hashimoto's thyroiditis

File:Signs and symptoms of hypothyroidism.png

File:Hypothyroidism.jpgIn the early stages of autoimmune thyroiditis, patients may have normal thyroid hormone levels and no goiter or a small one. Enlargement of the thyroid is due to lymphocytic infiltration and fibrosis.{{cite journal | vauthors = Klubo-Gwiezdzinska J, Wartofsky L | title = Hashimoto thyroiditis: an evidence-based guide to etiology, diagnosis and treatment | journal = Polish Archives of Internal Medicine | volume = 132 | issue = 3 | pages = 16222 | date = March 2022 | pmid = 35243857 | pmc = 9478900 | doi = 10.20452/pamw.16222 }} Early on, thyroid autoantibodies in the blood may be the only indication of Hashimoto’s disease. They are thought to be the secondary products of the T cell-mediated destruction of the gland.

As lymphocytic infiltration progresses, patients may exhibit signs of hypothyroidism in multiple bodily systems, including, but not limited to, a larger goiter, weight gain, cold intolerance, fatigue, myxedema, constipation, menstrual disturbances, pale or dry skin, and dry, brittle hair, depression, and ataxia.{{Cite book |title=The Washington Manual, The Endocrinology - Subspecialty Consult |vauthors=Singh S, Clutter WE |publisher=Lippincott Williams & Wilkins |year=2020 |isbn=978-1-9751-1333-9 |edition=4th |location=Philadelphia, PA |pages=70–76 |language=English}} Extended thyroid hormone deficiency may lead to muscle fibre changes, resulting in muscle weakness, muscle pain, stiffness, and rarely, pseudohypertrophy.{{cite book | vauthors = Fariduddin MM, Haq N, Bansal N | chapter = Hypothyroid Myopathy |date=2024 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK519513/ |access-date=2024-11-30 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30137798}} Patients with goiters who have had autoimmune thyroiditis for many years might see their goiter shrink in the later stages of the disease due to destruction of the thyroid. Graves disease may occur before or after the development of autoimmune thyroiditis.{{Cite book |title=Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text |vauthors=Weetman AP |publisher=Lippincott Williams & Wilkins |year=2021 |isbn=978-1-975112-96-7 |edition=11th |location=Philadelphia, PA |pages=531–541 |language=English}}

While rare, more serious complications of the hypothyroidism resulting from autoimmune thyroiditis are pericardial effusion, pleural effusion, both of which require further medical attention, and myxedema coma, which is an endocrine emergency.

Many symptoms are attributed to the development of Hashimoto's thyroiditis. Symptoms can include: fatigue, weight gain, pale or puffy face, feeling cold, joint and muscle pain, constipation, dry and thinning hair, heavy menstrual flow or irregular periods, depression, a slowed heart rate, problems getting pregnant, miscarriages,{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/hashimotos-disease/symptoms-causes/syc-20351855|title=Hashimoto's disease – Symptoms and causes|work=Mayo Clinic|access-date=2018-10-05|language=en|archive-date=29 October 2018|archive-url=https://web.archive.org/web/20181029084838/https://www.mayoclinic.org/diseases-conditions/hashimotos-disease/symptoms-causes/syc-20351855|url-status=live}} and myopathy. Some patients in the early stage of the disease may experience symptoms of hyperthyroidism due to the release of thyroid hormones from intermittent thyroid destruction{{cite journal | vauthors = Dyrka K, Obara-Moszyńska M, Niedziela M | title = Autoimmune thyroiditis: an update on treatment possibilities | journal = Endokrynologia Polska | volume = 75 | issue = 5 | pages = 461–472 | date = 2024 | pmid = 39475129 | doi = 10.5603/ep.100701 | doi-access = free }} (also called "destructive thyrotoxicosis"). In non-medical settings, the term "flare" is used to refer to a sudden exacerbation of symptoms, whether hyper or hypo.{{Cite web |title=Hashimoto's Thyroiditis: Symptoms, Causes, and Treatments |url=https://www.webmd.com/women/hashimotos-thyroiditis-symptoms-causes-treatments |access-date=2025-01-08 |website=WebMD |language=en |vauthors=Dunkin MA}}

While most symptoms are attributed to hypothyroidism, similar symptoms are observed in Hashimoto's patients with normal thyroid hormone levels.{{Cite book | vauthors = Jonklaas J |title=DeGroot's Endocrinology: Basic Science and Clinical Practice |year=2023 |isbn=978-0-323-69412-4 |edition=8th |pages=1234–1248 |chapter=Hypothyroidism|publisher=Elsevier Health Sciences }} According to one study, these symptoms may include lower quality of life, and issues of the "digestive system (abdominal distension, constipation and diarrhea), endocrine system (chilliness, gain weight and facial edema), neuropsychiatric system (forgetfulness, anxiety, depressed, fatigue, insomnia, irritability, and indifferent [sic]) and mucocutaneous system (dry skin, pruritus, and hair loss)."{{cite journal | vauthors = Li J, Huang Q, Sun S, Zhou K, Wang X, Pan K, Zhang Y, Wang Y, Han Q, Si C, Li S, Fan S, Li D | title = Thyroid antibodies in Hashimoto's thyroiditis patients are positively associated with inflammation and multiple symptoms | journal = Scientific Reports | volume = 14 | issue = 1 | pages = 27902 | date = November 2024 | pmid = 39537841 | pmc = 11561229 | doi = 10.1038/s41598-024-78938-7 | bibcode = 2024NatSR..1427902L }}

The causes of Hashimoto's thyroiditis are complex. Around 80% of the risk of developing an autoimmune thyroid disorder is due to genetic factors, while the remaining 20% is related to environmental factors (such as iodine, drugs, infection, stress, radiation).{{cite journal | vauthors = Casto C, Pepe G, Li Pomi A, Corica D, Aversa T, Wasniewska M | title = Hashimoto's Thyroiditis and Graves' Disease in Genetic Syndromes in Pediatric Age | journal = Genes | volume = 12 | issue = 2 | pages = 222 | date = February 2021 | pmid = 33557156 | pmc = 7913917 | doi = 10.3390/genes12020222 | doi-access = free }}

Thyroid autoimmunity can be familial.{{cite journal | vauthors = Dayan CM, Daniels GH | title = Chronic autoimmune thyroiditis | journal = The New England Journal of Medicine | volume = 335 | issue = 2 | pages = 99–107 | date = July 1996 | pmid = 8649497 | doi = 10.1056/nejm199607113350206 }} Many patients report a family history of autoimmune thyroiditis or Graves' disease. The strong genetic component is borne out in studies on monozygotic twins, with a concordance of 38–55%, with an even higher concordance of circulating thyroid antibodies not in relation to clinical presentation (up to 80% in monozygotic twins). Neither result was seen to a similar degree in dizygotic twins, offering strong favour for high genetic etiology.

The genes implicated vary in different ethnic groups and the impact of these genes on the disease differs significantly among people from different ethnic groups. A gene that has a large effect in one ethnic group's risk of developing Hashimoto's thyroiditis might have a much smaller effect in another ethnic group.

The incidence of autoimmune thyroid disorders is increased in people with chromosomal disorders, including Turner, Down, and Klinefelter syndromes.

The first gene locus associated with autoimmune thyroid disease was the major histocompatibility complex (MHC) region on chromosome 6p21. It encodes human leukocyte antigens (HLAs). Specific HLA alleles have a higher affinity to auto-antigenic thyroidal peptides and can contribute to autoimmune thyroid disease development. Specifically, in Hashimoto's disease, aberrant expression of HLA II on thyrocytes has been demonstrated. They can present thyroid autoantigens and initiate autoimmune thyroid disease.{{cite journal | vauthors = Jacobson EM, Huber A, Tomer Y | title = The HLA gene complex in thyroid autoimmunity: from epidemiology to etiology | journal = Journal of Autoimmunity | volume = 30 | issue = 1–2 | pages = 58–62 | date = 2008 | pmid = 18178059 | pmc = 2244911 | doi = 10.1016/j.jaut.2007.11.010 }} Susceptibility alleles are not consistent in Hashimoto's disease. In Caucasians, various alleles are reported to be associated with the disease, including DR3, DR5, and DQ7.{{cite journal | vauthors = Tandon N, Zhang L, Weetman AP | title = HLA associations with Hashimoto's thyroiditis | journal = Clinical Endocrinology | volume = 34 | issue = 5 | pages = 383–386 | date = May 1991 | pmid = 1676351 | doi = 10.1111/j.1365-2265.1991.tb00309.x | s2cid = 28987581 }}{{cite journal | vauthors = Bogner U, Badenhoop K, Peters H, Schmieg D, Mayr WR, Usadel KH, Schleusener H | title = HLA-DR/DQ gene variation in nongoitrous autoimmune thyroiditis at the serological and molecular level | journal = Autoimmunity | volume = 14 | issue = 2 | pages = 155–158 | date = January 1992 | pmid = 1363895 | doi = 10.3109/08916939209083135 }}

CTLA-4 is the second major immune-regulatory gene related to autoimmune thyroid disease. CTLA-4 gene polymorphisms may contribute to the reduced inhibition of T-cell proliferation and increase susceptibility to autoimmune response.{{cite journal | vauthors = Zaletel K, Gaberšček S | title = Hashimoto's Thyroiditis: From Genes to the Disease | journal = Current Genomics | volume = 12 | issue = 8 | pages = 576–588 | date = December 2011 | pmid = 22654557 | pmc = 3271310 | doi = 10.2174/138920211798120763 }} CTLA-4 is a major thyroid autoantibody susceptibility gene. A linkage of the CTLA-4 region to the presence of thyroid autoantibodies was demonstrated by a whole-genome linkage analysis.{{cite journal | vauthors = Tomer Y, Greenberg DA, Barbesino G, Concepcion E, Davies TF | title = CTLA-4 and not CD28 is a susceptibility gene for thyroid autoantibody production | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 4 | pages = 1687–1693 | date = April 2001 | pmid = 11297604 | doi = 10.1210/jcem.86.4.7372 | doi-access = free }} CTLA-4 was confirmed as the main locus for thyroid autoantibodies.{{cite journal | vauthors = Ban Y, Davies TF, Greenberg DA, Kissin A, Marder B, Murphy B, Concepcion ES, Villanueva RB, Barbesino G, Ling V, Tomer Y | title = Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease | journal = Genes and Immunity | volume = 4 | issue = 8 | pages = 586–593 | date = December 2003 | pmid = 14647199 | doi = 10.1038/sj.gene.6364018 | s2cid = 6920190 | doi-access = }}

PTPN22 is the most recently identified immune-regulatory gene associated with autoimmune thyroid disease. It is located on chromosome 1p13 and expressed in lymphocytes. It acts as a negative regulator of T-cell activation. Mutation in this gene is a risk factor for many autoimmune diseases. Weaker T-cell signaling may lead to impaired thymic deletion of autoreactive T cells, and increased PTPN22 function may result in inhibition of regulatory T cells, which protect against autoimmunity.{{cite journal | vauthors = Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP | title = Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? | journal = FEBS Letters | volume = 585 | issue = 23 | pages = 3689–3698 | date = December 2011 | pmid = 21515266 | doi = 10.1016/j.febslet.2011.04.032 | s2cid = 21572847 | doi-access = free | bibcode = 2011FEBSL.585.3689B }}

IFN-γ promotes cell-mediated cytotoxicity against thyroid mutations causing increased production of IFN-γ were associated with the severity of hypothyroidism.{{cite journal | vauthors = Ito C, Watanabe M, Okuda N, Watanabe C, Iwatani Y | title = Association between the severity of Hashimoto's disease and the functional +874A/T polymorphism in the interferon-gamma gene | journal = Endocrine Journal | volume = 53 | issue = 4 | pages = 473–478 | date = August 2006 | pmid = 16820703 | doi = 10.1507/endocrj.k06-015 | doi-access = free }} Severe hypothyroidism is associated with mutations leading to lower production of IL-4 (Th2 cytokine suppressing cell-mediated autoimmunity),{{cite journal | vauthors = Nanba T, Watanabe M, Akamizu T, Iwatani Y | title = The -590CC genotype in the IL4 gene as a strong predictive factor for the development of hypothyroidism in Hashimoto disease | journal = Clinical Chemistry | volume = 54 | issue = 3 | pages = 621–623 | date = March 2008 | pmid = 18310157 | doi = 10.1373/clinchem.2007.099739 | doi-access = }} lower secretion of TGF-β (inhibitor of cytokine production),{{cite journal | vauthors = Yamada H, Watanabe M, Nanba T, Akamizu T, Iwatani Y | title = The +869T/C polymorphism in the transforming growth factor-beta1 gene is associated with the severity and intractability of autoimmune thyroid disease | journal = Clinical and Experimental Immunology | volume = 151 | issue = 3 | pages = 379–382 | date = March 2008 | pmid = 18190611 | pmc = 2276968 | doi = 10.1111/j.1365-2249.2007.03575.x }} and mutations of FOXP3, an essential regulatory factor for the regulatory T cells (Tregs) development.{{cite journal | vauthors = Inoue N, Watanabe M, Morita M, Tomizawa R, Akamizu T, Tatsumi K, Hidaka Y, Iwatani Y | title = Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases | journal = Clinical and Experimental Immunology | volume = 162 | issue = 3 | pages = 402–406 | date = December 2010 | pmid = 20942809 | pmc = 3026543 | doi = 10.1111/j.1365-2249.2010.04229.x }} Development of Hashimoto's disease was associated with mutation of the gene for TNF-α (stimulator of the IFN-γ production), causing its higher concentration.{{cite journal | vauthors = Inoue N, Watanabe M, Nanba T, Wada M, Akamizu T, Iwatani Y | title = Involvement of functional polymorphisms in the TNFA gene in the pathogenesis of autoimmune thyroid diseases and production of anti-thyrotropin receptor antibody | journal = Clinical and Experimental Immunology | volume = 156 | issue = 2 | pages = 199–204 | date = May 2009 | pmid = 19250279 | pmc = 2759465 | doi = 10.1111/j.1365-2249.2009.03884.x }}

Study of healthy Danish twins divided to three groups (monozygotic and dizygotic same sex, and opposite sex twin pairs) estimated that genetic contribution to thyroid peroxidase antibodies susceptibility was 61% in males and 72% in females, and contribution to thyroglobulin antibodies susceptibility was 39% in males and 75% in females.{{cite journal | vauthors = Hansen PS, Brix TH, Iachine I, Kyvik KO, Hegedüs L | title = The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins | journal = European Journal of Endocrinology | volume = 154 | issue = 1 | pages = 29–38 | date = January 2006 | pmid = 16381988 | doi = 10.1530/eje.1.02060 | s2cid = 25372591 | doi-access = }}

The high female predominance in thyroid autoimmunity may be associated with the X chromosome. It contains sex and immune-related genes responsible for immune tolerance.{{cite journal | vauthors = McCombe PA, Greer JM, Mackay IR | title = Sexual dimorphism in autoimmune disease | journal = Current Molecular Medicine | volume = 9 | issue = 9 | pages = 1058–1079 | date = December 2009 | pmid = 19747114 | doi = 10.2174/156652409789839116 }}

A higher incidence of thyroid autoimmunity was reported in patients with a higher rate of X-chromosome monosomy in peripheral white blood cells.{{cite journal | vauthors = Invernizzi P, Miozzo M, Selmi C, Persani L, Battezzati PM, Zuin M, Lucchi S, Meroni PL, Marasini B, Zeni S, Watnik M, Grati FR, Simoni G, Gershwin ME, Podda M | title = X chromosome monosomy: a common mechanism for autoimmune diseases | journal = Journal of Immunology | volume = 175 | issue = 1 | pages = 575–578 | date = July 2005 | pmid = 15972694 | doi = 10.4049/jimmunol.175.1.575 | s2cid = 40557667 | doi-access = free }} Another potential mechanism might be skewed X-chromosome inactivation.

In one population study, two or more births were a risk factor for developing autoimmune hypothyroidism in pre-menopausal women.{{cite journal | vauthors = Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Laurberg P | title = Development of autoimmune overt hypothyroidism is highly associated with live births and induced abortions but only in premenopausal women | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 99 | issue = 6 | pages = 2241–2249 | date = June 2014 | pmid = 24694338 | doi = 10.1210/jc.2013-4474 | doi-access = free }}

Certain medications or drugs have been associated with altering and interfering with thyroid function. There are two main mechanisms of interference:

• Altering thyroid hormone serum transfer proteins.{{cite journal | vauthors = Surks MI, Sievert R | title = Drugs and thyroid function | journal = The New England Journal of Medicine | volume = 333 | issue = 25 | pages = 1688–1694 | date = December 1995 | pmid = 7477223 | doi = 10.1056/NEJM199512213332507 | veditors = Wood AJ }} Estrogen, tamoxifen, heroin, methadone, clofibrate, 5-fluorouracil, mitotane, and perphenazine all increase thyroid binding globulin (TBG) concentration. Androgens, anabolic steroids such as danazol, glucocorticoids, and slow release nicotinic acid all decrease TBG concentrations. Furosemide, fenoflenac, mefenamic acid, salicylates, phenytoin, diazepam, sulphonylureas, free fatty acids, and heparin all interfere with thyroid hormone binding to TBG and/or transthyretin.
• Altering extra-thryoidal metabolism of thyroid hormone. Propylthiouracil, glucocorticoids, propranolol, iondinated contrast agents, amiodarone, and clomipramine all inhibit conversion of T₄ and T₃. Phenobarbital, rifampin, phenytoin and carbamazepine all increase hepatic metabolism. Finally, cholestryamine, colestipol, aluminium hydroxide, ferrous sulphate, and sucralfate are all drugs that decrease T₄ absorption or enhance excretion.

Both excessive and insufficient iodine intake has been implicated in developing antithyroid antibodies.{{Cite book | vauthors = Weetman AP, Kahaly GJ |title=DeGroot's Endocrinology |year=2023 |edition=8th |pages=1178-1193 |chapter=Graves Disease}} Thyroid autoantibodies are found to be more prevalent in geographical areas after increasing iodine levels. Several mechanisms by which excessive iodine may promote thyroid autoimmunity have been proposed:

• Via thyroglobulin iodination: Iodine exposure leads to higher iodination of thyroglobulin, increasing its immunogenicity{{cite journal | vauthors = Rayman MP | title = Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease | journal = The Proceedings of the Nutrition Society | volume = 78 | issue = 1 | pages = 34–44 | date = February 2019 | pmid = 30208979 | doi = 10.1017/S0029665118001192 }} by creating new iodine-containing epitopes or exposing cryptic epitopes.{{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 }}
• Via thyrocyte damage: Iodine exposure has been shown to increase the level of reactive oxygen species. They enhance the expression of the intracellular adhesion molecule-1 on the thyrocytes, which could attract the immuno-competent cells into the thyroid gland. Iodine also promotes thyrocyte apoptosis.
• Via immune cell behaviour: Iodine has an influence on immune cells.

Comorbid autoimmune diseases are a risk factor for developing Hashimoto's thyroiditis, and the opposite is also true. Another thyroid disease closely associated with Hashimoto's thyroiditis is Graves' disease. Autoimmune diseases affecting other organs most commonly associated with Hashimoto's thyroiditis include celiac disease, type 1 diabetes, vitiligo, alopecia,{{cite book |doi=10.1159/000363162 |chapter=Clinical Aspects of Hashimoto's Thyroiditis |title=Paediatric Thyroidology |series=Endocrine Development |year=2014 | vauthors = Radetti G |volume=26 |pages=158–170 |pmid=25231451 |isbn=978-3-318-02720-4 }} Addison disease, Sjogren's syndrome, and rheumatoid arthritis{{Cite web |title=Hashimoto's Disease |url=https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease |url-status=live |archive-url=https://web.archive.org/web/20211208141910/https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease |archive-date=8 December 2021 |access-date=2023-01-23 |website=National Institute of Diabetes and Digestive and Kidney Diseases |language=en-US}} Autoimmune thyroiditis has also been seen in patients with autoimmune polyendocrine syndromes type 1 and 2.

Other environmental factors include selenium deficiency, infectious diseases such as hepatitis C, rubella, and possibly Covid-19,{{cite journal | vauthors = Saranac L, Zivanovic S, Bjelakovic B, Stamenkovic H, Novak M, Kamenov B | title = Why is the thyroid so prone to autoimmune disease? | journal = Hormone Research in Paediatrics | volume = 75 | issue = 3 | pages = 157–165 | date = 2011 | pmid = 21346360 | doi = 10.1159/000324442 | doi-access = free }}{{cite journal | vauthors = Lambert N, Strebel P, Orenstein W, Icenogle J, Poland GA | title = Rubella | language = English | journal = Lancet | volume = 385 | issue = 9984 | pages = 2297–2307 | date = June 2015 | pmid = 25576992 | pmc = 4514442 | doi = 10.1016/S0140-6736(14)60539-0 }}{{cite journal | vauthors = Lui DT, Lee CH, Woo YC, Hung IF, Lam KS | title = Thyroid dysfunction in COVID-19 | journal = Nature Reviews. Endocrinology | volume = 20 | issue = 6 | pages = 336–348 | date = June 2024 | pmid = 38347167 | doi = 10.1038/s41574-023-00946-w }} toxins, dietary factors, radiation exposure, and gut dysbiosis.

The pathophysiology of autoimmune thyroiditis is not well understood.{{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}} However, once the disease is established, its core processes have been observed:

Hashimoto's thyroiditis is a T-lymphocyte mediated attack on the thyroid gland. T helper 1 cells trigger macrophages and cytotoxic lymphocytes to destroy thyroid follicular cells, while T helper 2 cells stimulate the excessive production of B cells and plasma cells which generate antibodies against the thyroid antigens, leading to thyroiditis. The three major antibodies are: Thyroid peroxidase Antibodies (TPOAb), Thyroglobulin Antibodies (TgAb), and Thyroid stimulating hormone receptor Antibodies (TRAb), with TPOAb and TgAb being most commonly implicated in Hashimotos. 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. However, they may exacerbate further thyroid destruction by binding the complement system and triggering apoptosis of thyroid cells. TPO antibody levels may correlate with the degree of lymphocyte infiltration of the thyroid.{{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 }}{{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 }}

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.{{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}} Hypothyroidism is caused by replacement of follicular cells with parenchymatous tissue.{{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 }}

Partial regeneration of the thyroid tissue can occur, but this has not been observed to normalise hormonal levels.{{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 }}{{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 }}

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File:Hashimoto thyroiditis -- high mag.jpg

Gross pathology of a thyroid with autoimmune thyroiditis may show an symmetrically enlarged thyroid. It is often paler in color, in comparison to normal thyroid tissue which is reddish-brown.

Microscopic examination (histology) will show lymphocytes (including plasma B-cells) diffusely infiltrating the parenchyma. The lymphocytes are predominately T-lymphocytes with a representation of both CD4+ and CD8+ cells. The plasma cells are polyclonal, with present germinal centers resembling the structure of a lymph node (also called secondary lymphoid follicles, not to be confused with the normally present colloid-filled follicles that constitute the thyroid).

In late stages of the disease, the thyroid may be atrophic. Colloid-filled follicles shrink and the cuboidal cells that usually line the follicles become Hürthle cells. Fibrous tissue may be found throughout the affected thyroid as well. Severe thyroid atrophy presents often with denser fibrotic bands of collagen that remains within the confines of the thyroid capsule.

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. A rare but serious complication is thyroid lymphoma, generally the B-cell type, non-Hodgkin lymphoma.

File:Hashimoto-Thyreoiditis.JPG

Physicians will often start by assessing reported symptoms and performing a thorough physical exam, including a neck exam. Patients may have a "firm, bumpy, symmetric, painless goiter", however, up to 10% of patients may have an atrophied thyroid.

Tests for antibodies against thyroid peroxidase, thyroglobulin, and thyrotropin receptors can detect autoimmune processes against the thyroid. 90% of hashimoto's patients have elevated levels of thyroid peroxidase antibodies. However, seronegative (without circulating autoantibodies) thyroiditis is also possible.{{cite journal | vauthors = Grani G, Carbotta G, Nesca A, D'Alessandri M, Vitale M, Del Sordo M, Fumarola A | title = A comprehensive score to diagnose Hashimoto's thyroiditis: a proposal | journal = Endocrine | volume = 49 | issue = 2 | pages = 361–365 | date = June 2015 | pmid = 25280964 | doi = 10.1007/s12020-014-0441-5 | s2cid = 23026213 }} There may be circulating antibodies before the onset of any symptoms.

File:Hashimoto Thyroiditis.jpg

An ultrasound may be useful in detecting Hashimoto thyroiditis, especially in those with seronegative thyroiditis, or when patients have normal laboratory values but symptoms of autoimmune thyroiditis. Key features detected in the ultrasound of a person with Hashimoto's thyroiditis include "echogenicity, heterogeneity, hypervascularity, and presence of small cysts." Images obtained with ultrasound can evaluate the size of the thyroid, reveal the presence of nodules, or provide clues to the diagnosis of other thyroid conditions.

Nuclear imaging showing thyroid uptake can also be helpful in diagnosing thyroid function, particularly differential diagnosis.

To detect if the pituitary is stimulating an underperforming thyroid to produce more thyroid hormone. Thyroid-stimulating hormone (TSH) secretion from the anterior pituitary increases in response to decreased serum thyroid hormones. If elevated, it signifies hypothyroidism. The elevation is usually a marked increase over the normal range. TSH is the preferred initial test of thyroid function as it has a higher sensitivity to changes in thyroid status than free T₄.{{Cite book | author = Royal College of Pathologists of Australasia | chapter = Thyroid stimulating hormone | chapter-url = https://www.rcpa.edu.au/Manuals/RCPA-Manual/Pathology-Tests/T/Thyroid-stimulating-hormone | title = Royal College of Pathologists of Australasia Manual }}

Biotin can cause this test to read "falsely low". Time of day can affect the results of this test; TSH peaks early in the morning and slumps in the late afternoon to early evening,{{cite journal | vauthors = Ikegami K, Refetoff S, Van Cauter E, Yoshimura T | title = Interconnection between circadian clocks and thyroid function | journal = Nature Reviews. Endocrinology | volume = 15 | issue = 10 | pages = 590–600 | date = October 2019 | pmid = 31406343 | pmc = 7288350 | doi = 10.1038/s41574-019-0237-z }} with "a variation in TSH by a mean of between 0.95 mIU/mL to 2.0 mIU/mL".{{cite journal | vauthors = Sheehan MT | title = Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care | journal = Clinical Medicine & Research | volume = 14 | issue = 2 | pages = 83–92 | date = June 2016 | pmid = 27231117 | pmc = 5321289 | doi = 10.3121/cmr.2016.1309 }} Hypothyroidism is diagnosed more often in samples taken soon after waking.{{cite journal | vauthors = Sviridonova MA, Fadeyev VV, Sych YP, Melnichenko GA | title = Clinical significance of TSH circadian variability in patients with hypothyroidism | journal = Endocrine Research | volume = 38 | issue = 1 | pages = 24–31 | date = 2013-05-01 | pmid = 22857384 | doi = 10.3109/07435800.2012.710696 }}

To detect a lack of thyroid hormones (hypothyroidism), or excess of thyroid hormones (hyperthyroidism). The two thyroid hormones are Thyroxine (T₄) and Tri-iodothyronine (T₃). T₄ and T₃ can be measured by their total amount, or free amount. As the free amount reflects the amount available to body tissues, the most treatment-relevant measures for thyroid disorders are Free T₃ and Free T₄.{{cite journal | vauthors = Welsh KJ, Soldin SJ | title = DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays? | journal = European Journal of Endocrinology | volume = 175 | issue = 6 | pages = R255–R263 | date = December 2016 | pmid = 27737898 | pmc = 5113291 | doi = 10.1530/EJE-16-0193 }} Typically, Free T₄ is the preferred test for hypothyroidism,{{cite journal | vauthors = Van Uytfanghe K, Ehrenkranz J, Halsall D, Hoff K, Loh TP, Spencer CA, Köhrle J | title = Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status | journal = Thyroid | volume = 33 | issue = 9 | pages = 1013–1028 | date = September 2023 | pmid = 37655789 | pmc = 10517335 | doi = 10.1089/thy.2023.0169 }} as Free T₃ immunoassay tests are less reliable at detecting low levels of thyroid hormone,{{Cite book | author = Royal College of Pathologists of Australasia | chapter = Free T3 | chapter-url=https://www.rcpa.edu.au/Manuals/RCPA-Manual/Pathology-Tests/F/Free-T3 | title = Royal College of Pathologists of Australasia Manual}} and they are more susceptible to interference. Free T₄ levels will usually be lowered, but sometimes might be normal.{{Cite web |title=Hashimoto's Thyroiditis |url=https://www.thyroid.org/hashimotos-thyroiditis/ |url-status=live |archive-url=https://web.archive.org/web/20230923182829/http://www.thyroid.org/hashimotos-thyroiditis/ |archive-date=23 September 2023 |access-date=2023-01-23 |website=American Thyroid Association |language=en-US}}

Immunoassay tests of Free T₄ and Free T₃ may overestimate concentrations, particularly at low thyroid hormone levels, which is why results are typically read in conjunction with TSH, a more sensitive measure. LC-MSMS assays are rarer, but they are "highly specific, sensitive, precise, and can detect hormones found in low concentrations."

Muscle biopsy is not necessary for diagnosis of myopathy due to hypothyroid muscle fibre changes, however it may reveal confirmatory features.

There is no cure for Hashimoto's Thyroiditis.{{cite journal | vauthors = Ludgate ME, Masetti G, Soares P | title = The relationship between the gut microbiota and thyroid disorders | journal = Nature Reviews. Endocrinology | volume = 20 | issue = 9 | pages = 511–525 | date = September 2024 | pmid = 38906998 | doi = 10.1038/s41574-024-01003-w }}{{Cite web | author = Healthdirect Australia |date=2023-02-03 |title=Hashimoto's disease |url=https://www.healthdirect.gov.au/hashimotos-disease |access-date=2024-12-05 |website=www.healthdirect.gov.au |language=en-AU}} There is currently no known way to stop auto-immune lymphocytes infiltrating the thyroid or to stimulate regeneration of thyroid tissue. However, the condition can be managed.

File:T4 LT4 LT4 Sodium - T3 LT3 LT3 Sodium.png

Hypothyroidism caused by Hashimoto's thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine (LT₄), liothyronine (LT₃), or desiccated thyroid extract (T₄+T₃). In most cases, the treatment needs to be taken for the rest of the person's life.

The standard of care is levothyroxine (LT₄) therapy, which is an oral medication identical in molecular structure to endogenous thyroxine (T₄). Levothyroxine sodium has a sodium salt added to increase the gastrointestinal absorption of levothyroxine.{{Cite book | vauthors = Wiersinga WM |title=Endocrinology: Adult and Pediatric |year=2016 |edition=7th |volume=2 |pages=1540–1556}} Levothyroxine has the benefits of a long half-life{{cite journal |vauthors=Groenewegen KL, Mooij CF, van Trotsenburg AS |date=2021 |title=Persisting symptoms in patients with Hashimoto's disease despite normal thyroid hormone levels: Does thyroid autoimmunity play a role? A systematic review |journal=Journal of Translational Autoimmunity |volume=4 |pages=100101 |doi=10.1016/j.jtauto.2021.100101 |pmc=8122172 |pmid=34027377}} leading to stable thyroid hormone levels,{{cite journal | vauthors = McAninch EA, Bianco AC | title = The Swinging Pendulum in Treatment for Hypothyroidism: From (and Toward?) Combination Therapy | language = English | journal = Frontiers in Endocrinology | volume = 10 | pages = 446 | date = 2019-07-09 | pmid = 31354624 | pmc = 6629976 | doi = 10.3389/fendo.2019.00446 | doi-access = free }} ease of monitoring, excellent safety{{cite book | vauthors = Brown DC | chapter = Chapter 37 - Thyroid hormones, antithyroid drugs |date=2012-01-01 | title = Clinical Pharmacology | edition = Eleventh |pages=587–595 | veditors = Bennett PN, Brown MJ, Sharma P |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780702040849000768 |access-date=2024-12-05 |place=Oxford |publisher=Churchill Livingstone | doi = 10.1016/B978-0-7020-4084-9.00076-8 |isbn=978-0-7020-4084-9 }} and efficacy record, and usefulness in pregnancy as it can cross the fetal blood-brain barrier.

Levothyroxine dosing to normalise TSH is based on the amount of residual endogenous thyroid function and the patient’s weight, particularly lean body mass. The dose can be adjusted based upon each patient, for example, the dose may be lowered for elderly patients or patients with certain cardiac conditions, but is increased in pregnant patients. It is administered on a consistent schedule. Levothyroxine may be dosed daily or weekly, however weekly dosing may be associated with higher TSH levels, elevated thyroid hormone levels, and transient "echocardiographic changes in some patients following 2-4 h of thyroxine intake".{{cite journal | vauthors = Chiu HH, Larrazabal R, Uy AB, Jimeno C | title = Weekly Versus Daily Levothyroxine Tablet Replacement in Adults with Hypothyroidism: A Meta-Analysis | journal = Journal of the ASEAN Federation of Endocrine Societies | volume = 36 | issue = 2 | pages = 156–160 | date = 2021 | pmid = 34966199 | pmc = 8666497 | doi = 10.15605/jafes.036.02.07 }}{{cite journal | vauthors = Dutta D, Jindal R, Kumar M, Mehta D, Dhall A, Sharma M | title = Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis | language = en-US | journal = Indian Journal of Endocrinology and Metabolism | volume = 25 | issue = 2 | pages = 76–85 | date = March–April 2021 | pmid = 34660234 | pmc = 8477739 | doi = 10.4103/ijem.IJEM_789_20 | doi-access = free }}

Some patients elect combination therapy with both levothyroxine and liothyronine (which is identical in molecular structure to tri-iodothyronine) however studies of combination therapy are limited, and five meta-analyses/reviews "suggested no clear advantage of the combination therapy." However, subgroup analysis found that patients who remain the most symptomatic while taking levothyroxine may benefit from therapy containing liothyronine.

There is a lack of evidence around the benefits, long-term effects and side effects of desiccated thyroid extract. It is no longer recommended for the treatment of hypothyroidism.{{cite journal | vauthors = Riis KR, Larsen CB, Bonnema SJ | title = Potential Risks and Benefits of Desiccated Thyroid Extract for the Treatment of Hypothyroidism: A Systematic Review | journal = Thyroid | volume = 34 | issue = 6 | pages = 687–701 | date = June 2024 | pmid = 38526391 | doi = 10.1089/thy.2023.0649 | url = https://findresearcher.sdu.dk/ws/files/265931781/RiisManuscript_clean.pdf }}

Side effects of thyroid replacement therapy are associated with "inadequate or excessive doses." Symptoms to watch for include, but are not limited to, anxiety, tremor, weight loss, heat sensitivity, diarrhea, and shortness of breath. More worrisome symptoms include atrial fibrillation and bone density loss. Long term over-treatment is associated with increased mortality and dementia.

Thyroid Stimulating Hormone (TSH) is the laboratory value of choice for monitoring response to treatment with levothyroxine. When treatment is first initiated, TSH levels may be monitored as often as a frequency of every 6–8 weeks. Each time the dose is adjusted, TSH levels may be measured at that frequency until the correct dose is determined. Once titrated to a proper dose, TSH levels will be monitored yearly. The target level for TSH is the subject of debate, with factors like age, sex, individual needs and special circumstances such as pregnancy being considered. Recent studies suggest that adjusting therapy based on thyroid hormone levels (T₄ and/or T₃) may be important.

Monitoring liothyronine treatment or combination treatment can be challenging.{{Citation |title=Thyroid hormones |date=2006-01-01 |pages=3409–3416 | veditors = Aronson JK |url=https://www.sciencedirect.com/science/article/abs/pii/B0444510052009773 |access-date=2024-12-05 |place=Amsterdam |publisher=Elsevier |doi=10.1016/B0-44-451005-2/00977-3 |isbn=978-0-444-51005-1 |encyclopedia=Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions (Fifteenth Edition)}} Liothyronine can suppress TSH to a greater extent than levothyroxine.{{Cite journal | vauthors = Taylor P, Arooj A, Hanna S, Eligar V, Muhammad Z, Stedman M, Premawardhana L, Okosieme O, Heald A, Dayan C |date=2023-10-31 |title=Thyroid hormone profiles on non-standard thyroid hormone replacement |url=https://www.endocrine-abstracts.org/ea/0094/ea0094p128 |journal=Endocrine Abstracts |language=en |publisher=Bioscientifica |volume=94 |doi=10.1530/endoabs.94.P128}} Short-acting Liothyronine's short half-life can result in large fluctuations of free T₃ over the course of 24 hours.{{cite journal | vauthors = Saravanan P, Siddique H, Simmons DJ, Greenwood R, Dayan CM | title = Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 115 | issue = 4 | pages = 261–267 | date = April 2007 | pmid = 17479444 | doi = 10.1055/s-2007-973071 }}

Patients may have to adjust their dosage several times over the course of the disease. Endogenous thyroid hormone levels may fluctuate, particularly early in the disease.{{cite journal | vauthors = Dunne C, De Luca F | title = Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent Hyperthyroidism in the Absence of TSH Receptor Antibodies | journal = Case Reports in Endocrinology | volume = 2014 | issue = 1 | pages = 749576 | date = 2014 | pmid = 25114812 | pmc = 4119923 | doi = 10.1155/2014/749576 | doi-access = free }} Patients may sometimes develop hyperthyroidism, even after long-term treatment. This can be due to a number of factors including acute attacks of destructive thyrotoxicosis (autoimmune attacks on the thyroid resulting in rises in thyroid hormone levels as thyroid hormones leak out of the damaged tissues). This is usually followed by hypothyroidism.

Measuring reverse tri-iodothyronine (rT₃) is often mentioned in the lay (non-medical) press as a possible marker to inform T₄ or T₃ therapy, "however, there is currently no evidence to support this application" as of 2023. Although cited in the lay press as a possible competitor to T₃, it is unlikely that rT₃ causes hypothyroid symptoms by out-competing T₃ for thyroid hormone receptors, as it has a binding affinity 200 times weaker. It is also unlikely that rT₃ causes poor T₄ to T₃ conversion; despite being demonstrated in vivo to have the potential to inhibit DIO-mediated T₄ to T₃ conversion, this is considered improbable at normal body hormone concentrations.{{cite journal | vauthors = Halsall DJ, Oddy S | title = Clinical and laboratory aspects of 3,3',5'-triiodothyronine (reverse T3) | journal = Annals of Clinical Biochemistry | volume = 58 | issue = 1 | pages = 29–37 | date = January 2021 | pmid = 33040575 | doi = 10.1177/0004563220969150 }}

Multiple studies have demonstrated persistent symptoms in Hashimoto's patients with normal thyroid hormone levels (euthyroid){{cite journal | vauthors = Taylor PN, Medici MM, Hubalewska-Dydejczyk A, Boelaert K | title = Hypothyroidism | journal = Lancet | volume = 404 | issue = 10460 | pages = 1347–1364 | date = October 2024 | pmid = 39368843 | doi = 10.1016/S0140-6736(24)01614-3 }} and an estimated 10%-15% of patients treated with levothyroxine monotherapy are dissatisfied due to persistent symptoms of hypothyroidism.{{cite journal | vauthors = Jonklaas J, Razvi S | title = Reference intervals in the diagnosis of thyroid dysfunction: treating patients not numbers | journal = The Lancet. Diabetes & Endocrinology | volume = 7 | issue = 6 | pages = 473–483 | date = June 2019 | pmid = 30797750 | doi = 10.1016/S2213-8587(18)30371-1 }}{{cite journal | vauthors = Hegedüs L, Bianco AC, Jonklaas J, Pearce SH, Weetman AP, Perros P | title = Primary hypothyroidism and quality of life | journal = Nature Reviews. Endocrinology | volume = 18 | issue = 4 | pages = 230–242 | date = April 2022 | pmid = 35042968 | pmc = 8930682 | doi = 10.1038/s41574-021-00625-8 }} Several different hypothesised causes are discussed in the medical literature:

Peripheral tissue T₄ to T₃ conversion may be inadequate: Some patients on LT₄ monotherapy may have blood T₃ levels low or below the normal range, and/or may have local T₃ deficiency in some tissues.{{cite journal |vauthors=Wiersinga WM |date=March 2014 |title=Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism |journal=Nature Reviews. Endocrinology |volume=10 |issue=3 |pages=164–174 |doi=10.1038/nrendo.2013.258 |pmid=24419358}} Although both molecules can have biological effects, thyroxine (T₄) is considered the "storage form" of thyroid hormone with much less effect, while tri-iodothyronine (T₃) is considered the active form used by body tissues.{{cite journal | vauthors = Morris JC, Galton VA | title = The isolation of thyroxine (T4), the discovery of 3,5,3'-triiodothyronine (T3), and the identification of the deiodinases that generate T3 from T4: An historical review | journal = Endocrine | volume = 66 | issue = 1 | pages = 3–9 | date = October 2019 | pmid = 31256344 | doi = 10.1007/s12020-019-01990-1 }}{{cite journal | vauthors = Abdalla SM, Bianco AC | title = Defending plasma T3 is a biological priority | journal = Clinical Endocrinology | volume = 81 | issue = 5 | pages = 633–641 | date = November 2014 | pmid = 25040645 | pmc = 4699302 | doi = 10.1111/cen.12538 }} Thus the body must convert thyroxine into tri-iodothyronine. Tri-iodothyronine is produced primarily by conversion in the liver, kidney, skeletal muscle and pituitary gland.{{cite journal | vauthors = Danzi S, Klein I | title = Thyroid hormone and the cardiovascular system | journal = The Medical Clinics of North America | volume = 96 | issue = 2 | pages = 257–268 | date = March 2012 | pmid = 22443974 | doi = 10.1016/j.mcna.2012.01.006 | series = Thyroid Disorders and Diseases }}

Adequate conversion requires sufficient levels of the micronutrients zinc,{{cite journal | vauthors = Knezevic J, Starchl C, Tmava Berisha A, Amrein K | title = Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function? | journal = Nutrients | volume = 12 | issue = 6 | pages = 1769 | date = June 2020 | pmid = 32545596 | pmc = 7353203 | doi = 10.3390/nu12061769 | doi-access = free }} selenium, iron,{{Cite journal | vauthors = Ghiya R, Ahmad S |date=2019-04-30 |title=SUN-591 Severe Iron-Deficiency Anemia Leading to Hypothyroidism |journal=Journal of the Endocrine Society|volume=3 |issue=Suppl 1 |pages=SUN-591 |doi=10.1210/js.2019-SUN-591 |doi-access=free |pmc=6552785 }} and possibly vitamin A.{{cite journal |vauthors=Capriello S, Stramazzo I, Bagaglini MF, Brusca N, Virili C, Centanni M |title=The relationship between thyroid disorders and vitamin A.: A narrative minireview |journal=Frontiers in Endocrinology |volume=13 |pages=968215 |date=2022-10-11 |pmid=36303869 |pmc=9592814 |doi=10.3389/fendo.2022.968215 |doi-access=free}} Conversion rates may decline with age.{{cite journal | vauthors = Strich D, Karavani G, Edri S, Gillis D | title = TSH enhancement of FT4 to FT3 conversion is age dependent | journal = European Journal of Endocrinology | volume = 175 | issue = 1 | pages = 49–54 | date = July 2016 | pmid = 27150496 | doi = 10.1530/EJE-16-0007 }} Since deiodinase type 2 is necessary for T₄ to T₃ conversion in some peripheral tissues, "patients with DIO2 gene polymorphisms may have variable peripheral T₃ availability", leading to localised hypothyroidism in some tissues. The Thr92Ala DIO2 polymorphism is present in 12–36% of the population.

For the latter patients, levothyroxine monotherapy may not be sufficient and patients may have improvement on combination therapy of T₄ and T₃.{{Cite journal | vauthors = Veríssimo D, Reis A, Monteiro M, Dias L |date=2020-08-21 |title=When levothyroxine is not enough- combination therapy with liothyronine |url=https://www.endocrine-abstracts.org/ea/0070/ea0070ep451 |journal=Endocrine Abstracts |language=en |publisher=Bioscientifica |volume=70 |doi=10.1530/endoabs.70.EP451}} As standard immunoassay tests can overestimate blood T₄ and T₃ levels, Ultrafiltration LC-MSMS T₄ and T₃ tests may help to identify patients who would benefit from additional T₃.

There is ongoing debate about how to define euthyroidism and whether TSH is its best indicator. TSH may be useful to detect poor thyroid output and may reflect the state of thyroid hormones in the hypothalamic-pituitary-thyroid axis, but not the presence of hormones in other body tissues. As a result, LT₄ monotherapy may not result in a "truly biochemically euthyroid state." Patients may express a preference for "low normal or below normal TSH values" and/or T₄ and T₃ monitoring. The monitoring of other biomarkers that reflect the action of thyroid hormone on tissues has also been proposed.{{cite journal | vauthors = McAninch EA, Rajan KB, Miller CH, Bianco AC | title = Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 103 | issue = 12 | pages = 4533–4542 | date = August 2018 | pmid = 30124904 | pmc = 6226605 | doi = 10.1210/jc.2018-01361 }}

As immunoassay Free T₃ and Free T4 tests can overestimate levels, particularly at low thyroid hormone levels, hypothyroidism may be undertreated. LC-MSMS tests may provide more reliable measures.

It is hypothesised that autoimmunity may play some role in euthyroid symptoms. Hypothesised mechanisms include the proposal that TPO-antibody-producing lymphocytes may travel out of the thyroid to other tissue, creating symptoms and inflammation due to cross-reaction,{{cite journal | vauthors = Guldvog I, Reitsma LC, Johnsen L, Lauzike A, Gibbs C, Carlsen E, Lende TH, Narvestad JK, Omdal R, Kvaløy JT, Hoff G, Bernklev T, Søiland H | title = Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial | journal = Annals of Internal Medicine | volume = 170 | issue = 7 | pages = 453–464 | date = April 2019 | pmid = 30856652 | doi = 10.7326/M18-0284 }} or "the inflammatory nature of [...] persistently increased circulating cytokine levels." Multiple studies find that antibodies coincide with symptoms even in euthyroid patients, and higher levels are associated with increased symptoms, however "the found association does not prove a causality". No treatment currently exists for Hashimoto's autoimmunity, although observed wellbeing improvements after surgical thyroid removal are hypothesised to be due to removing the autoimmune stimulus.

It is hypothesised that euthyroid symptoms may not be due to Hashimoto's or hypothyroidism, but some other "physical and psychosocial co-morbidities".

Some patients may perceive improved wellbeing while in thyrotoxicosis, however overtreatment has risks (known risks for levothyroxine and unknown risks for liothyronine). One study demonstrated surgical thyroid removal may substantially improve fatigue and wellbeing, see Surgery considerations, below.

It is not established that reducing antithyroid antibodies in Hashimoto's has benefits.{{cite journal | vauthors = Chaker L, Razvi S, Bensenor IM, Azizi F, Pearce EN, Peeters RP | title = Hypothyroidism | journal = Nature Reviews. Disease Primers | volume = 8 | issue = 1 | pages = 30 | date = May 2022 | pmid = 35589725 | pmc = 6619426 | doi = 10.1038/s41572-022-00357-7 }}{{cite journal | vauthors = Wichman J, Winther KH, Bonnema SJ, Hegedüs L | title = Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis | journal = Thyroid | volume = 26 | issue = 12 | pages = 1681–1692 | date = December 2016 | pmid = 27702392 | doi = 10.1089/thy.2016.0256 }} A systematic review and meta-analysis of selenium trials found that while selenium reduces TPO antibodies, there was a lack of evidence of effects on "disease remission, progression, lowered levothyroxine dose or improved quality of life".

Selenium,{{cite journal | vauthors = Huwiler VV, Maissen-Abgottspon S, Stanga Z, Mühlebach S, Trepp R, Bally L, Bano A | title = Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials | journal = Thyroid | volume = 34 | issue = 3 | pages = 295–313 | date = March 2024 | pmid = 38243784 | pmc = 10951571 | doi = 10.1089/thy.2023.0556 }} vitamin D,{{cite journal | vauthors = Jiang H, Chen X, Qian X, Shao S | title = Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis-A meta-analysis of randomized controlled trials | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 47 | issue = 6 | pages = 767–775 | date = June 2022 | pmid = 34981556 | pmc = 9302126 | doi = 10.1111/jcpt.13605 }} and metformin{{cite journal | vauthors = Jia X, Zhai T, Zhang JA | title = Metformin reduces autoimmune antibody levels in patients with Hashimoto's thyroiditis: A systematic review and meta-analysis | journal = Autoimmunity | volume = 53 | issue = 6 | pages = 353–361 | date = September 2020 | pmid = 32741222 | doi = 10.1080/08916934.2020.1789969 }} can reduce thyroid peroxidase antibodies. There is preliminary evidence that levothyroxine,{{cite journal | vauthors = Aksoy DY, Kerimoglu U, Okur H, Canpinar H, Karaağaoğlu E, Yetgin S, Kansu E, Gedik O | title = Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto's thyroiditis | journal = Endocrine Journal | volume = 52 | issue = 3 | pages = 337–343 | date = June 2005 | pmid = 16006728 | doi = 10.1507/endocrj.52.337 }}{{cite journal | vauthors = Padberg S, Heller K, Usadel KH, Schumm-Draeger PM | title = One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients with levothyroxine: is there a benefit? | journal = Thyroid | volume = 11 | issue = 3 | pages = 249–255 | date = March 2001 | pmid = 11327616 | doi = 10.1089/105072501750159651 }} {{Needs update|date=February 2025|reason=Articles are from the very early 2000s.}}aloe vera juice{{cite journal | vauthors = Metro D, Cernaro V, Papa M, Benvenga S | title = Marked improvement of thyroid function and autoimmunity by Aloe barbadensis miller juice in patients with subclinical hypothyroidism | journal = Journal of Clinical & Translational Endocrinology | volume = 11 | pages = 18–25 | date = March 2018 | pmid = 29527506 | pmc = 5842288 | doi = 10.1016/j.jcte.2018.01.003 }} and black cumin seed{{cite journal | vauthors = Osowiecka K, Myszkowska-Ryciak J | title = The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review | journal = Nutrients | volume = 15 | issue = 4 | pages = 1041 | date = February 2023 | pmid = 36839399 | pmc = 9962371 | doi = 10.3390/nu15041041 | doi-access = free }} may reduce thyroid peroxidase antibodies. Metformin can reduce thyroglobulin antibodies. It is not established that a gluten-free diet can reduce antibodies when there is no comorbid coeliac disease.{{cite journal | vauthors = Szczuko M, Syrenicz A, Szymkowiak K, Przybylska A, Szczuko U, Pobłocki J, Kulpa D | title = Doubtful Justification of the Gluten-Free Diet in the Course of Hashimoto's Disease | journal = Nutrients | volume = 14 | issue = 9 | pages = 1727 | date = April 2022 | pmid = 35565695 | pmc = 9101474 | doi = 10.3390/nu14091727 | doi-access = free }} Gluten-free diets have been shown in several studies to reduce antibodies, and in other studies to have no effect, however there were significant confounding issues in these studies, including not ruling out comorbid coeliac disease.

One study found surgical thyroid removal can substantially reduce anti-thyroid antibody levels, see Surgery considerations, below.

Surgery is not the initial treatment of choice for autoimmune disease, and uncomplicated Hashimoto's thyroiditis is not an indication for thyroidectomy. Patients generally may discuss surgery with their doctor if they are experiencing significant pressure symptoms, or cosmetic concerns, or have nodules present on ultrasound. One well-conducted study of patients with troublesome general symptoms and with anti-thyroperoxidase (anti-TPO) levels greater than 1000 IU/ml (normal <100 IU/ml) showed that total thyroidectomy caused the symptoms to resolve and median anti-thyroid peroxidase levels to reduce from 2232 to 152 IU/mL,{{Cite web | vauthors = Garber M |date=2019-08-12 |title=Is there a role for surgery in treating Hashimoto's thyroiditis? |url=https://www.health.harvard.edu/blog/is-there-a-role-for-surgery-in-treating-hashimotos-thyroiditis-2019081217443 |access-date=2024-12-05 |website=Harvard Health |language=en}} but post-operative complications were higher than expected: infection (4.1%), permanent hypoparathyroidism (4.1%) and recurrent laryngeal nerve injury (5.5%).{{cite journal | vauthors = Perros P, Van Der Feltz-Cornelis C, Papini E, Nagy EV, Weetman AP, Hegedüs L | title = The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review | journal = Clinical Endocrinology | volume = 98 | issue = 4 | pages = 461–468 | date = April 2023 | pmid = 33783849 | doi = 10.1111/cen.14473 }}

Zinc may increase free T₃ levels. A small pilot study found Ashwagandha Root may increase T₃ and T4 levels, however, there's a lack of strong evidence of this benefit and Ashwagandha has a potential to cause adrenal insufficiency.

As of 2022, there has been only one study of low-dose naltrexone in Hashimoto's, which did not demonstrate efficacy, therefore nothing supports its use; Removing dairy products in those without lactose intolerance has not been found to be supported.{{cite journal | vauthors = Larsen D, Singh S, Brito M | title = Thyroid, Diet, and Alternative Approaches | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 107 | issue = 11 | pages = 2973–2981 | date = November 2022 | pmid = 35952387 | doi = 10.1210/clinem/dgac473 }} While soy isoflavones have the potential to theoretically affect T₃ and T₄ production, studies in those with sufficient iodine find no effect.

Overt, symptomatic thyroid dysfunction is the most common complication, with about 5% of people with subclinical hypothyroidism and chronic autoimmune thyroiditis progressing to thyroid failure every year. Transient periods of thyrotoxicosis (over-activity of the thyroid) sometimes occur, and rarely the illness may progress to full hyperthyroid Graves' disease with active orbitopathy (bulging, inflamed eyes).{{Cite book | vauthors = Monaco F |title=Thyroid Diseases |date=2012 |publisher=CRC Press |isbn=978-1-4398-6839-3 |location=Hoboken |pages=77–97}}

Rare cases of fibrous autoimmune thyroiditis present with severe shortness of breath and difficulty swallowing, resembling aggressive thyroid tumors, but such symptoms always improve with surgery or corticosteroid therapy. Although primary thyroid B-cell lymphoma affects fewer than one in 1000 persons, it is more likely to affect those with long-standing autoimmune thyroiditis, as there is a 67- to 80-fold increased risk of developing primary thyroid lymphoma in patients with Hashimoto's thyroiditis.{{cite journal | vauthors = Noureldine SI, Tufano RP | title = Association of Hashimoto's thyroiditis and thyroid cancer | language = en-US | journal = Current Opinion in Oncology | volume = 27 | issue = 1 | pages = 21–25 | date = January 2015 | pmid = 25390557 | doi = 10.1097/CCO.0000000000000150 | s2cid = 32109200 }}

Myopathy as a result of muscle fibre changes due to thyroid hormone deficiency may take months or years of thyroid hormone treatment to resolve.{{cite journal | vauthors = Winter S, Heiling B, Eckardt N, Kloos C, Axer H | title = Hoffmann's syndrome in the differential work-up of myopathic complaints: a case report | journal = Journal of Medical Case Reports | volume = 17 | issue = 1 | pages = 473 | date = October 2023 | pmid = 37907975 | pmc = 10617199 | doi = 10.1186/s13256-023-04184-6 | doi-access = free }}

Thyroid peroxidase antibodies typically (but not always) decline in patients treated with levothyroxine, with decreases varying between 10% and 90% after a follow-up of 6 to 24 months.{{cite journal | vauthors = Schmidt M, Voell M, Rahlff I, Dietlein M, Kobe C, Faust M, Schicha H | title = Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto's thyroiditis) treated with levothyroxine | journal = Thyroid | volume = 18 | issue = 7 | pages = 755–760 | date = July 2008 | pmid = 18631004 | doi = 10.1089/thy.2008.0008 }} One study of patients treated with levothyroxine observed that 35 out of 38 patients (92%) had declines in thyroid peroxidase antibody levels over five years, lowering by 70% on average. 6 of the 38 patients (16%) had thyroid peroxidase antibody levels return to normal.

Many children diagnosed with Hashimoto's disease will experience the same progressive course of the disease that adults do.{{cite journal | vauthors = De Luca F, Santucci S, Corica D, Pitrolo E, Romeo M, Aversa T | title = Hashimoto's thyroiditis in childhood: presentation modes and evolution over time | journal = Italian Journal of Pediatrics | volume = 39 | issue = 1 | pages = 8 | date = January 2013 | pmid = 23363471 | pmc = 3567976 | doi = 10.1186/1824-7288-39-8 | doi-access = free }} However, of children who develop anti-thyroid antibodies and hypothyroidism, up to 50% are later observed to have normal antibodies and thyroid hormone levels. One case of true remission has been observed in a 12-year-old girl. Her thyroid was observed via ultrasound to progress from early inflammation to severe end-stage Hashimoto's thyroiditis with hypothyroidism, and then return to "almost normal with only minimal features of inflammation" and euthyroidism.{{cite journal | vauthors = Wu G, Zou D, Cai H, Liu Y | title = Ultrasonography in the diagnosis of Hashimoto's thyroiditis | journal = Frontiers in Bioscience | volume = 21 | issue = 5 | pages = 1006–1012 | date = June 2016 | pmid = 27100487 | doi = 10.2741/4437 }}

Hashimoto's Disease is estimated to affect 2% of the world's population.{{cite journal | vauthors = Chistiakov DA | title = Immunogenetics of Hashimoto's thyroiditis | journal = Journal of Autoimmune Diseases | volume = 2 | issue = 1 | pages = 1 | date = March 2005 | pmid = 15762980 | pmc = 555850 | doi = 10.1186/1740-2557-2-1 | doi-access = free }} About 1.0 to 1.5 in 1000 people have this disease at any time.

Anyone may develop this disease, but it occurs between 8 and 15 times more often in women than in men. Some research suggests a connection to the role of the placenta as an explanation for the sex difference.{{cite journal | vauthors = Natri H, Garcia AR, Buetow KH, Trumble BC, Wilson MA | title = The Pregnancy Pickle: Evolved Immune Compensation Due to Pregnancy Underlies Sex Differences in Human Diseases | journal = Trends in Genetics | volume = 35 | issue = 7 | pages = 478–488 | date = July 2019 | pmid = 31200807 | pmc = 6611699 | doi = 10.1016/j.tig.2019.04.008 }} Other research suggests the difference in prevalence amongst genders is due to the effects of sex hormones.

Autoimmune thyroiditis has a higher prevalence in societies that have a higher intake of iodine in their diet, such as the United States and Japan, and among people who are genetically susceptible.{{cite book |title=Thyroid Diseases |vauthors=Monaco F |publisher=Taylor and Francis |year=2012 |isbn=978-1-4398-6839-3 |page=78}} It is the most common cause of hypothyroidism in areas of sufficient iodine. Also, the rate of lymphocytic infiltration increased in areas where the iodine intake was once low, but increased due to iodine supplementation.{{cite journal | vauthors = Khattak RM, Ittermann T, Nauck M, Below H, Völzke H | title = Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany | journal = Population Health Metrics | volume = 14 | pages = 39 | date = 2016 | pmid = 27833458 | pmc = 5101821 | doi = 10.1186/s12963-016-0111-3 | doi-access = free }}

Iodine deficiency disorder is combated using an increase in iodine in a person's diet. When a dramatic change occurs in a person's diet, they become more at-risk of developing hypothyroidism and other thyroid disorders. Treating iodine deficiency disorder with high salt intakes should be done carefully and cautiously as risk for Hashimoto's may increase.

Geography plays a large role in which regions have access to diets with low or high iodine. Iodine levels in both water and salt should be heavily monitored in order to protect at-risk populations from developing hypothyroidism.{{cite journal | vauthors = Katagiri R, Yuan X, Kobayashi S, Sasaki S | title = Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies | journal = PLOS ONE | volume = 12 | issue = 3 | pages = e0173722 | date = 2017-03-10 | pmid = 28282437 | pmc = 5345857 | doi = 10.1371/journal.pone.0173722 | bibcode = 2017PLoSO..1273722K | doi-access = free }} Geographic trends of hypothyroidism vary across the world as different places have different ways of defining disease and reporting cases. Populations that are spread out or defined poorly may skew data in unexpected ways.

Hashimoto's thyroiditis may affect up to 5% of the United States' population.{{Cite book | vauthors = Biddinger PW |title=Diagnostic Pathology and Molecular Genetics of the Thyroid: A Comprehensive Guide for Practicing Thyroid Pathology |publisher=Lippincott Williams & Wilkins |year=2020 |isbn=978-1-4963-9653-2 |edition=3rd |location=Philadelphia, PA |pages=59–72}} Hashimoto's thyroiditis disorder is thought to be the most common cause of primary hypothyroidism in North America.

Hashimoto's thyroiditis can occur at any age, including children, but more commonly appears in middle age, particularly for men.{{cite web |date=16 July 2012 |title=Hashimoto's disease fact sheet |url=http://www.womenshealth.gov/publications/our-publications/fact-sheet/hashimoto-disease.html |url-status=live |archive-url=https://web.archive.org/web/20141202154021/http://www.womenshealth.gov/publications/our-publications/fact-sheet/hashimoto-disease.html |archive-date=2 December 2014 |access-date=23 November 2014 |publisher=Office on Women's Health, U.S. Department of Health and Human Services, womenshealth.gov (or girlshealth.gov)}} Incidence peaks in the fifth decade of life, but patients are usually diagnosed between age 30–50. The highest prevalence from one study was found in the elderly members of the community.{{cite journal | vauthors = Vanderpump MP | title = The epidemiology of thyroid disease | journal = British Medical Bulletin | volume = 99 | issue = 1 | pages = 39–51 | date = 2011-09-01 | pmid = 21893493 | doi = 10.1093/bmb/ldr030 }} It has been shown that the prevalence of positive tests for thyroid antibodies increases with age, "with a frequency as high as 33 percent in women 70 years old or older."

The prevalence of Hashimoto's varies geographically. The highest rate is in Africa, and the lowest in Asia.{{cite journal | vauthors = Hu X, Chen Y, Shen Y, Tian R, Sheng Y, Que H | title = Global prevalence and epidemiological trends of Hashimoto's thyroiditis in adults: A systematic review and meta-analysis | journal = Frontiers in Public Health | volume = 10 | issue = | pages = 1020709 | date = 2022 | pmid = 36311599 | pmc = 9608544 | doi = 10.3389/fpubh.2022.1020709 | doi-access = free }} In the US, the African-American population experiences it less commonly but has greater associated mortality.{{cite news | vauthors = Boyles S |title=Hypothyroidism Hikes Death Risk in Blacks |url=https://www.medpagetoday.org/endocrinology/thyroid/39357 |work=MedPage Today |date=23 May 2013 }}

Those that already have an autoimmune disease are at greater risk of developing Hashimoto's as the diseases generally coexist with each other. See Causes > Comorbidities, above.

The secular trends of hypothyroidism reveal how the disease has changed over the course of time given changes in technology and treatment options. Even though ultrasound technology and treatment options have improved, the incidence of hypothyroidism has increased according to data focused on the US and Europe. Between 1993 and 2001, per 1000 women, the disease was found varying between 3.9 and 4.89. Between 1994 and 2001, per 1000 men, the disease increased from 0.65 to 1.01.

Also known as Hashimoto's disease, Hashimoto's thyroiditis is named after Japanese physician Hakaru Hashimoto (1881−1934) of the medical school at Kyushu University,{{WhoNamedIt|doctor|1974|Hakaru Hashimoto}} who first described the symptoms of persons with struma lymphomatosa, an intense infiltration of lymphocytes within the thyroid, in 1912 in the German journal called {{Lang|de|Archiv für Klinische Chirurgie}}.{{cite journal |id={{NAID|10005555208}} | vauthors = Hashimoto H |title=Zur Kenntnis der lymphomatösen Veränderung der Schilddrüse (Struma lymphomatosa) |trans-title=Knowledge of lymphomatous changes in the thyroid gland (goiter lymphomatosa) |language=de |journal=Archiv für Klinische Chirurgie |year=1912 |volume=97 |pages=219–248 }} This paper was made up of 30 pages and 5 illustrations all describing the histological changes in the thyroid tissue. Furthermore, all results in his first study were collected from four women. These results explained the pathological characteristics observed in these women especially the infiltration of lymphocyte and plasma cells as well as the formation of lymphoid follicles with germinal centers, fibrosis, degenerated thyroid epithelial cells and leukocytes in the lumen. He described these traits to be histologically similar to those of Mikulic's disease. As mentioned above, once he discovered these traits in this new disease, he named the disease struma lymphomatosa. This disease emphasized the lymphocyte infiltration and formation of the lymphoid follicles with germinal centers, neither of which had ever been previously reported.

Despite Dr. Hashimoto's discovery and publication, the disease was not recognized as distinct from Reidel's thyroiditis, which was a common disease at that time in Europe. Although many other articles were reported and published by other researchers, Hashimoto's struma lymphomatosa was only recognized as an early phase of Reidel's thyroiditis in the early 1900s. It was not until 1931 that the disease was recognized as a disease in its own right, when researchers Allen Graham et al. from Cleveland reported its symptoms and presentation in the same detailed manner as Hashimoto.

In 1956, Drs. Rose and Witebsky were able to demonstrate how immunization of certain rodents with extracts of other rodents' thyroid resembled the disease Hakaru and other researchers were trying to describe. These doctors were also able to describe anti-thyroglobulin antibodies in blood serum samples from these same animals.

Later on in the same year, researchers from the Middlesex Hospital in London were able to perform human experiments on patients who presented with similar symptoms. They purified anti-thyroglobulin antibody from their serum and were able to conclude that these sick patients had an immunological reaction to human thyroglobulin. From this data, it was proposed that Hashimoto's struma could be an autoimmune disease of the thyroid gland: "Following these discoveries, the concept of organ-specific autoimmune disease was established and HT recognized as one such disease."

Following this recognition, the same researchers from Middlesex Hospital published an article in 1962 in The Lancet that included a portrait of Hakaru Hashimoto. The disease became more well known from that moment, and Hashimoto's disease started to appear more frequently in textbooks.{{Cite web |title=Google Books Ngram Viewer |url=https://books.google.com/ngrams/graph?content=hashimoto's+disease&year_start=1800&year_end=2022&corpus=en&smoothing=0&case_insensitive=true |access-date=2024-12-01 |website=books.google.com |language=en}}

It is recommended that hypothyroidism be treated with levothyoxine before conception, to prevent adverse effects on the course of the pregnancy and on the development of the child. In IVF, embryo transfer is improved when hypothyroidism is treated.

The Endocrine Society recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.{{Cite web |date=26 March 2015 |title=Endocrine Experts Support Screening for Thyroid Dysfunction in Pregnant Women |url=https://www.endocrine.org/news-room/current-press-releases/endocrine-experts-support-screening-for-thyroid-dysfunction-in-pregnant-women |url-status=dead |archive-url=https://web.archive.org/web/20151008045642/https://www.endocrine.org/news-room/current-press-releases/endocrine-experts-support-screening-for-thyroid-dysfunction-in-pregnant-women |archive-date=8 October 2015 |access-date=4 October 2015 |website=Endocrine Society}} Universal screening for thyroid diseases during pregnancy is controversial, however, one study "supports the potential benefit of universal screening".{{cite journal | vauthors = Lepoutre T, Debiève F, Gruson D, Daumerie C | title = Reduction of miscarriages through universal screening and treatment of thyroid autoimmune diseases | journal = Gynecologic and Obstetric Investigation | volume = 74 | issue = 4 | pages = 265–273 | date = 2012-01-01 | pmid = 23147711 | doi = 10.1159/000343759 | s2cid = 1646888 | doi-access = }} Pregnant women may have antithyroid antibodies (5%–14% of pregnancies), poor thyroid function resulting in hypothyroidism, or both. Each is associated with risks:

The presence of Thyroid peroxidase antibodies at the outset of pregnancy are associated with a greater risk to the mother of hypothyroidism and thyroid impairment in the first year after delivery.{{cite journal | vauthors = Caturegli P, De Remigis A, Rose NR | title = Hashimoto thyroiditis: clinical and diagnostic criteria | journal = Autoimmunity Reviews | volume = 13 | issue = 4–5 | pages = 391–397 | date = 2014-04-01 | pmid = 24434360 | doi = 10.1016/j.autrev.2014.01.007 | series = Diagnostic criteria in Autoimmune diseases }}

The presence of antibodies is also associated with "a 2 to 4-fold increase in the risk of recurrent miscarriages, and 2 to 3-fold increased risk of preterm birth", however the reason why is unclear. Thyroid peroxidase antibodies are speculated to indicate other autoimmune processes against the placental-fetal unit.

Levothyroxine treatment in euthyroid women with thyroid autoimmunity does not significantly impact the relative risk of miscarriage and preterm delivery, or outcomes with live birth. "Therefore, no strong recommendations regarding the therapy in such scenarios could be made, but consideration on a case-by-case basis might be implemented."

Women who have low thyroid function that has not been stabilized are at greater risk of complications for both parent and child. Risks to the mother include gestational hypertension including preeclampsia and eclampsia, gestational diabetes, placental abruption, and postpartum hemorrhage. Risks to the infant include miscarriage, preterm delivery, low birth weight, neonatal respiratory distress, hydrocephalus, hypospadias, fetal death, infant intensive care unit admission, and neurodevelopmental delays (lower child IQ, language delay or global developmental delay).{{cite journal | vauthors = Gaberšček S, Zaletel K | title = Thyroid physiology and autoimmunity in pregnancy and after delivery | journal = Expert Review of Clinical Immunology | volume = 7 | issue = 5 | pages = 697–706; quiz 707 | date = September 2011 | pmid = 21895480 | doi = 10.1586/eci.11.42 | doi-access = free }}

Successful pregnancy outcomes are improved when hypothyroidism is treated. Levothyroxine treatment may be considered at lower TSH levels in pregnancy than in standard treatment. Liothyronine does not cross the fetal blood-brain barrier, so liothyronine (T₃) only or liothyronine + levothyroxine (T₃ + T₄) therapy is not indicated in pregnancy.

Close cooperation between the endocrinologist and obstetrician benefits the woman and the infant.{{cite journal | vauthors = Budenhofer BK, Ditsch N, Jeschke U, Gärtner R, Toth B | title = Thyroid (dys-)function in normal and disturbed pregnancy | journal = Archives of Gynecology and Obstetrics | volume = 287 | issue = 1 | pages = 1–7 | date = January 2013 | pmid = 23104052 | doi = 10.1007/s00404-012-2592-z | url = https://opus.bibliothek.uni-augsburg.de/opus4/frontdoor/index/index/docId/84394 | url-status = live | access-date = 16 January 2022 | s2cid = 24969196 | archive-url = https://web.archive.org/web/20220123170145/https://opus.bibliothek.uni-augsburg.de/opus4/frontdoor/index/index/docId/84394 | archive-date = 23 January 2022 }}{{cite journal | vauthors = Balucan FS, Morshed SA, Davies TF | title = Thyroid autoantibodies in pregnancy: their role, regulation and clinical relevance | journal = Journal of Thyroid Research | volume = 2013 | pages = 182472 | date = 2013 | pmid = 23691429 | pmc = 3652173 | doi = 10.1155/2013/182472 | doi-access = free }}

Hormonal changes and trophoblast expression of key immunomodulatory molecules lead to immunosuppression and fetal tolerance. The main players in regulation of the immune response are Tregs. Both cell-mediated and humoral immune responses are attenuated, resulting in immune tolerance and suppression of autoimmunity. It has been reported that during pregnancy, levels of thyroid peroxidase and thyroglobulin antibodies decrease.

Thyroid peroxidase antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. "[P]revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in premenopausal women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women [sic]."

Postpartum thyroiditis can occur in women with Hashimoto's. In healthy women, Postpartum thyroiditis can occur up to 1 year after delivery and should be differentiated from Hashimoto's thyroiditis as it is treated differently.{{cite journal | vauthors = Lee SY, Pearce EN | title = Assessment and treatment of thyroid disorders in pregnancy and the postpartum period | journal = Nature Reviews. Endocrinology | volume = 18 | issue = 3 | pages = 158–171 | date = March 2022 | pmid = 34983968 | pmc = 9020832 | doi = 10.1038/s41574-021-00604-z }}

After giving birth, Tregs rapidly decrease and immune responses are re-established. It may lead to the occurrence or aggravation of autoimmune thyroid disease.{{cite journal | vauthors = Weetman AP | title = Immunity, thyroid function and pregnancy: molecular mechanisms | journal = Nature Reviews. Endocrinology | volume = 6 | issue = 6 | pages = 311–318 | date = June 2010 | pmid = 20421883 | doi = 10.1038/nrendo.2010.46 | s2cid = 9900120 }} In up to 50% of females with thyroid peroxidase antibodies in the early pregnancy, thyroid autoimmunity in the postpartum period exacerbates in the form of postpartum thyroiditis.{{cite journal | vauthors = Lazarus JH | title = The continuing saga of postpartum thyroiditis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 96 | issue = 3 | pages = 614–616 | date = March 2011 | pmid = 21378224 | doi = 10.1210/jc.2011-0091 | doi-access = free }} Higher secretion of IFN-γ and IL-4, and lower plasma cortisol concentration during pregnancy has been reported in females with postpartum thyroiditis than in healthy females. It indicates that weaker immunosuppression during pregnancy could contribute to the postpartum thyroid dysfunction.{{cite journal | vauthors = Kokandi AA, Parkes AB, Premawardhana LD, John R, Lazarus JH | title = Association of postpartum thyroid dysfunction with antepartum hormonal and immunological changes | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 3 | pages = 1126–1132 | date = March 2003 | pmid = 12629095 | doi = 10.1210/jc.2002-021219 | doi-access = free }}

Several years after the delivery, the chimeric male cells can be detected in the maternal peripheral blood, thyroid, lung, skin, or lymph nodes. The fetal immune cells in the maternal thyroid gland may become activated and act as a trigger that may initiate or exaggerate the autoimmune thyroid disease. In Hashimoto's disease patients, fetal microchimeric cells were detected in thyroid in significantly higher numbers than in healthy females.{{cite journal | vauthors = Koopmans M, Kremer Hovinga IC, Baelde HJ, Harvey MS, de Heer E, Bruijn JA, Bajema IM | title = Chimerism occurs in thyroid, lung, skin and lymph nodes of women with sons | journal = Journal of Reproductive Immunology | volume = 78 | issue = 1 | pages = 68–75 | date = June 2008 | pmid = 18329105 | doi = 10.1016/j.jri.2008.01.002 }}

Hashimoto's disease is known to occur in chickens, rats, mice, dogs, and marmosets, but Graves' disease does not.{{cite journal | vauthors = McLachlan SM, Alpi K, Rapoport B | title = Review and hypothesis: does Graves' disease develop in non-human great apes? | journal = Thyroid | volume = 21 | issue = 12 | pages = 1359–1366 | date = December 2011 | pmid = 22066476 | pmc = 3229821 | doi = 10.1089/thy.2011.0209 }}

Pseudoscientific claims and "rogue practitioners" pose increasing risks to patients.{{Citation | vauthors = McDermott MT |title=Rogue Practitioners and Practices |date=2019 |work=Management of Patients with Pseudo-Endocrine Disorders: A Case-Based Pocket Guide |pages=23–30 | veditors = McDermott MT |url=https://link.springer.com/chapter/10.1007/978-3-030-22720-3_3 |access-date=2024-12-04 |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-030-22720-3_3 |isbn=978-3-030-22720-3}}

"We have seen practitioners who proclaim themselves to be experts in hormonal therapy without any formal training and who often promote hormonal treatments without adequate endocrine evaluations. We have seen practitioners who make astonishing promises regarding the benefits of herbal, supplemental, and other unproven therapies that they themselves sell in their offices and/or online. And we have seen what we know to be frankly harmful and even dangerous products that contain animal whole organ (most commonly thyroid and/or adrenal) extracts or hormonal injections that produce highly elevated levels of sex hormones (especially testosterone) without any concern for short-term patient safety or longterm outcomes. And we have heard anecdotal stories from patients who visited these practitioners and had no beneficial results or frankly concerning on-treatment results at a surprisingly high financial cost, even though they had been promised symptom improvement, safety, and full insurance coverage."

• Hashimoto's encephalopathy
• Myxedematous psychosis
• Hashitoxicosis
• Hoffmann Syndrome

{{Reflist}}

{{Medical condition classification and resources

| DiseasesDB = 5649

| ICD10 = {{ICD10|E|06|3|e|00}}

| ICD9 = {{ICD9|245.2}}

| ICDO =

| OMIM = 140300

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 949

| MeshID = D050031

| SNOMED CT = 66944004

|ICD11={{ICD11|5A03.20}}|ICD10CM={{ICD10CM|E06.3}}}}

{{Thyroid disease}}

{{Autoimmune diseases}}

{{Authority control}}

{{DEFAULTSORT:Hashimoto's Thyroiditis}}

Category:Aging-associated diseases

Category:Autoimmune diseases

Category:Endocrine diseases

Category:Wikipedia medicine articles ready to translate

Category:Wikipedia neurology articles ready to translate

Category:Thyroid disease

Category:Diseases named after discoverers