Hashimoto's thyroiditis (hypothyroidism)

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Hashimoto's thyroiditis & ME/CFS
Hashimoto's thyroiditis found in 17-20% of ME/CFS patients[1] Source: Sotzny et al (2018), EUROMENE project.
Hashimoto's thyroiditis or Hashimoto's disease (also known as chronic lymphocytic thyroiditis) is an autoimmune disease affecting thyroid function, where the body's immune system creates antibodies that attack and inflame the thyroid.

Hashimoto's thyroiditis is the most common cause of hypothyroidism (or underactive thyroid or low thyroid) in the United States. Hypothyroidism is an endocrine disorder in which the thyroid gland does not produce enough thyroid hormone called T4 (thyroxine), which is used to help the body use energy as well help maintain function of the brain, heart, muscle, and other organs.[2][3]

Hashimoto's thyroiditis is found in an estimated 17% - 20% of ME/CFS patients.[4][5]

Signs and symptoms[edit | edit source]

Human female body labeled with signs and symptoms of hypothyroidism

Symptoms of an underactive thyroid (hypothyroidism) due to Hashimoto's include:

Causes[edit | edit source]

There are many risk factors and potential causes for thyroid disease. Hashimoto's is the number one cause of hypothyroidism in the United States.[2]

Causes of hypothyroidism include:

  • Hashimoto's thyroiditis, which is an acquired form of thyroiditis
  • Congenital hypothyroidism, which is when a person is born with hypothyroidism
  • Thyroid surgery that removes all or part of the thyroid
  • Past radiation treatment of the thyroid
  • Other causes include certain medicines, too much or too little iodine in the diet, or pituitary disease (which is another endocrine disease).[6]

Hashimoto's thyroiditis[edit | edit source]

The exact cause of Hashimoto's thyroiditis is unknown. Many researchers and physicians believe genetics and/or a virus could play a role in the development of this autoimmune disease.[7]

Cellular hypothyroidism[edit | edit source]

Some patients may exhibit Hashimoto's hypothyroid symptoms, yet display normal ranges in their thyroid blood tests. This could be an indication of “cellular or peripheral hypothyroidism”, where there's a deficiency at the cellular level. While thyroid hormone production may be functioning properly, the transportation of thyroid hormone into cells will be hindered if there is mitochondrial dysfunction.[8]

Mitochondrial dysfunction has been implicated countless times, not only as a contributor to, but often cited as the immediate cause of ME/CFS symptoms.[9][10][11]

Viral triggers[edit | edit source]

Viruses are common triggers of Hashimoto's thyroiditis, and hypothyroidism. Epstein-Barr virus (EBV) and Human Herpesvirus 6 (HHV-6) are perhaps two of the most common viral triggers for Hashimoto. Others include Herpes Simplex 1 and 2 (HSV), Cytomegalovirus (CMV), Enterovirus, and Parvovirus B19.

ME/CFS[edit | edit source]

An estimated 17%-20% of ME/CFS patients are believed to also have Hashimoto's thyroiditis.[12][13]

A 2001 Swedish study of 219 chronic fatigue patients (90% women), used fine-needle aspiration (FNA) cytology to test thyroid function. 87 of 219 (40%) were diagnosed with cytological lymphocytic thyroiditis.[14]

Studies linking viruses to Hashimoto's and ME/CFS[edit | edit source]

Studies suggesting a viral trigger for Hashimoto's thyroiditis and autoimmune thyroiditis (AIT) that are also viruses commonly associated with ME/CFS.

Epstein-Barr virus serology in patients with autoimmune thyroiditis

J Vrbikova, I Janatkova, V Zamrazil, F Tomiska, T Fucikova[15]

 1996 Endocrinology study shows significantly higher presence of active Epstein-Barr virus (EBV) in those with autoimmune thyroiditis compared to healthy controls.

7 of 22 (32%) patients were positive for EBV early antigen (EA-D) antibodies, versus 2 of 35 (6%) controls.

Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

Elisabetta Caselli, Maria Chiara Zatelli, Roberta Rizzo, Sabrina Benedetti, Debora Martorelli, Giorgio Trasforini, Enzo Cassai, Ettore C. degli Uberti, Dario Di Luca, Riccardo Dolcetti[16]

 2012 Study using fine needle aspirates (FNA) thyroid biopsies found HHV-6 DNA in 28 of 34 (82%) Hashimoto's thyroiditis patients and 3 of 28 (10%) controls.
Inflammation and Increased Myxovirus Resistance Protein A Expression in Thyroid Tissue in the Early Stages of Hashimoto's Thyroiditis

Sara Salehi Hammerstad, Frode Lars Jahnsen, Sisko Tauriainen, Heikki Hyöty, Trond Paulsen, Ingrid Norheim, and Knut Dahl-Jørgensen[17]

 2013 Study found Enterovirus RNA in 11% of Hashimoto's thyroiditis (HT) patients, versus 0% of controls.
The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases

Andrea Janegova, Pavol Janega, Boris Rychly, Kristina Kuracinova, Pavel Babal[18]

 2015 Graves' and Hashimoto's disease specimens were used in this study, finding a high prevalence of EBV infection. "We assume that high prevalence of EBV infection in cases of Hashimoto's and Graves' diseases imply a potential aetiological role of EBV in autoimmune thyroiditis"
Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases

A Sultanova, M Cistjakovs, S Gravelsina, S Chapenko, S Roga, E Cunskis, Z Nora-Krukle, V Groma, I Ventina, M Murovska[19]

 2017 A study comparing the involvement of HHV-6 infection between autoimmune thyroiditis (AIT) patients and healthy controls. Thyroid gland biopsies confirmed active persistent HHV-6 infection in 18 of 44 (41%) AIT patients and 1 of 17 (6%) healthy controls.
Human herpesvirus 6A active infection in patients with autoimmune Hashimoto's thyroiditis

Noorossadat Seyyedi, Gholamreza Rafiei Dehbidi, Mozhgan Karimi, Amir Asgari, Babak Esmaeili, Farahnaz Zare, Ali Farhadi, Mohammad Hossein Dabbaghmanesh, Forough Saki, Abbas Behzad-Behbahani[20]

 2019 In this study, 38% of patients with Hashimoto’s disease had active HHV-6A infections.
Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto’s thyroiditis: A case-control study

Samir Naeim Assaad, Marwa Ahmed Meheissen, Eman Tayae Elsayed, Saher N. Alnakhal, Tarek M. Salema[21]

 2020 This study included 60 Hashimoto's thyroiditis patients and 60 healthy controls. Epstein-Barr virus (EBV) Early Antigen (EA) was positive in 20 of 60 (33%) HT patients and 4 of 60 (7%) healthy controls, indicating a higher prevalence of active EBV in Hashimoto patients.
HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis

Alina Sultanova, Maksims Cistjakovs, Liba Sokolovska, Katerina Todorova, Egils Cunskis, Modra Murovska[22]

 2020 Markers of active HHV-6 infection were predominantly found in patients with autoimmune thyroiditis (AIT). 56% of AIT patients (vs. 6% controls) were found to have active HHV-6 infection in thyroid gland tissue.

Sleep apnea[edit | edit source]

Hashimoto's thyroiditis (HT) and sleep apnea can both result in extreme fatigue. New evidence suggests a connection between Hashimoto's and obstructive sleep apnea (OSA). In fact, the association could be bi-directional, where either condition could potentially develop as a consequence of the other.[23]

HLA risk alleles[edit | edit source]

Variations in several human leukocyte antigen (HLA) complex family of genes have been studied as possible risk factors for Hashimoto thyroiditis. Associations have been found between Hashimoto's disease and the following HLA alleles:[24][25][26]

  • C*07:04
  • DQB1*03:03
  • DRB1
  • DRB1*04:10

ME/CFS and Hashimoto's genetics[edit | edit source]

In a large 2020 study, CFS patients with Human Leukocyte Antigen (HLA) risk alleles (C*07:04 and DQB1*03:03) were found to share the following autoimmune diseases, ordered by frequency:[26]

  1. Hashimoto's thyroiditis
  2. Psoriasis
  3. Rheumatoid arthritis
  4. Alopecia areata
  5. Crohn’s disease or ulcerative colitis

Diagnosis[edit | edit source]

Hashimoto's thyroiditis is usually diagnosed based on multiple examinations, often beginning with hypothyroid symptom evaluation. This can be accompanied by blood tests and ultrasound.

Blood tests indicating Hashimoto's disease include elevated levels of thyroperoxidase antibodies (TPO), and elevated levels of thyroid stimulating hormone (TSH). Other lab testing can include Thyroglobulin antibodies (Tg), Free thyroxine (T4), or Free triiodothyronine (T3).

This might be followed by an ultrasound to confirm an enlarged thyroid gland, and other features of Hashimoto's thyroiditis.[27]

Treatments[edit | edit source]

Hormone Replacement[edit | edit source]

Levothyroxine - If you are found to have a thyroid hormone deficiency, resulting in elevated TSH levels, your doctor might prescribe hormone replacement therapy. Levothyroxine is a synthetic thyroid hormone used to normalize TSH and hormone levels, leading to hypothyroid symptom improvement.[28]

Target Infection[edit | edit source]

Antivirals - If your Hashimoto's was triggered by a bacterial or viral infection, then suppressing the infection using antiviral treatment might improve symptoms.

Supplementation[edit | edit source]

Selenium - Selenium has been shown to decrease thyroperoxidase (TPO) antibody levels and improve overall symptoms associated with Hashimoto's Thyroiditis.[29][30] A 2017 study demonstrated that the combination of Selenium and Myo-inositol had an even greater effect.[31]

Supplements most commonly used to treat Epstein-Barr Virus (EBV) triggered Hashimoto's include:

Immunomodulator[edit | edit source]

Low-dose naltrexone (LDN) - LDN is an immunomodulating medication that many claim has improved their Hashimoto's symptoms. However, there is a lack of scientific studies to back up this claim.

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease". Autoimmunity Reviews. 17 (6): 601–609. June 1, 2018. doi:10.1016/j.autrev.2018.01.009. ISSN 1568-9972.
  2. ↑ 2.02.1 "Hashimoto's Thyroiditis". American Thyroid Association. Retrieved August 26, 2020.
  3. ↑ "Hypothyroidism (Underactive Thyroid) | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved August 26, 2020.
  4. ↑ "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease". Autoimmunity Reviews. 17 (6): 601–609. June 1, 2018. doi:10.1016/j.autrev.2018.01.009. ISSN 1568-9972.
  5. ↑ Castro-Marrero, Jesús; Faro, Mónica; Aliste, Luisa; Sáez-Francàs, Naia; Calvo, Natalia; Martínez-Martínez, Alba; de Sevilla, Tomás Fernández; Alegre, Jose (September 2017). "Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study". Psychosomatics. 58 (5): 533–543. doi:10.1016/j.psym.2017.04.010. ISSN 1545-7206. PMID 28596045.
  6. ↑ "Hypothyroidism (Underactive Thyroid) | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved October 21, 2020.
  7. ↑ "Hashimoto's Disease | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved October 21, 2020.
  8. ↑ Kelly, Tammas (December 2016). "A hypothesis on the mechanism of action of high-dose thyroid in refractory mood disorders". Medical Hypotheses. 97: 16–21. doi:10.1016/j.mehy.2016.09.022. ISSN 1532-2777. PMID 27876122.
  9. ↑ Myhill, Sarah; Booth, Norman E.; McLaren-Howard, John (January 15, 2009). "Chronic fatigue syndrome and mitochondrial dysfunction". International Journal of Clinical and Experimental Medicine. 2 (1): 1–16. ISSN 1940-5901. PMC 2680051. PMID 19436827.
  10. ↑ Tomas, Cara; Brown, Audrey E.; Newton, Julia L.; Elson, Joanna L. (March 1, 2019). "Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types". PeerJ. 7. doi:10.7717/peerj.6500. ISSN 2167-8359. PMC 6398432. PMID 30847260.
  11. ↑ Venter, Marianne; Tomas, Cara; Pienaar, Ilse S.; Strassheim, Victoria; Erasmus, Elardus; Ng, Wan-Fai; Howell, Neil; Newton, Julia L.; Van der Westhuizen, Francois H. (February 27, 2019). "MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants". Scientific Reports. 9 (1): 2914. doi:10.1038/s41598-019-39060-1. ISSN 2045-2322.
  12. ↑ "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease". Autoimmunity Reviews. 17 (6): 601–609. June 1, 2018. doi:10.1016/j.autrev.2018.01.009. ISSN 1568-9972.
  13. ↑ Castro-Marrero, Jesús; Faro, Mónica; Aliste, Luisa; Sáez-Francàs, Naia; Calvo, Natalia; Martínez-Martínez, Alba; de Sevilla, Tomás Fernández; Alegre, Jose (September 2017). "Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study". Psychosomatics. 58 (5): 533–543. doi:10.1016/j.psym.2017.04.010. ISSN 1545-7206. PMID 28596045.
  14. ↑ Wikland, B.; Löwhagen, T.; Sandberg, P. O. (March 24, 2001). "Fine-needle aspiration cytology of the thyroid in chronic fatigue". Lancet (London, England). 357 (9260): 956–957. doi:10.1016/s0140-6736(05)71654-8. ISSN 0140-6736. PMID 11289370.
  15. ↑ Vrbikova, J.; Janatkova, I.; Zamrazil, V.; Tomiska, F.; Fucikova, T. (1996). "Epstein-Barr virus serology in patients with autoimmune thyroiditis". Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association. 104 (1): 89–92. doi:10.1055/s-0029-1211428. ISSN 0947-7349. PMID 8750577.
  16. ↑ Caselli, Elisabetta; Zatelli, Maria Chiara; Rizzo, Roberta; Benedetti, Sabrina; Martorelli, Debora; Trasforini, Giorgio; Cassai, Enzo; degli Uberti, Ettore C.; Di Luca, Dario (October 4, 2012). "Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis". PLoS Pathogens. 8 (10). doi:10.1371/journal.ppat.1002951. ISSN 1553-7366. PMC 3464215. PMID 23055929.
  17. ↑ Hammerstad, Sara Salehi; Jahnsen, Frode Lars; Tauriainen, Sisko; Hyöty, Heikki; Paulsen, Trond; Norheim, Ingrid; Dahl-Jørgensen, Knut (March 2013). "Inflammation and Increased Myxovirus Resistance Protein A Expression in Thyroid Tissue in the Early Stages of Hashimoto's Thyroiditis". Thyroid. 23 (3): 334–341. doi:10.1089/thy.2012.0264. ISSN 1050-7256.
  18. ↑ Janegova, Andrea; Janega, Pavol; Rychly, Boris; Kuracinova, Kristina; Babal, Pavel (2015). "The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases". Endokrynologia Polska. 66 (2): 132–136. doi:10.5603/EP.2015.0020. ISSN 2299-8306. PMID 25931043.
  19. ↑ Sultanova, A.; Cistjakovs, M.; Gravelsina, S.; Chapenko, S.; Roga, S.; Cunskis, E.; Nora-Krukle, Z.; Groma, V.; Ventina, I.; Murovska, M. (January 2017). "Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 23 (1): 50.e1–50.e5. doi:10.1016/j.cmi.2016.09.023. ISSN 1469-0691. PMID 27693656.
  20. ↑ Seyyedi, Noorossadat; Dehbidi, Gholamreza Rafiei; Karimi, Mozhgan; Asgari, Amir; Esmaeili, Babak; Zare, Farahnaz; Farhadi, Ali; Dabbaghmanesh, Mohammad Hossein; Saki, Forough (November 2019). "Human herpesvirus 6A active infection in patients with autoimmune Hashimoto's thyroiditis". The Brazilian Journal of Infectious Diseases: An Official Publication of the Brazilian Society of Infectious Diseases. 23 (6): 435–440. doi:10.1016/j.bjid.2019.10.004. ISSN 1678-4391. PMID 31751524.
  21. ↑ Assaad, Samir Naeim; Meheissen, Marwa Ahmed; Elsayed, Eman Tayae; Alnakhal, Saher N.; Salem, Tarek M. (March 12, 2020). "Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto's thyroiditis: A case-control study". Journal of Clinical & Translational Endocrinology. 20. doi:10.1016/j.jcte.2020.100222. ISSN 2214-6237. PMC 7090364. PMID 32215255.
  22. ↑ Sultanova, Alina; Cistjakovs, Maksims; Sokolovska, Liba; Todorova, Katerina; Cunskis, Egils; Murovska, Modra (June 26, 2020). "HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis". Viruses. 12 (6). doi:10.3390/v12060689. ISSN 1999-4915. PMC 7354462. PMID 32604892.
  23. ↑ Xerfan, Ellen M.S.; Facina, Anamaria S.; Andersen, Monica L.; Tufik, Sergio; Tomimori, Jane (November 15, 2019). "Hashimoto Thyroiditis as a Cause or Consequence of Obstructive Sleep Apnea". Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine. 15 (11): 1703. doi:10.5664/jcsm.8054. ISSN 1550-9389. PMC 6853408. PMID 31739867.
  24. ↑ "SelfDecode | Blog". selfdecode.com. Retrieved August 26, 2020.
  25. ↑ Tashiro, Ryosuke; Niizuma, Kuniyasu; Khor, Seik-Soon; Tokunaga, Katsushi; Fujimura, Miki; Sakata, Hiroyuki; Endo, Hidenori; Inoko, Hidetoshi; Ogasawara, Koetsu (August 14, 2019). "Identification of HLA-DRB1*04:10 allele as risk allele for Japanese moyamoya disease and its association with autoimmune thyroid disease: A case-control study". PLOS ONE. 14 (8): e0220858. doi:10.1371/journal.pone.0220858. ISSN 1932-6203. PMC 6693760. PMID 31412073.
  26. ↑ 26.026.1 Lande, Asgeir; Fluge, Øystein; Strand, Elin B.; Flåm, Siri T.; Sosa, Daysi D.; Mella, Olav; Egeland, Torstein; Saugstad, Ola D.; Lie, Benedicte A. (March 24, 2020). "Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Scientific Reports. 10 (1): 5267. doi:10.1038/s41598-020-62157-x. ISSN 2045-2322.
  27. ↑ "Hashimoto's Thyroiditis". American Thyroid Association. Retrieved August 26, 2020.
  28. ↑ "Hashimoto's disease - Diagnosis and treatment - Mayo Clinic". Mayo Clinic. Retrieved October 18, 2020.
  29. ↑ Ventura, Mara; Melo, Miguel; Carrilho, Francisco (2017). "Selenium and Thyroid Disease: From Pathophysiology to Treatment". International Journal of Endocrinology. doi:10.1155/2017/1297658. ISSN 1687-8337. PMC 5307254. PMID 28255299.
  30. ↑ van Zuuren, Esther J.; Albusta, Amira Y.; Fedorowicz, Zbys; Carter, Ben; Pijl, Hanno (March 2014). "Selenium Supplementation for Hashimoto's Thyroiditis: Summary of a Cochrane Systematic Review". European Thyroid Journal. 3 (1): 25–31. doi:10.1159/000356040. ISSN 2235-0640. PMC 4005265. PMID 24847462.
  31. ↑ Nordio, M.; Basciani, S. (June 2017). "Myo-inositol plus selenium supplementation restores euthyroid state in Hashimoto's patients with subclinical hypothyroidism". European Review for Medical and Pharmacological Sciences. 21 (2 Suppl): 51–59. ISSN 2284-0729. PMID 28724185.

antibodies Antibodies or immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

human leukocyte antigen complex (HLA) - A set of genes responsible for a given person's immune response to potential threats. Specifically, HLA genes encode proteins which help the immune system to distinguish the body's own proteins from proteins which are made by foreign invaders like bacteria and viruses. The HLA complex can vary greatly from person to person, generating unique immune and allergic responses. (Learn more: mecfsresearchreview.me)

antibodies Antibodies or immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

Category:immunomodulators|immunomodulator]]

immunomodulator a substance that affects the functioning of the immune system

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