to as pretibial or localized myxedema (PTM). […] Nevertheless, hyperthyroidism is the most common feature of Graves’ disease, affecting nearly all patients, and is caused by autoantibodies to the thyrotropin receptor (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter). […] This topic will review the immune pathogenesis of Graves’ thyroid disease, with emphasis on the role of B and T cells in the production of the TRAb that are responsible for the thyroid stimulation and growth. […] In Graves’ disease, the main autoantigen is the thyroid-stimulating hormone (TSH, thyrotropin) receptor (TSHR), which is expressed primarily in the thyroid but also in adipocytes, fibroblasts, bone cells, brain tanycytes and a variety of additional cells.

• #2 Pathogenesis of Graves’ disease – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-graves-disease/print

  Graves’ disease is a syndrome that may consist of hyperthyroidism, goiter, thyroid eye disease (TED; Graves’ orbitopathy), and occasionally a dermopathy referred to as pretibial or localized myxedema (PTM). […] Nevertheless, hyperthyroidism is the most common feature of Graves’ disease, affecting nearly all patients, and is caused by autoantibodies to the thyrotropin receptor (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter). […] This topic will review the immune pathogenesis of Graves’ thyroid disease, with emphasis on the role of B and T cells in the production of the TRAb that are responsible for the thyroid stimulation and growth. […] In Graves’ disease, the main autoantigen is the thyroid-stimulating hormone (TSH, thyrotropin) receptor (TSHR), which is expressed primarily in the thyroid but also in adipocytes, fibroblasts, bone cells, brain tanycytes and a variety of additional cells. […] However, factors that contribute to TSHR presentation as a target for the immune system in humans are not well understood but are considered to be primarily factors that build on a state of enhanced genetic susceptibility combined with a failure of immune tolerance.

• #2 Graves Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448195/

  Graves’ disease is an autoimmune disease which primarily affects the thyroid gland. It may also affect multiple other organs including eyes and skin. It is the most common cause of hyperthyroidism. […] Graves’ disease is caused by thyroid stimulating immunoglobulin (TSI), also known as thyroid stimulating antibody (TSAb). B lymphocytes primarily synthesize Thyroid stimulating immunoglobulin within the thyroid cells, but it can also be synthesized in lymph nodes and bone marrow. B lymphocytes are stimulated by T lymphocytes which get sensitized by antigen in the thyroid gland. Thyroid stimulating immunoglobulin binds with thyroid-stimulating hormone (TSH) receptor on the thyroid cell membrane and stimulates the action of the thyroid-stimulating hormone. It stimulates both, thyroid hormone synthesis and thyroid gland growth, causing hyperthyroidism and thyromegaly.

• #3 Graves Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/120619-overview

  In Graves disease, B and T lymphocyte-mediated autoimmunity are known to be directed at 4 well-known thyroid antigens: thyroglobulin, thyroid peroxidase, sodium-iodide symporter and the TSH receptor. However, the TSH receptor itself is the primary autoantigen of Graves disease and is responsible for the manifestation of hyperthyroidism. […] The thyroid gland is under continuous stimulation by circulating autoantibodies against the TSH receptor, and pituitary TSH secretion is suppressed because of the increased production of thyroid hormones. […] The stimulating activity of TSH-receptor antibodies is found mostly in the immunoglobulin G1 subclass. These thyroid-stimulating antibodies cause release of thyroid hormone and thyroglobulin that is mediated by 3,’5′-cyclic adenosine monophosphate (cyclic AMP), and they also stimulate iodine uptake, protein synthesis, and thyroid gland growth.

• #4 Graves’ Disease: Pathophysiology, Genetics and Management | IntechOpen

  https://www.intechopen.com/chapters/76867

  By circulating autoantibodies against the thyrotropin receptor, the thyroid gland is under continuous stimulation, and because of the increased production of thyroid hormones pituitary thyrotropin secretion is suppressed. […] The release of thyroid hormone and thyroglobulin that is mediated via 3,’5-cyclic adenosine monophosphate (cyclic AMP) are caused by these thyroid-stimulating antibodies, and they also stimulate iodine uptake, protein synthesis, and thyroid gland growth. […] In addition to autoantigens, the cells of thyroid produce specific immune mediators such as cytokines and Fas which are involved in various immune process including complement legislation and T cell adhesion. […] CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 are several autoimmune thyroid disease susceptibility genes that have been identified.

• #4 Graves’ Disease: Pathophysiology, Genetics and Management | IntechOpen

  https://www.intechopen.com/chapters/76867

  Graves disease is an autoimmune disorder in which hyperthyroidism (over active thyroid) is caused by the autoantibodies against the TSH receptor. […] The autoimmune basis of the GD results from complex interactions between different factors which include genetic, endogenous and environmental factors, and this is compulsory for current understanding of this disease. […] The circulating antibodies (IgG) that binds and activates the G-protein coupled thyrotropin receptor leads to hyperthyroidism in this disease. […] In GD, four standard thyroid antigens: thyroglobulin, thyroid peroxidase, sodium-iodide symporter and the thyrotropin receptor are recognized to direct B and T lymphocyte-mediated autoimmunity. However, the primary auto antigen of GD is the thyrotropin receptor itself and is responsible for the manifestation of hyperthyroidism.

• #5 Hyperthyroidism – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/thyroid-disorders/hyperthyroidism

  Graves disease is caused by an autoantibody (TSI) against the thyroid receptor for thyroid-stimulating hormone (TSH); unlike most autoantibodies, which are inhibitory, this autoantibody is stimulatory, thus causing continuous synthesis and secretion of excess T4 and T3. […] The pathogenesis of infiltrative ophthalmopathy (responsible for the exophthalmos in Graves disease) is poorly understood but may result from immunoglobulins directed to the TSH receptors in the orbital fibroblasts and fat that result in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans.

• #6 Regulatory T Cells in the Pathogenesis of Graves’ Disease

  https://www.mdpi.com/1422-0067/24/22/16432

  Failure of negative regulation of inflammation plays a pivotal role in GD pathogenesis. The thyroid gland of GD patients has characteristic lymphocytic infiltration of T and B lymphocytes that are autoreactive to the TSHR after evading thymic and peripheral deletion. Abnormal HLA-DR expression allows thyroid cells to directly present autoantigens to autoreactive CD4+ T helper cells, which activate, proliferate, and trigger TSHR-Abs-producing plasma cells. Once exposed to a specific antigen, naive CD4+ T cells can differentiate in proinflammatory (Th17) or immunosuppressive (Treg) subsets. Infiltrating Th17 cells play a key role by producing proinflammatory cytokines that, in turn, activate resident T cells. Innate immune cells have a dual role in the immune response, encompassing both antigen presentation to effector lymphocytes and promotion of inflammation by thyroid infiltration and cytokines release.

• #7 Graves Disease

  https://bio.davidson.edu/Courses/Immunology/Students/Spring2003/Breedlove/GravesDisease.html

  One of the hallmarks of Graves’ disease is the prevalence of a Th2 response rather than a Th1 or CD8 T cell response. The Th2 dominance is achieved through „abnormal” T cell-dependent B-cell activation, which leads to the release of cytokines specific for a Th2 response, particularly IL-10. […] Apoptosis is abnormally regulated during the course of Graves’ disease, and thyrocytes in affected individuals undergo lower-than-normal levels of apoptosis. These thyrocytes express subnormal levels of Fas and high levels of Bcl-2 (an anti-apoptotic protein). Conversely, thyroid-infiltrating lymphocytes (TILs) in Graves’ disease express high levels of both Fas and FasL and low levels of Bcl-2; TILs in Graves’ disease patients thus exhibit high levels of apoptosis. This abnormal apoptotic regulation suppresses the effects of infiltrating lymphocytes while allowing thyroid cells to persist longer than normal. These results contribute to hyperthyroidism.

• #8 Molecular Mechanisms in Autoimmune Thyroid Disease

  https://www.mdpi.com/2073-4409/12/6/918

  The interaction with APCs leads to the activation of TLs (CD4+) and the differentiation towards Tregs and Th (Th1, Th2, and Th17), with an imbalance in the Th1:Th2 ratio. For HT, the predominance is towards a Th1 response, whereas in GBD, the predominance is towards a Th2 response. […] These mechanisms involve cytokines/chemokines and/or cytotoxins. For HT, apoptosis and subsequent fibrosis lead to the presence of hypothyroidism, while in GBD, the persistent stimulation of the TSHR by its autoantibody (TRAb) induces hyperthyroidism, goiter, and extrathyroidal manifestations.

• #9 Graves disease | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/graves-disease?lang=us

  Graves disease results from an antibody-directed stimulation of the thyroid-stimulating hormone (TSH) receptor, with the production and release of T3 and T4, resulting in hyperthyroidism. […] The pathogenesis of Graves disease is not fully known. Genetic predisposition accounts for 80% of the risk of Graves disease, with environmental factors (e.g. smoking, iodine excess, selenium deficiency, vitamin D deficiency) accounting for the rest.

• #10 Graves Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/120619-overview

  The anti-sodium-iodide symporter, antithyroglobulin, and antithyroid peroxidase antibodies appear to have little role in the etiology of hyperthyroidism in Graves disease. However, they are markers of autoimmune disease against the thyroid. […] Intrathyroidal lymphocytic infiltration is the initial histologic abnormality in persons with autoimmune thyroid disease and can be correlated with the titer of thyroid antibodies. […] Besides being the source of autoantigens, the thyroid cells express molecules that mediate T cell adhesion and complement regulation (Fas and cytokines) that participate and interact with the immune system. […] Viral infection is an environmental factor linked to Graves disease. […] Several autoimmune thyroid disease susceptibility genes are considered to be linked to Graves disease, including CD40, CTLA-4, the thyroglobulin gene (TG), the TSH-receptor gene (TSHR), PTPN22, FOXP3, CD25, and VDR.

• #11 Graves Disease Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/120619-clinical

  Graves disease is autoimmune in etiology, and the immune mechanisms involved may be one of the following: […] The autoimmune process in Graves disease is influenced by a combination of environmental and genetic factors. […] Several autoimmune thyroid disease susceptibility genes have been identified: CD40, CTLA-4, TG, TSHR, and PTPN22. […] Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a major thyroid autoantibody susceptibility gene, and it is a negative regulator of T-cell activation and may play an important role in the pathogenesis of Graves disease. […] There is an association of a C/T SNP in the Kozak sequence of CD40 with Graves disease. […] The association of SNPs in PTPN22 varies among autoimmune diseases individually or as part of a haplotype, and the mechanisms by which PTPN22 confers susceptibility to Graves disease may differ from other autoimmune diseases.

• #12 Graves’ Disease: Pathophysiology, Genetics and Management | IntechOpen

  https://www.intechopen.com/chapters/76867

  The RNASET2-FGFR1OP-CCR6 region at 6q27 and an intergenic region at 4p14 are two new susceptibility loci that had been found. […] Moreover, thyroid-stimulating hormone receptor and major histocompatibility complex class II versions have strong associations with thyroid stimulating hormone receptor autoantibodies (TRAb)-positive GD. […] The production of inflammatory cytokines like Inter-leukin 6 (IL-6) and TNF-alpha by these cells after piling up in orbital tissues also contribute to the pathophysiology of thyroid eye disease (opthalmopathy). […] In a whole genome association study of more than 1500 individuals suffering from Graves Disease and equal controls, six susceptible loci which are (CTLA4; cytotoxic T-lymphocyte-associated protein 4, MHC; major histocompatibility complex, FCRl3; Fc receptor-like protein 3, TSHR; thyroid stimulating hormone receptor, RNASET2-FGFR1OP-CCR6 region at 6q27, and an intergenic region at 4p14) have been discovered to be associated with GD.

• #13 KEGG DISEASE: Graves disease

  https://www.genome.jp/dbget-bin/www_bget?ds:H00082

  Graves disease is a common form of chronic autoimmune thyroid disease (AITD), and is characterized by overstimulation of the thyroid gland with agonistic anti-thyrotropin (TSH) receptor autoantibodies. This overstimulation leads to follicular hypertrophy and hyperplasia, causing thyroid enlargement, as well as increases in thyroid hormone production and the fraction of triiodothyronine (T3) relative to thyroxine (T4) in thyroid secretion. […] Thyroid autoimmune diseases are regarded as polygenic disorders resulting from the combination of a genetic predisposition in conjunction with an environmental trigger. […] Two main approaches have been employed to locate susceptibility loci for AITD, namely case control candidate gene studies and genome-wide linkage screens. […] Case control candidate gene studies have been employed to investigate numerous genes for association with AITD, but to date, only the human leucocyte region (HLA) on chromosome 6p21 and the cytotoxic T lymphocyte associated 4 (CTLA-4) gene on chromosome 2q33 have been consistently shown to be associated with disease.

• #14 Graves Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448195/

  Several environmental factors including pregnancy (mainly postpartum), iodine excess, infections, emotional stress, smoking, and interferon alfa trigger immune responses on susceptible genes to eventually cause Graves disease. […] Graves’ orbitopathy (ophthalmopathy) is caused by inflammation, cellular proliferation and increased growth of extraocular muscles and retro-orbital connective and adipose tissues due to the actions of thyroid stimulating antibodies and cytokines released by cytotoxic T lymphocytes (killer cells). These cytokines and thyroid stimulating antibodies activate periorbital fibroblasts and preadipocytes, causing synthesis of excess hydrophilic glycosaminoglycans (GAG) and retro-orbital fat growth. Glycosaminoglycans cause muscle swelling by trapping water. These changes give rise to proptosis, diplopia, congestion, and periorbital edema. If left untreated, it eventually leads to irreversible fibrosis of the muscles.

• #15 Graves Disease Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/120619-clinical

  Alleles of intron 7 of the TSH-receptor gene (TSHR) have also been shown to contribute to susceptibility to Graves disease. […] Environmental factors associated with susceptibility are largely unproven. […] Graves disease has been associated with a variety of infectious agents such as Yersinia enterocolitica and Borrelia burgdorferi. […] Stress can be a factor for thyroid autoimmunity. […] Immune checkpoint inhibitors (eg, antiCTLA-4 antibody [ipilimumab], antiPD-1 antibodies [nivolumab, pembrolizumab, cemiplimab], antiPD-L1 antibodies [avelumab, atezolizumab, durvalumab]), interferon beta-1b, and IL-4, when used therapeutically, may cause Graves disease. […] Trauma to the thyroid has also been reported to be associated with Graves disease.

• #16 Graves’ disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/graves-disease/

  Other, nongenetic factors are also believed to play a role in Graves’ disease. These factors may trigger the condition in people who are at risk, although the mechanism is unclear. Potential triggers include changes in sex hormones (particularly in women), viral or bacterial infections, certain medications, and having too much or too little iodine (a substance critical for thyroid hormone production). Smoking increases the risk of eye problems and is associated with more severe eye abnormalities in people with Graves disease.

• #17 Regulatory T Cells in the Pathogenesis of Graves’ Disease

  https://www.mdpi.com/1422-0067/24/22/16432

  Changes in Treg function or frequency are expected to have an impact on the initiation and course of GD. Possible susceptibility genes are FOXP3, CTLA-4, and CD25, whose polymorphisms might impair Treg inhibitory functions or proliferation. The -3279AA genotype of the FOXP3 gene, which leads to defective transcription of the gene, was recognized in 11.3% of GD patients with persistent hyperthyroidism and was absent in those in remission. […] The balance between immune activation and regulation is a key determinant in the pathophysiology of GD. Dysregulation of Tregs, whether due to their depletion, impaired function, or defective site-specific recruitment, appears to play a pivotal role in GD pathology, but controversies have emerged in the available literature. Patient heterogeneity, variations in Treg markers employed for analysis, methodological discrepancies, and relatively small sample sizes might explain this controversy. While a more comprehensive characterization of Treg cells in GD is critical, existing research predominantly suggests an impairment in their suppressive efficacy, stemming from reduced Treg percentages or dysfunction.

• #18 Graves Disease – Thyrotoxicosis and Hyperthyroidism – Thyroid Gland Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.9.2.1.

  Graves disease (GD) is an autoimmune disease in which the thyroid-stimulating hormone (TSH) receptor (TSH-R) is the autoantigen. Stimulation of this receptor in the thyroid gland by TSH-R antibodies (TRAb) results in increased secretion of thyroid hormones, development of signs and symptoms of hyperthyroidism, thyroid hypertrophy, and vascular proliferation. The activation of cellular immune-response mechanisms against the same antigen present in orbital and skin fibroblasts results in the development of clinical symptoms that are not directly related to the thyroid gland. […] Elevated TRAb levels confirm an active autoimmune process in GD.

• #19 Graves Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448195/

  Several environmental factors including pregnancy (mainly postpartum), iodine excess, infections, emotional stress, smoking, and interferon alfa trigger immune responses on susceptible genes to eventually cause Graves disease. […] Graves’ orbitopathy (ophthalmopathy) is caused by inflammation, cellular proliferation and increased growth of extraocular muscles and retro-orbital connective and adipose tissues due to the actions of thyroid stimulating antibodies and cytokines released by cytotoxic T lymphocytes (killer cells). These cytokines and thyroid stimulating antibodies activate periorbital fibroblasts and preadipocytes, causing synthesis of excess hydrophilic glycosaminoglycans (GAG) and retro-orbital fat growth. Glycosaminoglycans cause muscle swelling by trapping water. These changes give rise to proptosis, diplopia, congestion, and periorbital edema. If left untreated, it eventually leads to irreversible fibrosis of the muscles.

• #20 Graves’ ophthalmopathy – Wikipedia

  https://en.wikipedia.org/wiki/Graves%27_ophthalmopathy

  Graves’ is an orbital autoimmune disease. The thyroid-stimulating hormone receptor (TSH-R) is an antigen found in orbital fat and connective tissue, and is a target for autoimmune assault. […] On histological examination, there is an infiltration of the orbital connective tissue by lymphocytes, plasmocytes, and mastocytes. The inflammation results in a deposition of collagen and glycosaminoglycans in the muscles, which leads to subsequent enlargement and fibrosis. There is also an induction of the lipogenesis by fibroblasts and preadipocytes, which causes enlargement of the orbital fat and extra-ocular muscle compartments. This increase in volume of the intraorbital contents within the confines of the bony orbit may lead to dysthyroid optic neuropathy (DON), increased intraocular pressures, proptosis, and venous congestion leading to chemosis and periorbital oedema. […] The expansion of the intraorbital soft tissue volume may also remodel the bony orbit and enlarge it, which may be a form of auto-decompression.

• #21 Graves Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/120619-overview

  The TSH receptor is detectable in orbital tissues, but whether it has a pathogenetic role in Graves ophthalmopathy is unclear. The insulin-like growth factor-1 (IGF1) receptor is overexpressed in orbital fibroblasts, B cells, and T cells of patients with Graves ophthalmopathy, and patients with this eye disorder may have circulating immunoglobulins that bind to IGF1 receptors. Activation of IGF1R will increase hyaluronan synthesis and cytokine release.

• #22 Teprotumumab Recommended for Approval in Europe

  https://themunicheye.com/teprotumumab-recommended-approval-europe-19849

  Graves’ disease is an autoimmune disorder that can lead to noticeable symptoms, including protruding eyes, known as exophthalmos. […] Teprotumumab works by targeting the insulin-like growth factor-1 receptor (IGF-1R), which plays a crucial role in the pathogenesis of TED.

• #23 Graves Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448195/

  Pathogenesis of other rare manifestations of Graves disease like pretibial myxedema and thyroid acropachy are poorly understood and are believed to be due to cytokines mediated stimulation of fibroblasts. Many symptoms of hyperthyroidism like tachycardia, sweating, tremors, lid lag, and stare are thought to be related to increased sensitivity to catecholamine.

• #24 Graves disease – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/graves-disease/

  Graves disease (GD) is an autoimmune condition in which TSH receptor autoantibodies stimulate the thyroid gland, resulting in increased thyroid hormone production. […] General mechanism: B and T cell-mediated autoimmunity production of stimulating immunoglobulin G (IgG) against TSH-receptor (TRAb; type II hypersensitivity reaction) thyroid function and growth hyperthyroidism and diffuse goiter. […] Thyroid-associated ophthalmopathy: activated B and T cells infiltrate retro-orbital space targeting orbital fibroblasts cytokine release (e.g. TNF-, IFN-) local inflammatory response fibroblast proliferation and differentiation to adipocytes production of hyaluronic acid and GAGs and increased amount of adipocytes increase in the volume of intraorbital fat and muscle tissues exophthalmos, lid retraction, disturbances in ocular motility (causing diplopia). […] Pretibial myxedema: dermal fibroblast stimulation and deposition of glycosaminoglycans in connective tissue.

• #25 Graves’ disease – Wikipedia

  https://en.wikipedia.org/wiki/Graves%27_disease

  The TSHr is expressed on the thyroid follicular cells of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4. […] The infiltrative exophthalmos frequently encountered has been explained by postulating that the thyroid gland and the extraocular muscles share a common antigen, which is recognized by the antibodies. […] Antibodies binding to the extraocular muscles would cause swelling behind the eyeball. […] The „orange peel” skin has been explained by the infiltration of antibodies under the skin, causing an inflammatory reaction and subsequent fibrous plaques. […] The three types of autoantibodies to the TSH receptor are: Thyroid stimulating immunoglobulins, Thyroid growth immunoglobulins, Thyrotrophin binding-inhibiting immunoglobulins.

• #26 Graves’ disease – Wikipedia

  https://en.wikipedia.org/wiki/Graves%27_disease

  These antibodies (mainly IgG) act as long-acting thyroid stimulants (LATS), activating the cells through a slower and more drawn out process compared to TSH, leading to an elevated production of thyroid hormone. […] Another effect of hyperthyroidism is bone loss from osteoporosis, caused by an increased excretion of calcium and phosphorus in the urine and stool.

• #27 Pathophysiology of Graves disease | PPT

  https://www.slideshare.net/slideshow/pathophysiology-of-graves-disease/231914357

  It is an autoimmune disease. There is trigger in production of antibodies. These antibodies have structural similarities to the thyroid stimulating hormone (TSH). These antibodies will bind to the thyroid stimulating hormone receptor (TSHR) instead of TSH. Binding of these antibodies leads to activation of this receptor. Once this receptor is activated, there is excess production of the hormone T3 and T4. This, in turn, causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter. […] The three types of autoantibodies to the TSH receptor currently recognized are: Thyroid stimulating immunoglobulins, Thyroid growth immunoglobulins, Thyrotrophin binding-inhibiting immunoglobulins.

• #28 Graves disease: latest understanding of pathogenesis and treatment options | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-024-01016-5

  Graves disease is the most common cause of hyperthyroidism in iodine-sufficient areas. The main responsible mechanism is related to autoantibodies that bind and activate the thyrotropin receptor (TSHR). […] The main mechanism responsible for Graves hyperthyroidism is the activation of the thyroid-stimulating hormone receptor (TSHR) by autoantibodies that act as agonists, causing thyrocyte proliferation and hyperfunction. […] None of the conventional treatments for Graves hyperthyroidism act on its pathogenesis; new molecules that target early recognition of TSHR peptides, T cell activation, B cell stimulation and survival, production of TSHR autoantibodies, and TSHR activation have been tested with encouraging results. […] Graves orbitopathy is characterized by immune-mediated inflammatory reactions against autoantigens shared by thyroid epithelial cells and orbital fibroblasts; intravenous glucocorticoids are, to date, the first-line treatments for Graves orbitopathy. […] New target-based therapies that block pro-inflammatory cytokine receptors, lymphocytic infiltration or the insulin-like growth factor 1 receptor (IGF1R) have been tested in several clinical trials and show promising results in Graves orbitopathy.

• #29 Graves’ Disease: Novel Diagnostic Approaches and Emerging Treatment Options | IntechOpen

  https://www.intechopen.com/online-first/1197347

  The CD40-CD154 interaction between B and T lymphocytes is believed to play a crucial role in the development of Graves hyperthyroidism. […] The CD40 Kozak SNP allele, associated with Graves disease, enhances the translation efficiency of CD40 mRNA, potentially increasing disease susceptibility. […] The role of iscalimab has been best studied in an RCT, where it proved to be effective.

• #30 Graves’ Disease: Can It Be Cured?

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2019.34.1.29

  Whether or not Graves’ hyperthyroidism can be really cured, depends on the definition of cure. […] The natural history of Graves’ hyperthyroidism is not well known. […] We can influence the course of Graves’ hyperthyroidism by Tx, RAI, or ATD. Do these interventions really change the natural course of Graves’ hyperthyroidism? Is the disease cured after a successful intervention? […] If surgery is chosen for Graves’ hyperthyroidism, current guidelines recommend total thyroidectomy (TTx) as the procedure of choice rather than subtotal thyroidectomy (STTx). […] One may conclude that TTx is capable to definitively cure the hyperthyroid state, but at the expense of creating another diseasehypothyroidism. […] American Thyroid Association (ATA) guidelines stipulate the goal of RAI therapy (like that of surgery) in Graves’ disease is to control hyperthyroidism by rendering the patient hypothyroid.

• #31 Graves’ Disease: Can It Be Cured?

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2019.34.1.29

  One can conclude that elimination of Graves’ hyperthyroidism can be reached by RAI (although often a second or sometimes a third dose of 131I is required), but at the expense of a substantial risk of worsening or developing GO and creating a new diseasehypothyroidism. […] The mechanisms by which ATD induce a remission, are not completely understood. […] It reflects the notion that Graves’ hyperthyroidism is not really cured as long as TSH receptor antibodies are present, and I quite agree with this line of thinking. […] Whether or not Graves’ hyperthyroidism can be cured, depends on the definition of cure. If cure is defined as just disappearance of thyroid hormone excess, then cure is possible in almost all cases by either Tx, RAI, or ATD. […] The cure rate would be even lower if cure also supposes the absence of TSH receptor antibodies.

• #32 Graves’ Disease : Pathogenesis and Treatment in SearchWorks catalog

  https://searchworks.stanford.edu/view/14001742

  From the perspective of the investigator, Graves’ disease is a fascinating disorder with unique features and opportunities for study. […] The discovery in 1956 that Graves’ disease was caused by a humoral factor, later shown to be an antibody to the TSH receptor, was a triumph for modern investigative medicine. Rapid progress is now being made in (i) understanding the molecular interaction between autoantibodies and the TSH receptor, (ii) identifying the genes that contribute to the predisposition to disease, (iii) developing an animal model of Graves’ disease, and (iv) identifying the long-sought orbital antigen in ophthalmopathy. […] It is hoped that rapid progress in understanding the pathogenesis of the disease will lead to the ultimate goal of some form of immunotherapy that will make antithyroid drugs, radioiodine and thyroidectomy obsolete.

• #33 Graves’ Disease: Pathogenesis and Treatment | SpringerLink

  https://link.springer.com/book/10.1007/978-1-4615-4407-4

  From the perspective of the investigator, Graves’ disease is a fascinating disorder with unique features and opportunities for study. The discovery in 1956 that Graves’ disease was caused by a humoral factor, later shown to be an antibody to the TSH receptor, was a triumph for modern investigative medicine. Rapid progress is now being made in (i) understanding the molecular interaction between autoantibodies and the TSH receptor, (ii) identifying the genes that contribute to the predisposition to disease, (iii) developing an animal model of Graves’ disease, and (iv) identifying the long-sought orbital antigen in ophthalmopathy. […] It is hoped that rapid progress in understanding the pathogenesis of the disease will lead to the ultimate goal of some form of immunotherapy that will make antithyroid drugs, radioiodine and thyroidectomy obsolete.

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