Riedel's thyroiditis pathophysiology: Difference between revisions
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*Tissue [[eosinophilia]] and [[Major basic protein]] (MBP) identified in the thyroid gland on the [[histopathological]] analysis are also thought to play a role in the proliferation of [[fibroblasts]].<ref name="urlTissue eosinophilia and eosinophil degranulation in Riedels invasive fibrous thyroiditis | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic">{{cite web |url=https://doi.org/10.1210/jcem.81.3.8772560 |title=Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic |format= |work= |accessdate=}}</ref> | *Tissue [[eosinophilia]] and [[Major basic protein]] (MBP) identified in the thyroid gland on the [[histopathological]] analysis are also thought to play a role in the proliferation of [[fibroblasts]].<ref name="urlTissue eosinophilia and eosinophil degranulation in Riedels invasive fibrous thyroiditis | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic">{{cite web |url=https://doi.org/10.1210/jcem.81.3.8772560 |title=Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic |format= |work= |accessdate=}}</ref> | ||
*A shared mechanism with [[retroperitoneal fibrosis]] and [[sclerosing cholangitis]] is also suggested.<ref name="pmid8504980">{{cite journal |author=De Boer WA |title=Riedel's thyroiditis, retroperitoneal fibrosis, and sclerosing cholangitis: diseases with one pathogenesis? |journal=Gut |volume=34 |issue=5 |pages=714 |year=1993|pmid=8504980 |pmc=1374200 |doi= |url=http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=8504980}}</ref> | *A shared mechanism with [[retroperitoneal fibrosis]] and [[sclerosing cholangitis]] is also suggested.<ref name="pmid8504980">{{cite journal |author=De Boer WA |title=Riedel's thyroiditis, retroperitoneal fibrosis, and sclerosing cholangitis: diseases with one pathogenesis? |journal=Gut |volume=34 |issue=5 |pages=714 |year=1993|pmid=8504980 |pmc=1374200 |doi= |url=http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=8504980}}</ref> | ||
===Hypotheses | ===Hypotheses=== | ||
The following hypotheses regarding the pathogenesis of Riedel's thyroiditis have been proposed:<ref name="pmid15298150">{{cite journal |vauthors=Papi G, LiVolsi VA |title=Current concepts on Riedel thyroiditis |journal=Am. J. Clin. Pathol. |volume=121 Suppl |issue= |pages=S50–63 |year=2004 |pmid=15298150 |doi= |url=}}</ref> | The following hypotheses regarding the pathogenesis of Riedel's thyroiditis have been proposed:<ref name="pmid15298150">{{cite journal |vauthors=Papi G, LiVolsi VA |title=Current concepts on Riedel thyroiditis |journal=Am. J. Clin. Pathol. |volume=121 Suppl |issue= |pages=S50–63 |year=2004 |pmid=15298150 |doi= |url=}}</ref> | ||
====The Systemic Autoimmune Hypothesis==== | ====The Systemic Autoimmune Hypothesis==== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Furqan M M. M.B.B.S[2]
Overview
The exact pathogenesis of Riedel's thyroiditis is not fully understood. The presence of thyroid autoantibodies and lymphoid infiltration of the thyroid gland resembling that of Hashimoto's thyroiditis might indicate an autoimmune etiology. It is considered that the infiltrating lymphocytes release cytokines which are responsible for the activation of fibroblasts responsible for the fibrosis. Riedel's thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis that invades adjacent structures of the neck and extends beyond the thyroid capsule. This makes the thyroid gland stone-hard and fixed to adjacent structures. A shared mechanism with retroperitoneal fibrosis and sclerosing cholangitis has been suggested.
Pathophysiology
The control, synthesis, and release of the thyroid hormone is usually controlled by hypothalamus and pituitary gland.[1][2]
- Thyroid hormones (T3 and T4) are regulating basal metabolic rate, influence oxygen consumption by tissues. They are crucial for normal development of the brain and growth of the body.
- Secretion of thyroid hormones follows upper control from the hypothalamus and the pituitary. Thyroid releasing hormone (TRH) acts on thyrotropes releasing cells in the pituitary causing them to release thyroid stimulating hormone (TSH).
- TSH acts on thyroid gland by binding to specific membrane receptors and activating an intracellular pathway involving cAMP that ends in the formation and secretion of thyroid hormones.
- Iodine is essential for the synthesis of thyroid hormones. Iodide is up taken through a special Na/I transporter found in the membrane of thyroid follicular cell. After the iodide uptake, it goes through a series of organic reactions ending in the formation of the two forms of thyroid hormones: T3 and T4. T3 and T4 remain stored in the thyroglobulin of the follicles and are released in response to further stimulation by TSH to the thyroid follicles.
- While T3 is 3 to 5 times more potent than T4, it represents only one-fourth of the total hormone secretion. T3 is thought to be the biologically active form of the hormone. Most of the circulating T3 is due to peripheral conversion of T4 in the liver and peripheral tissues while only a small percentage is secreted directly from the thyroid gland itself.
- T3 and T4 act on nuclear receptors (DNA binding proteins) and cause the regulate the transcription of many proteins to regulate the metabolic rate of the body.
- The higher regulation of thyroxine secretion follows the negative feedback role, meaning that high levels of T3 and T4 will suppress TRH and TSH secretion and vice versa (Low levels of thyroxine will stimulate TRH and TSH secretion). This is useful in diagnosing the cause of hyperthyroidism.
- TSH will be low in primary hyperthyroidism where the gland is the source of the excess hormones. In secondary hyperthyroidism, TSH will be high as the pituitary or the hypothalamus are the sources of the disease.
Pathogenesis
The exact pathogenesis of Riedel's thyroiditis is not fully understood. The presence of thyroid autoantibodies and lymphoid infiltration of the thyroid gland resembling that of Hashimoto's thyroiditis might indicate an autoimmune etiology.[3]
- It is considered that the infiltrating lymphocytes (CD4+ and CD8+) release cytokines which are responsible for the activation of fibroblasts responsible for the fibrosis.[4]
- Riedel's thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis that invades adjacent structures of the neck and extends beyond the thyroid capsule.This makes the thyroid gland stone-hard and fixed to adjacent structures.[5]
- Tissue eosinophilia and Major basic protein (MBP) identified in the thyroid gland on the histopathological analysis are also thought to play a role in the proliferation of fibroblasts.[6]
- A shared mechanism with retroperitoneal fibrosis and sclerosing cholangitis is also suggested.[7]
Hypotheses
The following hypotheses regarding the pathogenesis of Riedel's thyroiditis have been proposed:[8]
The Systemic Autoimmune Hypothesis
According to this theory, Riedel's thyroiditis might be a primary disease of fibroblasts triggered by autoimmune stimuli.[8][9][10][11][12][13]
- It is proposed that the endothelial cells release oxidized low-density lipoprotein from atheromatous plaques following the injury resulting in an allergic hypersensitivity reaction.
- The natural consequence of this hypothesis is that the antigen initiating fibrosis is not localized within the thyroid but is affected secondarily by a systemic fibroinflammatory process.
- Thyroid follicular cells, peri-thyroid muscular cells, or intrathyroidal endothelial cells express antigens, cytokines, or adhesion molecules that might contribute to local activation of the disease. The evidence of a perivascular concentration of inflammatory cells in RT (occlusive phlebitis) might support the theory that the allergic process first involves blood vessels.
- Once the allergic reaction has started, a heavy inflammatory cell population such as B and T lymphocytes, plasma cells, monocytes, and eosinophils infiltrate tissues and produce several cytokines.
- The role of eosinophils in this context probably is central. When eosinophils migrate into the tissues involved by the disease, they degranulate and release cationic toxins into connective tissue including Major basic protein (MBP), eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin.
- Eosinophils also release cytokines, the most important of which are transforming growth factor β, transforming growth factor α, and granulocyte-macrophage colony-stimulating factor. This stimulates fibroblast proliferation that finally causes fibrosis.
The Genetic Hypothesis
This hypothesis was proposed for the multifocal fibrosclerosis which is associated with Riedel's thyroiditis.[14]
- The basis of this hypothesis was a report of multifocal fibrosclerotic disease in two brothers, whose parents were first cousins. They developed different combinations of the multifocal fibrosclerotic disease and a familial multifocal fibrosclerosis was hypothesized.
- It was thought that genetic factors might have played a partial role in an enzymatic defect in the tryptophan → serotonin → 5-hydroxyindolacetic acid pathway. However, such a relationship has never been proven, and the siblings described remain the only case of familial multifocal fibrosclerosis reported in the literature.
The Intrathyroidal hypothesis
Riedel's thyroiditis is associated with Hashimoto's thyroiditis and de Quervain's thyroiditis.[15]
- It is proposed that Riedel's thyroiditis might represent a late fibrotic stage of subacute or chronic thyroiditis. The fundamental concept of this theory is that the fibrosing process of RT is specific to the thyroid gland.
The Pharmacologic Hypothesis
This hypothesis is also proposed primarily for multifocal fibrosclerosis. As Riedel's thyroiditis is associated with multifocal fibrosclerosis this theory might explain the indirect association of Riedel's thyroiditis with drugs.[8][16]
- The production of fibrosis by the drugs might be determined by an increased serum serotonin concentration through competitive inhibition at the serotonin receptor level and a reaction of hypersensitivity causing vasculitis, plasmatic exudation resulting in fibrosis.
- Although drugs have been found to cause multi organ fibrosis, there are no reports of the association of Riedel's thyroiditis caused by drugs. This theory might explain the indirect association of Riedel's thyroiditis with drugs as Riedel's thyroiditis is associated with multifocal fibrosclerosis.
Associated Conditions
Riedel's thyroiditis is associated various other autoimmune conditions including:[4][17][18][19][20][16]
- Graves’ disease
- Hashimoto’s thyroiditis
- Multifocal idiopathic fibrosclerosis
- Addison’s disease
- Pernicious anemia
- Type 1 diabetes
Gross Pathology
- On gross pathology, dense, avascular white fibrous tissue, the absence of a capsule, and no normal thyroid tissue are characteristic findings of Riedel's thyroiditis.[21]
Microscopic Pathology
- On microscopic histopathological analysis, destruction of thyroid follicle by inflammatory cells and fibrous tissues and invasion of surrounding structures are characteristic findings of Riedel's thyroiditis.The inflammatory cells including lymphocytes, plasma cells, and eosinophils are present in a dense matrix of hyalinized connective tissue.[22][8]
Gallery
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Histology of Riedel's thyroiditis (Image courtesy of AFIP and PathologyOutlines.com; http://www.pathologyoutlines.com/topic/thyroidriedel.html ) -
Histology of Riedel's thyroiditis (Image courtesy of AFIP and PathologyOutlines.com; http://www.pathologyoutlines.com/topic/thyroidriedel.html ) -
Histology of Riedel's thyroiditis (Image courtesy of AFIP and PathologyOutlines.com; http://www.pathologyoutlines.com/topic/thyroidriedel.html )
References
- ↑ De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Rousset B, Dupuy C, Miot F, Dumont J. "Thyroid Hormone Synthesis And Secretion". PMID 25905405.
- ↑ Kirsten D (2000). "The thyroid gland: physiology and pathophysiology". Neonatal Netw. 19 (8): 11–26. doi:10.1891/0730-0832.19.8.11. PMID 11949270.
- ↑ Schwaegerle SM, Bauer TW, Esselstyn CB (1988). "Riedel's thyroiditis". Am. J. Clin. Pathol. 90 (6): 715–22. PMID 3057862.
- ↑ 4.0 4.1 Zimmermann-Belsing T, Feldt-Rasmussen U (1994). "Riedel's thyroiditis: an autoimmune or primary fibrotic disease?". J. Intern. Med. 235 (3): 271–4. PMID 8120524.
- ↑ Cho MH, Kim CS, Park JS; et al. (2007). "Riedel's thyroiditis in a patient with recurrent subacute thyroiditis: a case report and review of the literature". Endocr. J. 54 (4): 559–62. PMID 17603227.
- ↑ "Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic".
- ↑ De Boer WA (1993). "Riedel's thyroiditis, retroperitoneal fibrosis, and sclerosing cholangitis: diseases with one pathogenesis?". Gut. 34 (5): 714. PMC 1374200. PMID 8504980.
- ↑ 8.0 8.1 8.2 8.3 Papi G, LiVolsi VA (2004). "Current concepts on Riedel thyroiditis". Am. J. Clin. Pathol. 121 Suppl: S50–63. PMID 15298150.
- ↑ Heufelder AE, Goellner JR, Bahn RS, Gleich GJ, Hay ID (1996). "Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis". J. Clin. Endocrinol. Metab. 81 (3): 977–84. doi:10.1210/jcem.81.3.8772560. PMID 8772560.
- ↑ Noguchi H, Kephart GM, Colby TV, Gleich GJ (1992). "Tissue eosinophilia and eosinophil degranulation in syndromes associated with fibrosis". Am. J. Pathol. 140 (2): 521–8. PMC 1886427. PMID 1739138.
- ↑ Gleich GJ, Adolphson CR (1986). "The eosinophilic leukocyte: structure and function". Adv. Immunol. 39: 177–253. PMID 3538819.
- ↑ Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D (1979). "Cytotoxic properties of the eosinophil major basic protein". J. Immunol. 123 (6): 2925–7. PMID 501097.
- ↑ Seibold JR, Giorno RC, Claman HN (1990). "Dermal mast cell degranulation in systemic sclerosis". Arthritis Rheum. 33 (11): 1702–9. PMID 2242067.
- ↑ Comings DE, Skubi KB, Van Eyes J, Motulsky AG (1967). "Familial multifocal fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal fibrosis, sclerosing cholangitis, Riedel's thyroiditis, and pseudotumor of the orbit may be different manifestations of a single disease". Ann. Intern. Med. 66 (5): 884–92. PMID 6025229.
- ↑ Ewing J (1919). Neoplastic Diseases 2nd edition. Saunders; 1922:908.
- ↑ 16.0 16.1 Drieskens O, Blockmans D, Van den Bruel A, Mortelmans L (2002). "Riedel's thyroiditis and retroperitoneal fibrosis in multifocal fibrosclerosis: positron emission tomographic findings". Clin Nucl Med. 27 (6): 413–5. PMID 12045432.
- ↑ Drury MI, Sweeney EC, Heffernan SJ (1974). "Invasive fibrous (Riedel's) thyroiditis". Ir Med J. 67 (14): 388–90. PMID 4413980.
- ↑ "Chronic thyroiditis: A case showing features of both riedel's and hashimoto's thyroiditis - Merrington - 1948 - British Journal of Surgery - Wiley Online Library".
- ↑ Hines RC, Scheuermann HA, Royster HP (1970). "Invasive Fibrous (Riedel's) Thyroiditis With Bilateral Fibrous Parotitis". JAMA: 869–871. doi:10.1001/jama.1970.03170310147054.
- ↑ "Riedel's Thyroiditis: A Clinical Review | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic".
- ↑ "Riedel's Thyroiditis | American Journal of Clinical Pathology | Oxford Academic".
- ↑ "Redirecting".