COVID-19-associated thyroid diseases: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
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==Overview== | ==Overview== | ||
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==Pathophysiology== | ==Pathophysiology== | ||
The exact pathogenesis of COVID-19-associated thyroid diseases is not fully understood. However, the following hypotheses have been suggested for the development of thyroid dysfunction in COVID-19 patients. | The exact pathogenesis of COVID-19-associated thyroid diseases is not fully understood. However, the following hypotheses have been suggested for the development of thyroid dysfunction in COVID-19 patients. <ref name="pmid33765288">{{cite journal| author=Lisco G, De Tullio A, Jirillo E, Giagulli VA, De Pergola G, Guastamacchia E | display-authors=etal| title=Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects. | journal=J Endocrinol Invest | year= 2021 | volume= 44 | issue= 9 | pages= 1801-1814 | pmid=33765288 | doi=10.1007/s40618-021-01554-z | pmc=7992516 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33765288 }} </ref> <ref name="pmid32652001">{{cite journal| author=Lazartigues E, Qadir MMF, Mauvais-Jarvis F| title=Endocrine Significance of SARS-CoV-2's Reliance on ACE2. | journal=Endocrinology | year= 2020 | volume= 161 | issue= 9 | pages= | pmid=32652001 | doi=10.1210/endocr/bqaa108 | pmc=7454499 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32652001 }} </ref> <ref name="pmid33241508">{{cite journal| author=Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P| title=Impact of COVID-19 on the thyroid gland: an update. | journal=Rev Endocr Metab Disord | year= 2021 | volume= 22 | issue= 4 | pages= 803-815 | pmid=33241508 | doi=10.1007/s11154-020-09615-z | pmc=7688298 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33241508 }} </ref> <ref name="pmid26071885">{{cite journal| author=Fliers E, Bianco AC, Langouche L, Boelen A| title=Thyroid function in critically ill patients. | journal=Lancet Diabetes Endocrinol | year= 2015 | volume= 3 | issue= 10 | pages= 816-25 | pmid=26071885 | doi=10.1016/S2213-8587(15)00225-9 | pmc=4979220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26071885 }} </ref> <ref name="pmiddoi:10.1210/clinem/dgaa813">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=doi:10.1210/clinem/dgaa813 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref> <ref name="pmid16060914">{{cite journal| author=Leow MK, Kwek DS, Ng AW, Ong KC, Kaw GJ, Lee LS| title=Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). | journal=Clin Endocrinol (Oxf) | year= 2005 | volume= 63 | issue= 2 | pages= 197-202 | pmid=16060914 | doi=10.1111/j.1365-2265.2005.02325.x | pmc=7188349 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16060914 }} </ref> | ||
*Angiotensin-converting enzyme 2 (ACE2) receptors are essentially involved in SARS-CoV-2 internalization into host cells. | *[[Angiotensin-converting enzyme 2]] ([[ACE2]]) receptors are essentially involved in [[SARS-CoV-2]] internalization into host cells. The [[thyroid gland]] is amongst the organs which have the highest levels of [[ACE2]] expression and activity. Therefore, following [[SARS-CoV-2]] infection, thyroid damage could result from either a direct or immune-mediated injury. | ||
*[[COVID-19]] may also cause an immune system imbalance and, in severe cases, a [[cytokine storm]], which may break [[immunotolerance]] in susceptible patients, leading to new onset of immune-mediated [[thyroiditis]], exacerbating a previous [[thyroid disease]], or inducing a recurrence of [[thyroid disease]]. | |||
*COVID-19 may also cause an immune system imbalance and in severe cases a cytokine storm, which may break immunotolerance in susceptible patients, leading to new onset of immune-mediated thyroiditis, exacerbating a previous thyroid disease, or inducing a recurrence of thyroid disease. | *The other potential pathophysiology for the development of [[thyroid disease]] in [[COVID-19]] could be an underlying [[euthyroid sick syndrome]], also known as [[nonthyroidal illness syndrome]] ([[NTIS]]), caused by critical illness. Patients with the [[euthyroid sick syndrome]] are often characterized by low [[T3]] concentration, along with a normal or low serum [[TSH]]. [[T4]] concentration may be low in more severe or prolonged illnesses. | ||
* The fourth hypothesis is that [[hypothalamic]]-[[pituitary]]-[[thyroid]] ([[HPT]]) axis dysfunction in [[COVID-19]] Patients results in a decresaed level of serum [[TSH]] in patients with [[SARS-CoV-2]], causing secondary causes of [[hypothyroidism]] (central hypothyroidism). | |||
==Causes== | ==Causes== | ||
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==Differentiating COVID-19-associated thyroid diseases from other Diseases== | ==Differentiating COVID-19-associated thyroid diseases from other Diseases== | ||
* Differential diagnosis of [[hyperthyroidism]] in | * Differential diagnosis of [[hyperthyroidism]] in [[COVID-19]] patients may include: <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> <ref name="pmid32843467">{{cite journal| author=Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ| title=Subacute thyroiditis associated with COVID-19. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 8 | pages= | pmid=32843467 | doi=10.1136/bcr-2020-237336 | pmc=7449350 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32843467 }} </ref> <ref name="pmid32504458">{{cite journal| author=Asfuroglu Kalkan E, Ates I| title=A case of subacute thyroiditis associated with Covid-19 infection. | journal=J Endocrinol Invest | year= 2020 | volume= 43 | issue= 8 | pages= 1173-1174 | pmid=32504458 | doi=10.1007/s40618-020-01316-3 | pmc=7273820 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32504458 }} </ref> <ref name="pmid32780854">{{cite journal| author=Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F | display-authors=etal| title=Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 10 | pages= | pmid=32780854 | doi=10.1210/clinem/dgaa537 | pmc=7454668 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32780854 }} </ref> <ref name="pmid33370933">{{cite journal| author=Chakraborty U, Ghosh S, Chandra A, Ray AK| title=Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 12 | pages= | pmid=33370933 | doi=10.1136/bcr-2020-239953 | pmc=7750881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33370933 }} </ref> <ref name="pmid33005461">{{cite journal| author=Campos-Barrera E, Alvarez-Cisneros T, Davalos-Fuentes M| title=Subacute Thyroiditis Associated with COVID-19. | journal=Case Rep Endocrinol | year= 2020 | volume= 2020 | issue= | pages= 8891539 | pmid=33005461 | doi=10.1155/2020/8891539 | pmc=7522602 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33005461 }} </ref> <ref name="pmid32668831">{{cite journal| author=Tee LY, Harjanto S, Rosario BH| title=COVID-19 complicated by Hashimoto's thyroiditis. | journal=Singapore Med J | year= 2021 | volume= 62 | issue= 5 | pages= 265 | pmid=32668831 | doi=10.11622/smedj.2020106 | pmc=8801861 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32668831 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32738929">{{cite journal| author=Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A | display-authors=etal| title=SARS-CoV-2-related atypical thyroiditis. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 9 | pages= 739-741 | pmid=32738929 | doi=10.1016/S2213-8587(20)30266-7 | pmc=7392564 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32738929 }} </ref> <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> | ||
**[[Graves' disease]] | **[[Graves' disease]] | ||
**[[Subacute thyroiditis]] | **[[Subacute thyroiditis]] | ||
**[[ | ** [[Painless thyroiditis]] | ||
* Differential diagnosis of [[hypothyroidism]] in in [[COVID-19]] patients may include: | |||
** Primary hypothyroidism: | |||
***[[Autoimmune thyroiditis]]([[Hashimoto's thyroiditis]]) | |||
***[[Subacute granulomatous (de Quervain’s) thyroiditis]] | |||
** [[Secondary hypothyroidism]] | |||
*** [[Central Hypothyroidism]]] | |||
*For a complete list of differential diagnoses of hyperthyroidism, please click [[Hyperthyroidism#Differentiating the causes of thyrotoxicosis|here]]. | *For a complete list of differential diagnoses of hyperthyroidism, please click [[Hyperthyroidism#Differentiating the causes of thyrotoxicosis|here]]. | ||
*For a complete list of differential diagnoses of hypothyroidism, please click [[Hypothyroidism#Differentiating different causes of hypothyroidism|here]]. | *For a complete list of differential diagnoses of hypothyroidism, please click [[Hypothyroidism#Differentiating different causes of hypothyroidism|here]]. | ||
*For a complete list of differential diagnoses of euthyroid sick syndrome, please click [[Euthyroid sick syndrom#Differentiating Euthyroid sick syndrome from other Diseases|here]]. | *For a complete list of differential diagnoses of the euthyroid sick syndrome, please click [[Euthyroid sick syndrom#Differentiating Euthyroid sick syndrome from other Diseases|here]]. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Several cases of [[subacute thyroiditis]], [[Hashimoto thyroiditis]], [[myxedema coma]], [[Grave's disease]], [[atypical thyroiditis]], [[thyrotoxicosis]] have been reported in COVID-19 patients worldwide <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> <ref name="pmid32843467">{{cite journal| author=Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ| title=Subacute thyroiditis associated with COVID-19. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 8 | pages= | pmid=32843467 | doi=10.1136/bcr-2020-237336 | pmc=7449350 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32843467 }} </ref> <ref name="pmid32504458">{{cite journal| author=Asfuroglu Kalkan E, Ates I| title=A case of subacute thyroiditis associated with Covid-19 infection. | journal=J Endocrinol Invest | year= 2020 | volume= 43 | issue= 8 | pages= 1173-1174 | pmid=32504458 | doi=10.1007/s40618-020-01316-3 | pmc=7273820 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32504458 }} </ref> <ref name="pmid32780854">{{cite journal| author=Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F | display-authors=etal| title=Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 10 | pages= | pmid=32780854 | doi=10.1210/clinem/dgaa537 | pmc=7454668 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32780854 }} </ref> <ref name="pmid33370933">{{cite journal| author=Chakraborty U, Ghosh S, Chandra A, Ray AK| title=Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 12 | pages= | pmid=33370933 | doi=10.1136/bcr-2020-239953 | pmc=7750881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33370933 }} </ref> <ref name="pmid33005461">{{cite journal| author=Campos-Barrera E, Alvarez-Cisneros T, Davalos-Fuentes M| title=Subacute Thyroiditis Associated with COVID-19. | journal=Case Rep Endocrinol | year= 2020 | volume= 2020 | issue= | pages= 8891539 | pmid=33005461 | doi=10.1155/2020/8891539 | pmc=7522602 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33005461 }} </ref> <ref name="pmid32668831">{{cite journal| author=Tee LY, Harjanto S, Rosario BH| title=COVID-19 complicated by Hashimoto's thyroiditis. | journal=Singapore Med J | year= 2021 | volume= 62 | issue= 5 | pages= 265 | pmid=32668831 | doi=10.11622/smedj.2020106 | pmc=8801861 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32668831 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32738929">{{cite journal| author=Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A | display-authors=etal| title=SARS-CoV-2-related atypical thyroiditis. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 9 | pages= 739-741 | pmid=32738929 | doi=10.1016/S2213-8587(20)30266-7 | pmc=7392564 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32738929 }} </ref> <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> | * Data on the exact epidemiology and demographics of [[thyroid diseases]] in [[COVID-19]] patients are lacking. | ||
* Several cases of [[subacute thyroiditis]], [[Hashimoto thyroiditis]], [[myxedema coma]], [[Grave's disease]], [[atypical thyroiditis]], [[thyrotoxicosis]], [[sick euthyroid syndrome]] have been reported in [[COVID-19]] patients worldwide. <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> <ref name="pmid32843467">{{cite journal| author=Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ| title=Subacute thyroiditis associated with COVID-19. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 8 | pages= | pmid=32843467 | doi=10.1136/bcr-2020-237336 | pmc=7449350 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32843467 }} </ref> <ref name="pmid32504458">{{cite journal| author=Asfuroglu Kalkan E, Ates I| title=A case of subacute thyroiditis associated with Covid-19 infection. | journal=J Endocrinol Invest | year= 2020 | volume= 43 | issue= 8 | pages= 1173-1174 | pmid=32504458 | doi=10.1007/s40618-020-01316-3 | pmc=7273820 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32504458 }} </ref> <ref name="pmid32780854">{{cite journal| author=Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F | display-authors=etal| title=Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 10 | pages= | pmid=32780854 | doi=10.1210/clinem/dgaa537 | pmc=7454668 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32780854 }} </ref> <ref name="pmid33370933">{{cite journal| author=Chakraborty U, Ghosh S, Chandra A, Ray AK| title=Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 12 | pages= | pmid=33370933 | doi=10.1136/bcr-2020-239953 | pmc=7750881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33370933 }} </ref> <ref name="pmid33005461">{{cite journal| author=Campos-Barrera E, Alvarez-Cisneros T, Davalos-Fuentes M| title=Subacute Thyroiditis Associated with COVID-19. | journal=Case Rep Endocrinol | year= 2020 | volume= 2020 | issue= | pages= 8891539 | pmid=33005461 | doi=10.1155/2020/8891539 | pmc=7522602 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33005461 }} </ref> <ref name="pmid32668831">{{cite journal| author=Tee LY, Harjanto S, Rosario BH| title=COVID-19 complicated by Hashimoto's thyroiditis. | journal=Singapore Med J | year= 2021 | volume= 62 | issue= 5 | pages= 265 | pmid=32668831 | doi=10.11622/smedj.2020106 | pmc=8801861 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32668831 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32738929">{{cite journal| author=Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A | display-authors=etal| title=SARS-CoV-2-related atypical thyroiditis. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 9 | pages= 739-741 | pmid=32738929 | doi=10.1016/S2213-8587(20)30266-7 | pmc=7392564 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32738929 }} </ref> <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> | |||
==Risk Factors== | ==Risk Factors== | ||
Line 51: | Line 52: | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
A number of observational studies have shown that [[COVID-19]] infection may be linked to some [[thyroid diseases]], including: | A number of observational studies have shown that [[COVID-19]] infection may be linked to some [[thyroid diseases]], including: <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> <ref name="pmid32843467">{{cite journal| author=Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ| title=Subacute thyroiditis associated with COVID-19. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 8 | pages= | pmid=32843467 | doi=10.1136/bcr-2020-237336 | pmc=7449350 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32843467 }} </ref> <ref name="pmid32504458">{{cite journal| author=Asfuroglu Kalkan E, Ates I| title=A case of subacute thyroiditis associated with Covid-19 infection. | journal=J Endocrinol Invest | year= 2020 | volume= 43 | issue= 8 | pages= 1173-1174 | pmid=32504458 | doi=10.1007/s40618-020-01316-3 | pmc=7273820 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32504458 }} </ref> <ref name="pmid32780854">{{cite journal| author=Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F | display-authors=etal| title=Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 10 | pages= | pmid=32780854 | doi=10.1210/clinem/dgaa537 | pmc=7454668 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32780854 }} </ref> <ref name="pmid33370933">{{cite journal| author=Chakraborty U, Ghosh S, Chandra A, Ray AK| title=Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity. | journal=BMJ Case Rep | year= 2020 | volume= 13 | issue= 12 | pages= | pmid=33370933 | doi=10.1136/bcr-2020-239953 | pmc=7750881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33370933 }} </ref> <ref name="pmid33005461">{{cite journal| author=Campos-Barrera E, Alvarez-Cisneros T, Davalos-Fuentes M| title=Subacute Thyroiditis Associated with COVID-19. | journal=Case Rep Endocrinol | year= 2020 | volume= 2020 | issue= | pages= 8891539 | pmid=33005461 | doi=10.1155/2020/8891539 | pmc=7522602 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33005461 }} </ref> <ref name="pmid32668831">{{cite journal| author=Tee LY, Harjanto S, Rosario BH| title=COVID-19 complicated by Hashimoto's thyroiditis. | journal=Singapore Med J | year= 2021 | volume= 62 | issue= 5 | pages= 265 | pmid=32668831 | doi=10.11622/smedj.2020106 | pmc=8801861 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32668831 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32984743">{{cite journal| author=Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T | display-authors=etal| title=Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. | journal=J Endocr Soc | year= 2020 | volume= 4 | issue= 10 | pages= bvaa130 | pmid=32984743 | doi=10.1210/jendso/bvaa130 | pmc=7499619 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32984743 }} </ref> <ref name="pmid32738929">{{cite journal| author=Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A | display-authors=etal| title=SARS-CoV-2-related atypical thyroiditis. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 9 | pages= 739-741 | pmid=32738929 | doi=10.1016/S2213-8587(20)30266-7 | pmc=7392564 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32738929 }} </ref> <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> | ||
*[[Subacute thyroiditis]] | *[[Subacute thyroiditis]] | ||
*[[Graves’ disease]] | *[[Graves’ disease]] | ||
Line 57: | Line 59: | ||
*[[Thyrotoxicosis]] | *[[Thyrotoxicosis]] | ||
*[[Hashimoto’s thyroiditis]] | *[[Hashimoto’s thyroiditis]] | ||
*[[Prognosis]] has generally been good in most cases of [[COVID-19]] patients with [[hyperthyroidism]]/[[hypothyroidism]]. | |||
**In a patient with subacute thyroiditis, the thyroid function and inflammatory markers normalized in 40 days. <ref name="pmid32436948">{{cite journal| author=Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F| title=Subacute Thyroiditis After Sars-COV-2 Infection. | journal=J Clin Endocrinol Metab | year= 2020 | volume= 105 | issue= 7 | pages= | pmid=32436948 | doi=10.1210/clinem/dgaa276 | pmc=7314004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32436948 }} </ref> | |||
*In a study on 154 COVID-19 patients, Low fT3 (i.e., euthyroid sick syndrome) was associated with higher mortality and increased [[IL-6]], suggesting poor [[prognosis]] in these patients. <ref name="pmid34760673">{{cite journal| author=Dabas A, Singh H, Goswami B, Kumar K, Dubey A, Jhamb U | display-authors=etal| title=Thyroid Dysfunction in COVID-19. | journal=Indian J Endocrinol Metab | year= 2021 | volume= 25 | issue= 3 | pages= 198-201 | pmid=34760673 | doi=10.4103/ijem.ijem_195_21 | pmc=8547402 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34760673 }} </ref> | |||
==Diagnosis== | ==Diagnosis== | ||
Line 64: | Line 70: | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
The symptoms | The symptoms of clinical [[hyperthyroidism]] in [[COVID-19]] patients are similar to [[hyperthyroidism]] in the general population. | ||
The most common symptoms include: | |||
* [[Palpitations]] | |||
* [[Insomnia]] | |||
* [[Anxiety]] | |||
* [[Weight loss]] | |||
* [[Heat intolerance]] | |||
* [[Diarrhea]] | |||
The symptoms of clinical [[hypothyroidism]] in [[COVID-19]] patients are similar to [[hypothyroidism]] in the general population. | |||
The most common symptoms include: | The most common symptoms include: | ||
* [[Fatigue]] | * [[Fatigue]] | ||
Line 73: | Line 88: | ||
* [[Weight gain]] | * [[Weight gain]] | ||
* [[Hoarseness]] | * [[Hoarseness]] | ||
* [[Depression]] | * [[Depression]] | ||
* [[Emotional lability]] | * [[Emotional lability]] | ||
Line 81: | Line 95: | ||
* [[Constipation]] | * [[Constipation]] | ||
* Slowed speech and movements | * Slowed speech and movements | ||
* [[Hyperlipidemia]] | * [[Hyperlipidemia]] | ||
* [[Galactorrhea]] | * [[Galactorrhea]] | ||
If accompanied by [[thyroiditis]] | * [[Myxedema coma]] (with [[Edema|non-pitting edema]]) | ||
If accompanied by [[thyroiditis]]: | |||
* [[Sore throat]] | * [[Sore throat]] | ||
* [[Periorbital edema]] | * [[Periorbital edema]] | ||
The | ===Physical Examination=== | ||
The most common physical examination findings in patients with '''[[hyperthyroidism]]''' include: <ref>{{Cite journal | |||
* [[ | | author = [[Terry J. Smith]] & [[Laszlo Hegedus]] | ||
* [[ | | title = Graves' Disease | ||
* [[ | | journal = [[The New England journal of medicine]] | ||
* [[ | | volume = 375 | ||
* [[ | | issue = 16 | ||
* [[ | | pages = 1552–1565 | ||
* | | year = 2016 | ||
| month = October | |||
| doi = 10.1056/NEJMra1510030 | |||
| pmid = 27797318 | |||
}}</ref> | |||
* [[Tachycardia]] | |||
* [[Stare]] | |||
* [[Eyelid lag]] | |||
* [[Resting tremor]] | |||
* [[Hyperreflexia]] | |||
* Warm, moist, and smooth skin | |||
* In patients with Graves's disease: | |||
** Localized dermopathy (i.e., [[pretibial myxedema]]) | |||
** [[Proptosis]] ([[exophthalmos]]) | |||
** [[Goiter]] | |||
The most common physical examination findings in patients with '''[[hypothyroidism]]''' include: | |||
* [[Myxedema]]: in patients with Hashimoto's thyroiditis | |||
* [[Bradycardia]] | |||
* [[Dry skin]] | |||
* Coarse hair | |||
* Enlarged [[thyroid gland]] or presence of [[goiter]] | |||
* Small or shrunken [[thyroid gland]] (late in the disease) | |||
*[[Bradypnea]] | |||
* Slowed [[speech]] | |||
* [[Reflexes|Slowed reflexes]] | |||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
The laboratory findings in '''[[hyperthyroidism]]''' are: | |||
*Elevated levels of serum [[thyroxine]] ([[T4]]) and [[triiodothyronine]] ([[T3]]). | |||
*Undetectable serum TSH. | |||
*Total [[T4]] and [[T3]] measurements are influenced by multiple conditions affecting serum [[thyroxine-binding globulin]] ([[TBG]]). Thus, the measurement of free thyroid hormones; [[free T4]] ([[FT4]]) and [[free T3]] ([[fT3]]), is the gold standard for the diagnosis of [[Graves' disease]].<ref name="pmid17673120">{{cite journal |vauthors=Dufour DR |title=Laboratory tests of thyroid function: uses and limitations |journal=Endocrinol. Metab. Clin. North Am. |volume=36 |issue=3 |pages=579–94, v |year=2007 |pmid=17673120 |doi=10.1016/j.ecl.2007.04.003 |url=}}</ref> | |||
* Antibodies against the [[TSH]] receptor ([[TRAbs]]) are pathognomonic for [[Graves' disease]]. They are detectable in the serum of about 98% of untreated patients.<ref name="pmid20594972">{{cite journal |vauthors=Zöphel K, Roggenbuck D, Schott M |title=Clinical review about TRAb assay's history |journal=Autoimmun Rev |volume=9 |issue=10 |pages=695–700 |year=2010 |pmid=20594972 |doi=10.1016/j.autrev.2010.05.021 |url=}}</ref> Detection of TRAbs rules out other causes of thyrotoxicosis.<ref name="pmid23539719">{{cite journal |vauthors=Barbesino G, Tomer Y |title=Clinical review: Clinical utility of TSH receptor antibodies |journal=J. Clin. Endocrinol. Metab. |volume=98 |issue=6 |pages=2247–55 |year=2013 |pmid=23539719 |pmc=3667257 |doi=10.1210/jc.2012-4309 |url=}}</ref> | |||
* Anti-thyroid peroxidase (TPO) and antithyroglobulin (Tg) antibodies are also detectable in many patients with Graves' disease, but it is not recommended to measure these antibodies for diagnosis in all patients. | |||
The laboratory findings in '''[[hypothyroidism]]''' are: | |||
*Increased [[Thyroid-stimulating hormone]] (TSH) | |||
*Decreased Free [[T3]] and Free [[T4]] | |||
*[[TSH]] may be decreased in the transient hyperthyroid state <ref>{{cite journal|last=Simmons|first=PJ|title=Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a role of interleukin-1beta and interleukin-6|journal=Endocrinology|year=1998|volume=139|issue=7|pages=3158–3186|pmid=9645688|doi=10.1210/en.139.7.3148}}</ref> | |||
* Thyroid antibodies are usually positive in patients with [[Hashimoto's thyroiditis]]: | |||
** [[thyroid peroxidase|Anti-thyroid peroxidase]] antibodies (anti-[[TPO]]) (correlates with the disease severity) | |||
** [[thyroglobulin|Anti-thyroglobulin]] antibodies (anti-Tg) | |||
** [[Antimicrosomal antibody|Anti-microsomal antibodies]] can help obtain an accurate diagnosis <ref>{{cite book |last1= Giannini |first1= AJ |authorlink1= |title= The Biological Foundations of Clinical Psychiatry |url= |year= 1986 |publisher= Medical Examination Publishing Company |location= New Hyde Park, NY |language= |isbn= 0-87488-449-7 |oclc= |doi= |id= |page= |pages= 193–198 |quote= |ref= |bibcode= }}</ref> | |||
The laboratory findings in '''[[euthyroid sick syndrome]]''' are: | |||
{| class="wikitable" | |||
! style="background: #4479BA; color: #FFFFFF; " | Euthyroid sick syndrome | |||
! style="background: #4479BA; color: #FFFFFF; " | T3 | |||
(80-180 ng/dl) | |||
! style="background: #4479BA; color: #FFFFFF; " | T4 | |||
(4.6-12 ug/dl) | |||
! style="background: #4479BA; color: #FFFFFF; " | FT4 | |||
(0.7-1.9 ng/dl) | |||
! style="background: #4479BA; color: #FFFFFF; " | TSH | |||
(0.4 to 4.0mIU/L) | |||
! style="background: #4479BA; color: #FFFFFF; " | Reverse T3 | |||
'''(90 to 350'''pg/mL) | |||
|- | |||
|Mild [[euthyroid sick syndrome]] | |||
|↓ | |||
|N | |||
|N | |||
|N | |||
|'''↑''' | |||
|- | |||
|Moderate [[euthyroid sick syndrome]] | |||
|↓ | |||
|N | |||
|N/↓ | |||
|N/↓ | |||
|'''↑''' | |||
|- | |||
|Severe [[euthyroid sick syndrome]] | |||
|↓ | |||
|↓ | |||
|N/↓ | |||
|↓ | |||
|'''↑''' | |||
|- | |||
|Recovery | |||
|N/↓ | |||
|N | |||
|N | |||
|N | |||
|N/'''↑''' | |||
|} | |||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
* There are no [[The electrocardiogram|ECG]] findings associated with [[COVID-19|COVID-1]]9-associated [[thyroid disease]]. | * There are no [[The electrocardiogram|ECG]] findings associated with [[COVID-19|COVID-1]]9-associated [[thyroid disease]]. | ||
* However, the following findings may be seen on [[The electrocardiogram|ECG]] in patients with [[hyperthyroidism | * However, the following findings may be seen on [[The electrocardiogram|ECG]] in patients with [[hyperthyroidism]] and [[thyrotoxicosis]]: | ||
**[[Sinus tachycardia]] | **[[Sinus tachycardia]] | ||
**[[Atrial fibrillation]] (often in [[elderly]] patients) | **[[Atrial fibrillation]] (often in [[elderly]] patients) | ||
Line 116: | Line 211: | ||
===X-ray=== | ===X-ray=== | ||
There are no x-ray findings associated with [[COVID-19]]-associated [[thyroid diseases]]. | * There are no x-ray findings associated with [[COVID-19]]-associated [[thyroid diseases]]. | ||
===Echocardiography or Ultrasound=== | ===Echocardiography or Ultrasound=== | ||
Line 127: | Line 222: | ||
===MRI=== | ===MRI=== | ||
There are no MRI findings associated with COVID-19-associated thyroid diseases. | * There are no MRI findings associated with COVID-19-associated thyroid diseases. | ||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
====Thyroid ultrasound==== | |||
*Thyroid ultrasound may help diagnose Graves's disease. Typically, the thyroid pattern in Graves' disease is hypoechoic. Thyroid ultrasound gives an accurate estimation of the thyroid size, which is important in planning the therapeutic management and allows the detection of thyroid nodules that may not be palpable on physical examination. | |||
====Color flow Doppler==== | |||
*Color flow Doppler (CFD) estimates the blood flow which, in hyperthyroid Graves' disease patients, is typically increased within the thyroid gland. | |||
*CFD can be useful in the differential diagnosis of Graves' disease and other causes of thyrotoxicosis characterized by a low blood flow to the thyroid, such as factitious thyrotoxicosis, painless and subacute thyroiditis. <ref name="pmid21663420">{{cite journal |vauthors=Kahaly GJ, Bartalena L, Hegedüs L |title=The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: a European perspective |journal=Thyroid |volume=21 |issue=6 |pages=585–91 |year=2011 |pmid=21663420 |doi=10.1089/thy.2011.2106.ed3 |url=}}</ref> | |||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
====Radioactive iodine uptake==== | ====Radioactive iodine uptake==== | ||
24-hr radioactive iodine uptake (RAIU) is a diagnostic measure for Graves' disease, which shows increased homogeneous uptake.<ref>{{Cite journal | * 24-hr [[radioactive iodine uptake]] ([[RAIU]]) is a diagnostic measure for [[Graves' disease]], which shows increased homogeneous uptake.<ref>{{Cite journal | ||
| author = [[Terry J. Smith]] & [[Laszlo Hegedus]] | | author = [[Terry J. Smith]] & [[Laszlo Hegedus]] | ||
| title = Graves' Disease | | title = Graves' Disease | ||
Line 149: | Line 246: | ||
| pmid = 27797318 | | pmid = 27797318 | ||
}}</ref> | }}</ref> | ||
*RAIU is generally increased in Graves' disease because of the action of stimulating TRAbs. | * [[RAIU]] is generally increased in [[Graves' disease]] because of the action of stimulating [[TRAbs]]. | ||
*Normal values for RAIU 24 h after the administration of a tracer dose of radioiodine are 20% in iodine sufficient and 40% in iodine deficient areas. | * Normal values for [[RAIU]] 24 h after the administration of a tracer dose of radioiodine are 20% in iodine sufficient and 40% in iodine-deficient areas. | ||
====Thyroid | {| style="border: 0px; font-size: 90%; margin: 3px;" align="center" | ||
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Thyroid Disease}} | |||
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|TSH receptor antibodies}} | |||
==== | ! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Thyroid Ultrasound}} | ||
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Color flow Doppler}} | |||
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Radioactive iodine uptake/Scan}} | |||
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Other features}} | |||
|- | |||
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Graves' disease}} | |||
| style="padding: 5px 5px; background: #F5F5F5;" | + | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Hypoechoic pattern | |||
| style="padding: 5px 5px; background: #F5F5F5;" | ↑ | |||
| style="padding: 5px 5px; background: #F5F5F5;" | ↑ | |||
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ophthalmopathy]], [[dermopathy]] | |||
|- | |||
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Toxic nodular goiter}} | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Multiple nodules | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Hot nodules at thyroid scan | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
|- | |||
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Toxic adenoma}} | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Single nodule | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Hot nodule | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
|- | |||
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Subacute thyroiditis}} | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Heterogeneous hypoechoic areas | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Reduced/absent flow | |||
| style="padding: 5px 5px; background: #F5F5F5;" | ↓ | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Neck pain, fever, and elevated inflammatory markers | |||
|- | |||
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Painless thyroiditis}} | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Hypoechoic pattern | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Reduced/absent flow | |||
| style="padding: 5px 5px; background: #F5F5F5;" | ↓ | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Symptoms and signs of [[hypothyroidism]] | |||
|- | |||
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hashimoto's thyroiditis}} | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Diffusely enlarged thyroid gland with a heterogeneous echotexture | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Normal | |||
| style="padding: 5px 5px; background: #F5F5F5;" | early stages: may show increased uptake, late stages: single or multiple areas of reduced uptake (cold spots) | |||
| style="padding: 5px 5px; background: #F5F5F5;" | - | |||
|} | |||
* To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].<br /> | * To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].<br /> | ||
Line 176: | Line 317: | ||
==References== | ==References== | ||
[[Category:Needs english review]] |
Latest revision as of 14:59, 17 August 2022
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2]
Overview
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus named for the similarity of its symptoms to those caused by the severe acute respiratory syndrome. Coronavirus disease 2019 (COVID-19) has been considered a global pandemic since its first emergence in Wuhan, China. On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.COVID-19 has been found to affect several organs and body systems, including the endocrine system, with short-term and possible long-term consequences. Recent data shows that COVID-19 patients have experienced a range of thyroid diseases.
Historical Perspective
- Coronavirus disease 2019 (COVID-19) has been considered as a global pandemic since its first emergence in Wuhan,China.[1]
- On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
- In March 2020, the first case of subacute thyroiditis in an 18-year-old woman with COVID-19 was described. [2]
Classification
There is no established system for the classification of COVID-19-associated thyroid disorders.
Pathophysiology
The exact pathogenesis of COVID-19-associated thyroid diseases is not fully understood. However, the following hypotheses have been suggested for the development of thyroid dysfunction in COVID-19 patients. [3] [4] [5] [6] [7] [8]
- Angiotensin-converting enzyme 2 (ACE2) receptors are essentially involved in SARS-CoV-2 internalization into host cells. The thyroid gland is amongst the organs which have the highest levels of ACE2 expression and activity. Therefore, following SARS-CoV-2 infection, thyroid damage could result from either a direct or immune-mediated injury.
- COVID-19 may also cause an immune system imbalance and, in severe cases, a cytokine storm, which may break immunotolerance in susceptible patients, leading to new onset of immune-mediated thyroiditis, exacerbating a previous thyroid disease, or inducing a recurrence of thyroid disease.
- The other potential pathophysiology for the development of thyroid disease in COVID-19 could be an underlying euthyroid sick syndrome, also known as nonthyroidal illness syndrome (NTIS), caused by critical illness. Patients with the euthyroid sick syndrome are often characterized by low T3 concentration, along with a normal or low serum TSH. T4 concentration may be low in more severe or prolonged illnesses.
- The fourth hypothesis is that hypothalamic-pituitary-thyroid (HPT) axis dysfunction in COVID-19 Patients results in a decresaed level of serum TSH in patients with SARS-CoV-2, causing secondary causes of hypothyroidism (central hypothyroidism).
Causes
Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called SARS-CoV-2 is the cause of COVID-19-associated thyroid diseases. To read more click here
Differentiating COVID-19-associated thyroid diseases from other Diseases
- Differential diagnosis of hyperthyroidism in COVID-19 patients may include: [2] [9] [10] [11] [12] [13] [14] [15] [15] [16] [2]
- Differential diagnosis of hypothyroidism in in COVID-19 patients may include:
- For a complete list of differential diagnoses of hyperthyroidism, please click here.
- For a complete list of differential diagnoses of hypothyroidism, please click here.
- For a complete list of differential diagnoses of the euthyroid sick syndrome, please click here.
Epidemiology and Demographics
- Data on the exact epidemiology and demographics of thyroid diseases in COVID-19 patients are lacking.
- Several cases of subacute thyroiditis, Hashimoto thyroiditis, myxedema coma, Grave's disease, atypical thyroiditis, thyrotoxicosis, sick euthyroid syndrome have been reported in COVID-19 patients worldwide. [2] [9] [10] [11] [12] [13] [14] [15] [15] [16] [2]
Risk Factors
There are no established risk factors for COVID-19-associated thyroid diseases.
Screening
There is insufficient evidence to recommend routine screening for COVID-19-associated thyroid diseases.
Natural History, Complications, and Prognosis
A number of observational studies have shown that COVID-19 infection may be linked to some thyroid diseases, including: [2] [9] [10] [11] [12] [13] [14] [15] [15] [16] [2]
- Subacute thyroiditis
- Graves’ disease
- Non-thyroidal illness or euthyroid sick syndrome
- Thyrotoxicosis
- Hashimoto’s thyroiditis
- Prognosis has generally been good in most cases of COVID-19 patients with hyperthyroidism/hypothyroidism.
- In a patient with subacute thyroiditis, the thyroid function and inflammatory markers normalized in 40 days. [2]
- In a study on 154 COVID-19 patients, Low fT3 (i.e., euthyroid sick syndrome) was associated with higher mortality and increased IL-6, suggesting poor prognosis in these patients. [17]
Diagnosis
Diagnostic Study of Choice
The diagnosis of COVID-19-associated thyroid diseases is made based on the thyroid function test (TFT), which measures serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH).
History and Symptoms
The symptoms of clinical hyperthyroidism in COVID-19 patients are similar to hyperthyroidism in the general population. The most common symptoms include:
The symptoms of clinical hypothyroidism in COVID-19 patients are similar to hypothyroidism in the general population. The most common symptoms include:
- Fatigue
- Cold intolerance
- Decreased sweating
- Hypothermia
- Coarse skin
- Weight gain
- Hoarseness
- Depression
- Emotional lability
- Attention deficit
- Puffiness
- Hair loss
- Constipation
- Slowed speech and movements
- Hyperlipidemia
- Galactorrhea
- Myxedema coma (with non-pitting edema)
If accompanied by thyroiditis:
Physical Examination
The most common physical examination findings in patients with hyperthyroidism include: [18]
- Tachycardia
- Stare
- Eyelid lag
- Resting tremor
- Hyperreflexia
- Warm, moist, and smooth skin
- In patients with Graves's disease:
- Localized dermopathy (i.e., pretibial myxedema)
- Proptosis (exophthalmos)
- Goiter
The most common physical examination findings in patients with hypothyroidism include:
- Myxedema: in patients with Hashimoto's thyroiditis
- Bradycardia
- Dry skin
- Coarse hair
- Enlarged thyroid gland or presence of goiter
- Small or shrunken thyroid gland (late in the disease)
- Bradypnea
- Slowed speech
- Slowed reflexes
Laboratory Findings
The laboratory findings in hyperthyroidism are:
- Elevated levels of serum thyroxine (T4) and triiodothyronine (T3).
- Undetectable serum TSH.
- Total T4 and T3 measurements are influenced by multiple conditions affecting serum thyroxine-binding globulin (TBG). Thus, the measurement of free thyroid hormones; free T4 (FT4) and free T3 (fT3), is the gold standard for the diagnosis of Graves' disease.[19]
- Antibodies against the TSH receptor (TRAbs) are pathognomonic for Graves' disease. They are detectable in the serum of about 98% of untreated patients.[20] Detection of TRAbs rules out other causes of thyrotoxicosis.[21]
- Anti-thyroid peroxidase (TPO) and antithyroglobulin (Tg) antibodies are also detectable in many patients with Graves' disease, but it is not recommended to measure these antibodies for diagnosis in all patients.
The laboratory findings in hypothyroidism are:
- Increased Thyroid-stimulating hormone (TSH)
- Decreased Free T3 and Free T4
- TSH may be decreased in the transient hyperthyroid state [22]
- Thyroid antibodies are usually positive in patients with Hashimoto's thyroiditis:
- Anti-thyroid peroxidase antibodies (anti-TPO) (correlates with the disease severity)
- Anti-thyroglobulin antibodies (anti-Tg)
- Anti-microsomal antibodies can help obtain an accurate diagnosis [23]
The laboratory findings in euthyroid sick syndrome are:
Euthyroid sick syndrome | T3
(80-180 ng/dl) |
T4
(4.6-12 ug/dl) |
FT4
(0.7-1.9 ng/dl) |
TSH
(0.4 to 4.0mIU/L) |
Reverse T3
(90 to 350pg/mL) |
---|---|---|---|---|---|
Mild euthyroid sick syndrome | ↓ | N | N | N | ↑ |
Moderate euthyroid sick syndrome | ↓ | N | N/↓ | N/↓ | ↑ |
Severe euthyroid sick syndrome | ↓ | ↓ | N/↓ | ↓ | ↑ |
Recovery | N/↓ | N | N | N | N/↑ |
Electrocardiogram
- There are no ECG findings associated with COVID-19-associated thyroid disease.
- However, the following findings may be seen on ECG in patients with hyperthyroidism and thyrotoxicosis:
- Sinus tachycardia
- Atrial fibrillation (often in elderly patients)
- Complete heart block (rare)
- Changes in QT interval
- The following findings may be seen on ECG in patients with hypothyroidism:
- Sinus bradycardia
- Prolonged QTc interval
- Changes in the morphology of the T-wave and QRS duration
- Low voltage.
X-ray
- There are no x-ray findings associated with COVID-19-associated thyroid diseases.
Echocardiography or Ultrasound
- There are no echocardiographyfindings associated with COVID-19-associated thyroid diseases.
- Thyroid ultrasoongraphy
CT scan
- There are no CT scan findings associated with COVID-19-associated thyroid diseases.
MRI
- There are no MRI findings associated with COVID-19-associated thyroid diseases.
Other Imaging Findings
Thyroid ultrasound
- Thyroid ultrasound may help diagnose Graves's disease. Typically, the thyroid pattern in Graves' disease is hypoechoic. Thyroid ultrasound gives an accurate estimation of the thyroid size, which is important in planning the therapeutic management and allows the detection of thyroid nodules that may not be palpable on physical examination.
Color flow Doppler
- Color flow Doppler (CFD) estimates the blood flow which, in hyperthyroid Graves' disease patients, is typically increased within the thyroid gland.
- CFD can be useful in the differential diagnosis of Graves' disease and other causes of thyrotoxicosis characterized by a low blood flow to the thyroid, such as factitious thyrotoxicosis, painless and subacute thyroiditis. [24]
Other Diagnostic Studies
Radioactive iodine uptake
- 24-hr radioactive iodine uptake (RAIU) is a diagnostic measure for Graves' disease, which shows increased homogeneous uptake.[25]
- RAIU is generally increased in Graves' disease because of the action of stimulating TRAbs.
- Normal values for RAIU 24 h after the administration of a tracer dose of radioiodine are 20% in iodine sufficient and 40% in iodine-deficient areas.
Thyroid Disease | TSH receptor antibodies | Thyroid Ultrasound | Color flow Doppler | Radioactive iodine uptake/Scan | Other features |
---|---|---|---|---|---|
Graves' disease | + | Hypoechoic pattern | ↑ | ↑ | Ophthalmopathy, dermopathy |
Toxic nodular goiter | - | Multiple nodules | - | Hot nodules at thyroid scan | - |
Toxic adenoma | - | Single nodule | - | Hot nodule | - |
Subacute thyroiditis | - | Heterogeneous hypoechoic areas | Reduced/absent flow | ↓ | Neck pain, fever, and elevated inflammatory markers |
Painless thyroiditis | - | Hypoechoic pattern | Reduced/absent flow | ↓ | Symptoms and signs of hypothyroidism |
Hashimoto's thyroiditis | - | Diffusely enlarged thyroid gland with a heterogeneous echotexture | Normal | early stages: may show increased uptake, late stages: single or multiple areas of reduced uptake (cold spots) | - |
- To view other diagnostic studies for COVID-19, click here.
Treatment
Medical Therapy
- Treatment of COVID-19-associated thyroid diseases generally depends on the presentation of thyroid disease.
- No specific treatment has been reported for COVID-19-associated thyroid disease.
Surgery
Surgery is not a treatment option for patients with COVID-19-associated thyroid diseases.
Primary Prevention
There are no established measures for the primary prevention of COVID-19-associated thyroid diseases.
Secondary Prevention
There are no established measures for the secondary prevention of COVID-19-associated thyroid diseases.
References
- ↑ "WHO Western Pacific | World Health Organization".
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F (2020). "Subacute Thyroiditis After Sars-COV-2 Infection". J Clin Endocrinol Metab. 105 (7). doi:10.1210/clinem/dgaa276. PMC 7314004 Check
|pmc=
value (help). PMID 32436948 Check|pmid=
value (help). - ↑ Lisco G, De Tullio A, Jirillo E, Giagulli VA, De Pergola G, Guastamacchia E; et al. (2021). "Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects". J Endocrinol Invest. 44 (9): 1801–1814. doi:10.1007/s40618-021-01554-z. PMC 7992516 Check
|pmc=
value (help). PMID 33765288 Check|pmid=
value (help). - ↑ Lazartigues E, Qadir MMF, Mauvais-Jarvis F (2020). "Endocrine Significance of SARS-CoV-2's Reliance on ACE2". Endocrinology. 161 (9). doi:10.1210/endocr/bqaa108. PMC 7454499 Check
|pmc=
value (help). PMID 32652001 Check|pmid=
value (help). - ↑ Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P (2021). "Impact of COVID-19 on the thyroid gland: an update". Rev Endocr Metab Disord. 22 (4): 803–815. doi:10.1007/s11154-020-09615-z. PMC 7688298 Check
|pmc=
value (help). PMID 33241508 Check|pmid=
value (help). - ↑ Fliers E, Bianco AC, Langouche L, Boelen A (2015). "Thyroid function in critically ill patients". Lancet Diabetes Endocrinol. 3 (10): 816–25. doi:10.1016/S2213-8587(15)00225-9. PMC 4979220. PMID 26071885.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID doi:10.1210/clinem/dgaa813 Check
|pmid=
value (help). - ↑ Leow MK, Kwek DS, Ng AW, Ong KC, Kaw GJ, Lee LS (2005). "Hypocortisolism in survivors of severe acute respiratory syndrome (SARS)". Clin Endocrinol (Oxf). 63 (2): 197–202. doi:10.1111/j.1365-2265.2005.02325.x. PMC 7188349 Check
|pmc=
value (help). PMID 16060914. - ↑ 9.0 9.1 9.2 Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ (2020). "Subacute thyroiditis associated with COVID-19". BMJ Case Rep. 13 (8). doi:10.1136/bcr-2020-237336. PMC 7449350 Check
|pmc=
value (help). PMID 32843467 Check|pmid=
value (help). - ↑ 10.0 10.1 10.2 Asfuroglu Kalkan E, Ates I (2020). "A case of subacute thyroiditis associated with Covid-19 infection". J Endocrinol Invest. 43 (8): 1173–1174. doi:10.1007/s40618-020-01316-3. PMC 7273820 Check
|pmc=
value (help). PMID 32504458 Check|pmid=
value (help). - ↑ 11.0 11.1 11.2 Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F; et al. (2020). "Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series". J Clin Endocrinol Metab. 105 (10). doi:10.1210/clinem/dgaa537. PMC 7454668 Check
|pmc=
value (help). PMID 32780854 Check|pmid=
value (help). - ↑ 12.0 12.1 12.2 Chakraborty U, Ghosh S, Chandra A, Ray AK (2020). "Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity". BMJ Case Rep. 13 (12). doi:10.1136/bcr-2020-239953. PMC 7750881 Check
|pmc=
value (help). PMID 33370933 Check|pmid=
value (help). - ↑ 13.0 13.1 13.2 Campos-Barrera E, Alvarez-Cisneros T, Davalos-Fuentes M (2020). "Subacute Thyroiditis Associated with COVID-19". Case Rep Endocrinol. 2020: 8891539. doi:10.1155/2020/8891539. PMC 7522602 Check
|pmc=
value (help). PMID 33005461 Check|pmid=
value (help). - ↑ 14.0 14.1 14.2 Tee LY, Harjanto S, Rosario BH (2021). "COVID-19 complicated by Hashimoto's thyroiditis". Singapore Med J. 62 (5): 265. doi:10.11622/smedj.2020106. PMC 8801861 Check
|pmc=
value (help). PMID 32668831 Check|pmid=
value (help). - ↑ 15.0 15.1 15.2 15.3 15.4 15.5 Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T; et al. (2020). "Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19". J Endocr Soc. 4 (10): bvaa130. doi:10.1210/jendso/bvaa130. PMC 7499619 Check
|pmc=
value (help). PMID 32984743 Check|pmid=
value (help). - ↑ 16.0 16.1 16.2 Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A; et al. (2020). "SARS-CoV-2-related atypical thyroiditis". Lancet Diabetes Endocrinol. 8 (9): 739–741. doi:10.1016/S2213-8587(20)30266-7. PMC 7392564 Check
|pmc=
value (help). PMID 32738929 Check|pmid=
value (help). - ↑ Dabas A, Singh H, Goswami B, Kumar K, Dubey A, Jhamb U; et al. (2021). "Thyroid Dysfunction in COVID-19". Indian J Endocrinol Metab. 25 (3): 198–201. doi:10.4103/ijem.ijem_195_21. PMC 8547402 Check
|pmc=
value (help). PMID 34760673 Check|pmid=
value (help). - ↑ Terry J. Smith & Laszlo Hegedus (2016). "Graves' Disease". The New England journal of medicine. 375 (16): 1552–1565. doi:10.1056/NEJMra1510030. PMID 27797318. Unknown parameter
|month=
ignored (help) - ↑ Dufour DR (2007). "Laboratory tests of thyroid function: uses and limitations". Endocrinol. Metab. Clin. North Am. 36 (3): 579–94, v. doi:10.1016/j.ecl.2007.04.003. PMID 17673120.
- ↑ Zöphel K, Roggenbuck D, Schott M (2010). "Clinical review about TRAb assay's history". Autoimmun Rev. 9 (10): 695–700. doi:10.1016/j.autrev.2010.05.021. PMID 20594972.
- ↑ Barbesino G, Tomer Y (2013). "Clinical review: Clinical utility of TSH receptor antibodies". J. Clin. Endocrinol. Metab. 98 (6): 2247–55. doi:10.1210/jc.2012-4309. PMC 3667257. PMID 23539719.
- ↑ Simmons, PJ (1998). "Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a role of interleukin-1beta and interleukin-6". Endocrinology. 139 (7): 3158–3186. doi:10.1210/en.139.7.3148. PMID 9645688.
- ↑ 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.
- ↑ Kahaly GJ, Bartalena L, Hegedüs L (2011). "The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: a European perspective". Thyroid. 21 (6): 585–91. doi:10.1089/thy.2011.2106.ed3. PMID 21663420.
- ↑ Terry J. Smith & Laszlo Hegedus (2016). "Graves' Disease". The New England journal of medicine. 375 (16): 1552–1565. doi:10.1056/NEJMra1510030. PMID 27797318. Unknown parameter
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ignored (help)