Editing Hashimoto's thyroiditis (section)

==Mechanism==
The [[pathophysiology]] of autoimmune thyroiditis is not well understood.<ref name="Ramos-Levi2023">{{Cite book | vauthors = Ramos-Levi AM, Marazuela M |title=DeGroot's Endocrinology, Basic Science and Clinical Practice |publisher=Elsevier |year=2023 |isbn=978-0-323694124 |edition=8th |location=Philadelphia, PA |pages=1214–1233 |language=English |chapter=Thyroiditis |ref=Ramos-Levi2023}}</ref> However, once the disease is established, its core processes have been observed:

Hashimoto's thyroiditis is a [[T-lymphocyte]] mediated [[Autoimmunity|attack]] on the thyroid gland.<ref name="Klubo-Gwiezdzinska-2022" /> [[T helper cell|T helper 1 cells]] trigger [[Macrophage|macrophages]] and [[Cytotoxic t-lymphocytes|cytotoxic lymphocytes]] to destroy [[Thyroid follicular cell|thyroid follicular cells]], while T helper 2 cells stimulate the excessive production of [[B cell|B cells]] and [[Plasma cell|plasma cells]] which generate [[Antibody|antibodies]] against the thyroid [[Antigen|antigens]], leading to thyroiditis.<ref name="ref 4" /> The three major antibodies are: [[Thyroid peroxidase]] Antibodies (TPOAb), [[Thyroglobulin]] Antibodies (TgAb), and [[Thyroid stimulating hormone receptor]] Antibodies (TRAb),<ref name="Dayan96" /> with TPOAb and TgAb being most commonly implicated in Hashimotos.<ref name="Ramos-Levi2023" /> They are hypothesized to develop as a result of thyroid damage, where T-lymphocytes are sensitized to residual thyroid peroxidase and thyroglobulin, rather than as the initial cause of thyroid damage.<ref name="Ramos-Levi2023" /> However, they may exacerbate further thyroid destruction by binding the [[complement system]] and triggering [[apoptosis]] of thyroid cells.<ref name="Ramos-Levi2023" /> TPO antibody levels may correlate with the degree of [[lymphocyte]] infiltration of the thyroid.<ref>{{cite journal | vauthors = Yan YR, Gao XL, Zeng J, Liu Y, Lv QG, Jiang J, Huang H, Tong NW | title = The association between thyroid autoantibodies in serum and abnormal function and structure of the thyroid | journal = The Journal of International Medical Research | volume = 43 | issue = 3 | pages = 412–423 | date = June 2015 | pmid = 25855591 | doi = 10.1177/0300060514562487 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Teti C, Panciroli M, Nazzari E, Pesce G, Mariotti S, Olivieri A, Bagnasco M | title = Iodoprophylaxis and thyroid autoimmunity: an update | journal = Immunologic Research | volume = 69 | issue = 2 | pages = 129–138 | date = April 2021 | pmid = 33914231 | pmc = 8106604 | doi = 10.1007/s12026-021-09192-6 }}</ref>

Gross morphological changes within the thyroid are seen in the general enlargement, which is far more locally nodular and irregular than more diffuse patterns (such as that of [[hyperthyroidism]]). While the capsule is intact and the gland itself is still distinct from surrounding tissue, microscopic examination can provide a more revealing indication of the level of damage.<ref name="Maitra 2014 The Endocrine System">{{cite book |title=Robbins and Cotran Pathologic Basis of Disease |vauthors=Maitra A |date=2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-29635-9 |veditors=Kumar V, Abbas AK, Aster JC |pages=1073–1140 |chapter=The Endocrine System}}</ref> Hypothyroidism is caused by replacement of follicular cells with [[Parenchyma|parenchymatous tissue]].<ref name="ref 4">{{cite journal | vauthors = Berghi NO | title = Immunological Mechanisms Implicated in the Pathogenesis of Chronic Urticaria and Hashimoto Thyroiditis | journal = Iranian Journal of Allergy, Asthma, and Immunology | volume = 16 | issue = 4 | pages = 358–366 | date = August 2017 | pmid = 28865416 | url = https://ijaai.tums.ac.ir/index.php/ijaai/article/view/984 | url-status = live | access-date = 3 December 2020 | archive-url = https://web.archive.org/web/20210419162834/https://ijaai.tums.ac.ir/index.php/ijaai/article/view/984 | archive-date = 19 April 2021 }}</ref>

Partial regeneration of the thyroid tissue can occur, but this has not been observed to normalise hormonal levels.<ref>{{cite journal | vauthors = Romitti M, Costagliola S | title = Progress Toward and Challenges Remaining for Thyroid Tissue Regeneration | journal = Endocrinology | volume = 164 | issue = 10 | pages = bqad136 | date = August 2023 | pmid = 37690118 | pmc = 10516459 | doi = 10.1210/endocr/bqad136 }}</ref><ref name="Ushakov-2024">{{Cite journal | vauthors = Ushakov AV |date=September 2024 |title=Ultrasound signs of large segmental thyroid regeneration in Hashimoto's thyroiditis: a case report of two cases |url=https://aot.amegroups.com/article/view/7822/html |journal=Annals of Thyroid |volume=9 |pages=5 |doi=10.21037/aot-24-17|doi-access=free }}</ref> 

=== Pathology ===
[[File:Hashimoto's thyroiditis, HE 3.jpg|thumb|Marked lympocytic infiltration (purple areas) of the thyroid gland in a patient with chronic autoimmune thyroiditis]]
[[File:Hashimoto thyroiditis -- high mag.jpg|thumb|High powered magnification showing lymphocytic infiltration of the thyroid gland in autoimmune thyroiditis]]
Gross pathology of a thyroid with autoimmune thyroiditis may show an symmetrically enlarged thyroid.<ref name="Ramos-Levi2023" /> It is often paler in color, in comparison to normal thyroid tissue which is reddish-brown.<ref name="Ramos-Levi2023" /> 

Microscopic examination ([[histology]]) will show lymphocytes (including [[Plasma cell|plasma B-cells]]) diffusely infiltrating the [[parenchyma]].<ref name="Maitra 2014 The Endocrine System" /> The lymphocytes are predominately T-lymphocytes with a representation of both [[CD4+ cells|CD4+]] and [[CD8+]] cells.<ref name="Ramos-Levi2023" /> The plasma cells are [[Polyclonal B cell response|polyclonal]], with present [[Germinal center|germinal centers]] resembling the structure of a [[lymph node]]<ref name="Ramos-Levi2023" /> (also called secondary lymphoid follicles, not to be confused with the normally present [[colloid]]-filled [[Thyroid follicle|follicles]] that constitute the thyroid).<ref name="Maitra 2014 The Endocrine System" /> 

In late stages of the disease, the thyroid may be [[Atrophy|atrophic]].<ref name="Mincer2022" /> Colloid-filled follicles shrink and the cuboidal cells that usually line the follicles become [[Hürthle cell|Hürthle cells]].<ref name="Ramos-Levi2023" /> Fibrous tissue may be found throughout the affected thyroid as well.<ref name="Ramos-Levi2023" /> Severe thyroid atrophy presents often with denser fibrotic bands of [[collagen]] that remains within the confines of the thyroid capsule.<ref name="Maitra 2014 The Endocrine System" /> 

Generally, pathological findings of the thyroid are related to the amount of existing thyroid function — the more infiltration and fibrosis, the less likely a patient will have normal thyroid function.<ref name="Ramos-Levi2023" /> A rare but serious complication is [[thyroid lymphoma]], generally the B-cell type, [[non-Hodgkin lymphoma]].<ref name="Dayan96" />