Hashimoto's thyroiditis

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Hashimoto's thyroiditis
Classification and external resources
ICD-10E06.3
ICD-9245.2
OMIM140300
DiseasesDB5649
MedlinePlus000371
eMedicinemed/949
Patient UKHashimoto's thyroiditis
MeSHD050031
 
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Hashimoto's thyroiditis
Classification and external resources
ICD-10E06.3
ICD-9245.2
OMIM140300
DiseasesDB5649
MedlinePlus000371
eMedicinemed/949
Patient UKHashimoto's thyroiditis
MeSHD050031

Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is attacked by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease.[1] It was first described by the Japanese specialist Hakaru Hashimoto in Germany in 1912.

Signs and symptoms[edit]

There are many symptoms that are attributed to Hashimoto's thyroiditis or Hashimoto's disease. The most common symptoms include the following: 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, and problems getting pregnant and maintaining pregnancy.

Hashimoto’s disease is about seven times more common in women than in men. It can occur in teens and young women, but more commonly shows up in middle age, particularly for men. People who get Hashimoto’s disease often have family members who have thyroid or other autoimmune diseases, and sometimes have other autoimmune diseases themselves.[2]

The thyroid gland may become firm, large, and lobulated in Hashimoto's thyroiditis, but changes in the thyroid can also be nonpalpable.[3] Enlargement of the thyroid is due to lymphocytic infiltration and fibrosis rather than tissue hypertrophy. Physiologically, antibodies against thyroid peroxidase (TPO) and/or thyroglobulin cause gradual destruction of follicles in the thyroid gland. Accordingly, the disease can be detected clinically by looking for these antibodies in the blood. It is also characterized by invasion of the thyroid tissue by leukocytes, mainly T-lymphocytes. A rare but serious complication is thyroid lymphoma, generally the B-cell type, non-Hodgkin lymphoma.[4]

Risk factors[edit]

A family history of thyroid disorders is common, with the HLA-DR5 gene most strongly implicated conferring a relative risk of 3 in the UK. In addition Hashimoto's thyroiditis may be associated with CTLA-4 (Cytotoxic T-lymphocyte Antigen-4) gene polymorphisms that result in reduced functioning of the gene's products, which are associated with negative regulation of T-lymphocyte activity.[5] Downregulatory gene polymorphisms affecting CTLA4 are also associated with autoimmune pathology seen in development of type I diabetes.[6] The strong genetic component underscoring this theory 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 aetiology.[7]

Preventable environmental factors, including high iodine intake, selenium deficiency, as well as infectious diseases and certain drugs, have been implicated in the development of autoimmune thyroid disease in genetically predisposed individuals.[8] The genes implicated vary in different ethnic groups and the incidence is increased in patients with chromosomal disorders, including Turner, Down's, and Klinefelter syndromes usually associated with autoantibodies against thyroglobulin and thyroperoxidase. Progressive depletion of these cells as the cytotoxic immune response develops leads to higher degrees of primary hypothyroidism, presenting with a poverty of T3/T4 levels, and compensatory elevations of TSH.

Recent research suggests a potential role for HHV-6 (possibly variant A) in the development or triggering of Hashimoto's thyroiditis.[9]

Pathophysiology[edit]

There are multiple suggested mechanisms by which the pathology of Hashimoto's thyroiditis develops.

Various autoantibodies may be present against thyroid peroxidase, thyroglobulin and TSH receptors, although a small percentage of patients may have none of these antibodies present. As indicated in various twin studies a percentage of the population may also have these antibodies without developing Hashimoto's thyroiditis. Nevertheless, antibody-dependent cell-mediated cytotoxicity is a substantial factor behind the apoptotic fall-out of Hashimoto's thyroiditis. Activation of cytotoxic T-lymphocytes (CD8+ T-cells) in response to cell-mediated immune response affected by helper T-lymphocytes (CD4+ T-cells) is central to thyrocyte destruction. As is characteristic of type IV hypersensitivities, recruitment of macrophages is another effect of the helper T-lymphocyte activation, with Th1 axis lymphocytes producing inflammatory cytokines within thyroid tissue to further macrophage activation and migration into the thyroid gland for direct effect.[citation needed]

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.[10]

Histologically, the hypersensitivity is seen as diffuse parenchymal infiltration by lymphocytes, particularly plasma B-cells, which can often be seen as secondary lymphoid follicles (germinal centers, not to be confused with the normally present colloid-filled follicles that constitute the thyroid). Atrophy of the colloid bodies is lined by Hürthle cells, cells with intensely eosinophilic, granular cytoplasm, a metaplasia from the normal cuboidal cells that constitute the lining of the thyroid follicles. Severe thyroid atrophy presents often with denser fibrotic bands of collagen that remains within the confines of the thyroid capsule.[11]

Diagnosis[edit]

Diagnosis is usually made by detecting elevated levels of anti-thyroid peroxidase antibodies in the serum, but seronegative (without circulating autoantibodies) thyroiditis is also possible.[12]

Given the relatively non-specific symptoms of initial hypothyroidism, Hashimoto's thyroiditis is often misdiagnosed as depression, cyclothymia, PMS, chronic fatigue syndrome, fibromyalgia and, less frequently, as ED or an anxiety disorder. On gross examination, there is often presentation of a hard goitre that is not painful to the touch;[10] other symptoms seen with hypothyroidism, such as periorbital myxedema, depends on the current state of progression of the response, especially given the usually gradual development of clinically relevant hypothyroidism. Testing for thyroid-stimulating hormone (TSH), free T3, free T4, and the anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO) and anti-microsomal antibodies can help obtain an accurate diagnosis.[13] Earlier assessment of the patient may present with elevated levels of thyroglobulin owing to the transient thyrotoxicosis as inflammation within the thyroid causes damage to the integrity of thyroid follicle storage of thyroglobulin; TSH is increased as the pituitary tries to compensate for decreased T4 .[citation needed]

Ultrasound imaging of the thyroid gland (right lobe longitudinal) in patient with Hashimoto Thyroiditis.

This exposure of the body to substantial amounts of previously isolated thyroid enzymes is thought to contribute to the exacerbation of tolerance breakdown, giving rise to the more pronounced symptoms seen later in the disease. Lymphocytic infiltration of the thyrocyte-associated tissues often leads to the histologically significant finding of germinal center development within the thyroid gland.

Hashimoto's when presenting as mania is known as Prasad's syndrome after Ashok Prasad, the psychiatrist who first described it.[14]

Treatment[edit]

Managing hormone levels[edit]

Hypothyroidism caused by Hashimoto's thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine, triiodothyronine or desiccated thyroid extract. A tablet taken once a day generally keeps the thyroid hormone levels normal. In most cases, the treatment needs to be taken for the rest of the patient's life. In the event that hypothyroidism is caused by Hashimoto's thyroiditis, it is recommended that the TSH levels be kept under 3.0.[15]

Selenium[edit]

Although the current clinical practice guidelines for hypothyroidism in adults do not indicate selenium supplementation,[16] a 1-year study of 46 patients found supplementing 80μg per day of selenium slowed several markers of disease progression.[17] Another study comparing 100μg and 200μg doses of selenium combined with levothyroxine in 88 female patients over 9 months found that 200μg was more effective.[18] A 2013 systemic review found there is still not enough evidence to definitively support or refute the efficacy of selenium for Hashimoto's thyroiditis, and urges more clinical trials are needed before efficacy can be proven.[19]

As a dietary supplement, the FDA recommends at least 55μg per day of selenium for adults with a tolerable upper intake level of 400μg.[20]

Low-level laser therapy[edit]

According to a study published in 2013, near-infrared low level laser therapy has been shown to be effective in phase two clinical trials at improving thyroid function.[21]

Gluten-free diet[edit]

Preliminary studies have suggested a correlation between Hashimoto's thyroiditis and celiac disease.[22] While it has not been rigorously explored, there are anecdotal reports that a gluten-free diet may reduce the autoimmune response responsible for thyroid degeneration.[23] A study published in January 2012 compared a group of confirmed celiac patients to a control group of healthy individuals, starting a gluten-free diet and continuing for one year.[24] While there was a higher occurrence of thyroiditis found amongst the celiac group, there was no reduction in their level of anti-TPO antibody, improvement in thyroid function, or change in thyroid volume reduction after one year without gluten. The study mentions that its results disagree with other studies, such as a prospective study published in August 2000 with 90 celiac patients, which found that thyroid-related serum antibodies tended to reduce during a gluten-free diet.[25]

Prognosis[edit]

Overt, symptomatic thyroid dysfunction is the most common complication, with about 5% of patients 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 Basedow-Graves disease with active orbitopathy (bulging, inflamed eyes). Rare cases of fibrous autoimmune thyroiditis present with severe dyspnea (shortness of breath) and dysphagia (difficulty swallowing), resembling aggressive thyroid tumors - but such symptoms always improve with surgery or corticosteroid therapy. Primary thyroid B cell lymphoma affects fewer than one in a thousand patients, and it is more likely to affect those with long-standing autoimmune thyroiditis.[26]

Epidemiology[edit]

This disorder is believed to be the most common cause of primary hypothyroidism in North America; as a cause of non-endemic goiter, it is among the most common.[27] An average of 1 to 1.5 in 1000 people have this disease.[27] It occurs between eight and fifteen times more often in women than in men. Though it may occur at any age, including in children, it is most often observed in women between 30 and 60 years of age.[26] It is more common in regions of high iodine dietary intake, and among people who are genetically susceptible.[26]

History[edit]

The explanation board of Hashimoto Dōri in Kyushu University

Also known as Hashimoto's disease, Hashimoto's thyroiditis is named after the Japanese physician Hakaru Hashimoto (1881−1934) of the medical school at Kyushu University,[28] who first described the symptoms of patients with struma lymphomatosa, an intense infiltration of lymphocytes within the thyroid, in 1912 in a German publication.[29] The report gave new insight into a condition (hypothyroidism) more commonly seen in areas of iodine deficiency that was occurring in the developed world, and without evident causation by dietary deficiency.

See also[edit]

References[edit]

  1. ^ Nakazawa, Donna (2008). The Autoimmune Epidemic. New York: Simon & Schuster. pp. 32–35. ISBN 978-0-7432-7775-4. 
  2. ^ "Hashimoto's disease fact sheet". Office on Women's Health, U.S. Department of Health and Human Services, womenshealth.gov (or girlshealth.gov). July 16, 2012. Retrieved 23 November 2014. 
  3. ^ Page 56 in: Staecker, Hinrich; Thomas R. Van De Water; Van de Water, Thomas R. (2006). Otolaryngology: basic science and clinical review. Stuttgart: Thieme. ISBN 0-86577-901-5. 
  4. ^ Dayan CM, Daniels GH (1996). "Chronic autoimmune thyroiditis". N Engl J Med. pp. 335:99–107. Retrieved 11 April 2014. 
  5. ^ Kavvoura, F. K.; Akamizu, T.; Awata, T.; Ban, Y.; Chistiakov, D. A.; Frydecka, I.; Ghaderi, A.; Gough, S. C.; Hiromatsu, Y. (2007). "Cytotoxic T-Lymphocyte Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Disease: A Meta-Analysis". Journal of Clinical Endocrinology & Metabolism 92 (8): 3162–70. doi:10.1210/jc.2007-0147. PMID 17504905. 
  6. ^ Jacobson, Eric M.; Tomer, Yaron (2007). "The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: Back to the future". Journal of Autoimmunity 28 (2–3): 85–98. doi:10.1016/j.jaut.2007.02.006. PMC 2043086. PMID 17369021. 
  7. ^ Chistiakov, Dimitry A (2005). "Immunogenetics of Hashimoto's thyroiditis". Journal of Autoimmune Diseases 2 (1): 1. doi:10.1186/1740-2557-2-1. PMC 555850. PMID 15762980. 
  8. ^ Saranac, L.; Zivanovic, S.; Bjelakovic, B.; Stamenkovic, H.; Novak, M.; Kamenov, B. (2011). "Why is the Thyroid So Prone to Autoimmune Disease". Hormone Research in Paediatrics 75 (3): 157–65. doi:10.1159/000324442. PMID 21346360. 
  9. ^ Caselli, Elisabetta; Zatelli, Maria Chiara; Rizzo, Roberta; Benedetti, Sabrina; Martorelli, Debora; Trasforini, Giorgio; Cassai, Enzo; Degli Uberti, Ettore C.; Di Luca, Dario (Oct 2012). Moore, Patrick S, ed. "Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto's thyroiditis". PLoS Pathogens 8 (10): e1002951. doi:10.1371/journal.ppat.1002951. PMC 3464215. PMID 23055929. 
  10. ^ a b Kumar, Vinay (2010). "24: The Endocrine System". Robbins and Cotran Pathologic Mechanisms of Disease (8th ed.). Philadelphia, PA: Elsevier. p. 1113. 
  11. ^ Kumar, Vinay (2010). "24: The Endocrine System". Robbins and Cotran Pathologic Mechanisms of Disease (8th ed.). Philadelphia, PA: Elsevier. pp. 1112–1113. 
  12. ^ Grani, Giorgio; Carbotta, Giovanni; Nesca, Angela; D’Alessandri, Mimma; Vitale, Martina; Del Sordo, Marianna; Fumarola, Angela (4 October 2014). "A comprehensive score to diagnose Hashimoto’s thyroiditis: a proposal". Endocrine. doi:10.1007/s12020-014-0441-5. 
  13. ^ Giannini, AJ (1986). The Biological Foundations of Clinical Psychiatry. New Hyde Park, NY: Medical Examination Publishing Company. pp. 193–198. ISBN 0-87488-449-7. 
  14. ^ "Prasad's syndrome" (PDF). 
  15. ^ "Does Your Doctor Know About the New TSH Lab Standards?". 
  16. ^ 2012 ATA/AACE Guidelines for Hypothyroidism in Adults
  17. ^ Nacamulli, D.; Mian, C.; Petricca, D.; Lazzarotto, F.; Barollo, S.; Pozza, D.; Masiero, S.; Faggian, D.; Plebani, M.; Girelli, M. E.; Mantero, F.; Betterle, C. (2009). "Influence of Physiological Dietary Selenium Supplementation on the Natural Course of Autoimmune Thyroiditis". Clinical Endocrinology 73 (4): 535–539. doi:10.1111/j.1365-2265.2009.03758.x. PMID 20039895. 
  18. ^ Turker, O.; Kumanlioglu, K.; Karapolat, I.; Dogan, I. (2006). "Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses". Journal of Endocrinology 190 (1): 151–156. doi:10.1677/joe.1.06661. PMID 16837619. 
  19. ^ Van Zuuren, E. J.; Albusta, A. Y.; Fedorowicz, Z.; Carter, B.; Pijl, H. (2013). "Selenium supplementation for Hashimoto's thyroiditis". In Van Zuuren, Esther J. "Cochrane Database of Systematic Reviews". The Cochrane database of systematic reviews 6: CD010223. doi:10.1002/14651858.CD010223.pub2. PMID 23744563. 
  20. ^ Dietary Supplement Fact Sheet: Selenium
  21. ^ Höfling, D. B.; Chavantes, M. C.; Juliano, A. G.; Cerri, G. G.; Knobel, M.; Yoshimura, E. M.; Chammas, M. C. (2012). "Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: A randomized, placebo-controlled clinical trial". Lasers in Medical Science 28 (3): 743–753. doi:10.1007/s10103-012-1129-9. PMID 22718472. 
  22. ^ "Connection Found Between Celiac Disease and Hashimoto's Thyroiditis". 
  23. ^ "Wendy vs. Autoimmune Hypothyroid". [unreliable medical source?]
  24. ^ Metso, Saara; Hyytiä-Ilmonen, Henni; Kaukinen, Katri; Huhtala, Heini; Jaatinen, Pia; Salmi, Jorma; Taurio, Jyrki; Collin, Pekka (2012). "Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study". Scandinavian Journal of Gastroenterology 47 (1): 43–8. doi:10.3109/00365521.2011.639084. PMID 22126672. 
  25. ^ Ventura A, Neri E, Ughi C, Leopaldi A, Citta A, Not T. Glutendependent diabetes-related and thyroid-related autoantibodies inpatients with celiac disease. J Pediatr 2000; 137: 263–65. http://www.ncbi.nlm.nih.gov/pubmed/10931424
  26. ^ a b c Fabrizio Monaco (2012). Thyroid Diseases. Taylor and Francis. p. 78. ISBN 9781439868393. 
  27. ^ a b Kumar, Vinay (2010). "24: The Endocrine System". Robbins and Cotran Pathologic Mechanisms of Disease (8th ed.). Philadelphia, PA: Elsevier. pp. 1111–205. 
  28. ^ Hakaru Hashimoto at Who Named It?
  29. ^ Hashimoto, H. (1912). "Zur Kenntnis der lymphomatösen Veränderung der Schilddrüse (Struma lymphomatosa)". Archiv für klinische Chirurgie (Berlin) 97: 219–248. 

External links[edit]