Covid-19 ve Tiroid
Özet
Bu çalışma, SARS-CoV-2 enfeksiyonunun tiroid bezi ve hipotalamik-hipofiz-tiroid (HHT) aksı üzerindeki doğrudan ve dolaylı etkilerini kapsamlı bir şekilde incelemektedir. Akciğerlere kıyasla tiroid dokusunda daha yüksek oranda eksprese edilen ACE2 ve TMPRSS2 reseptörleri, tiroidi virüs için açık bir hedef haline getirmektedir. COVID-19 seyrinde hastalarda tirotoksikoz, hipotiroidizm, atipik subakut tiroidit ve tiroid dışı hastalık sendromu (ötiroid hasta sendromu) gibi çeşitli fonksiyonel bozukluklar gözlenmektedir. Özellikle yoğun bakım hastalarında proinflamatuar sitokin fırtınasına (IL-6 vb.) ve viral sitopatik etkilere bağlı olarak düşük TSH ve T3 seviyeleriyle karakterize tablolar gelişebilmektedir. COVID-19 döneminde hipotiroidi yönetimi rutin replasman tedavisiyle devam ederken, hipertiroidi hastalarında antitiroid ilaçların (ATİ) neden olabileceği nadir ancak tehlikeli bir yan etki olan agranülositoz semptomları ile COVID-19'un ateş ve boğaz ağrısı gibi semptomları örtüşebilmektedir. Bu durumda ATİ tedavisinin acilen kesilerek tam kan sayımı yapılması önerilmektedir. Sonuç olarak, tiroid disfonksiyonu COVID-19 hastalarında klinik seyrin ve mortalite oranlarının kötüleşmesiyle ilişkili bulunmuştur.
This study comprehensively examines the direct and indirect impacts of SARS-CoV-2 infection on the thyroid gland and the hypothalamic-pituitary-thyroid (HPT) axis. The high expression of ACE2 and TMPRSS2 receptors in thyroid tissue makes it a direct target for the virus. Various functional disorders, including thyrotoxicosis, hypothyroidism, atypical subacute thyroiditis, and non-thyroidal illness syndrome, are frequently observed during the course of COVID-19. Particularly in critically ill patients, a profound cytokine storm (involving IL-6) and direct viral cytopathic actions can induce suppressed TSH and T3 levels. While the management of hypothyroidism remains standard during the pandemic, hyperthyroid patients face a diagnostic challenge: the symptoms of antithyroid drug (ATD)-induced agranulocytosis overlap with COVID-19 manifestations like fever and sore throat. In such instances, immediate cessation of ATD therapy and an urgent complete blood count are strongly recommended. Ultimately, the data indicates that underlying or newly developed thyroid dysfunction significantly correlates with poorer clinical outcomes, longer hospital stays, and increased mortality rates in COVID-19 patients.
Referanslar
World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19- 11 March 2020. Available online at https://www.who.int/dg/ speeches/detail/who-director-general-s-opening-remarksat-the-media-briefing-on-COVID-19---11-march-2020, Accessed date: 28.12.2021
Young MJ, Clyne CD, Chapman KE. Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2. The Journal of endocrinology, 2020;247(2): R45–R62. Doi.org/10.1530/JOE-20-0260
Pal R, Banerjee M (2020). COVID-19 and the endocrine system: exploring the unexplored. Journal of endocrinological investigation, 2020; 43(7): 1027–1031. Doi.org/10.1007/s40618-020-01276-8
Ersoy CÖ. COVID-19 ve endokrin Sistem Hastalıkları. İç: Heper C, ed. Bursa Tabip Odası Sürekli Tıp Eğitimi Pandemi Kitabı Temmuz 2020, multidisipliner COVID-19. Bursa: Stüdyo Star Ajans Ltd Şti; 2020: 407-27
Wei L, Sun S, Xu CH, et al. Pathology of the thyroid in severe acute respiratory syndrome. Human pathology, 2007;38(1): 95–102. Doi.org/10.1016/j.humpath.2006.06.011
Ding Y, He L, Zhang Q, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. The Journal of pathology, 2004;203(2): 622–630. Doi.org/10.1002/path.1560
Wei L, Sun S, Zhang J, et al. Endocrine cells of the adenohypophysis in severe acute respiratory syndrome (SARS). Biochemistry and cell biology = Biochimie et biologie cellulaire, 88(4): 723–730. Doi.org/10.1139/O10-022
Li H, Liu SM, Yu XH, et al. (2020). Coronavirus disease 2019 (COVID-19): current status and future perspectives. International journal of antimicrobial agents, 55(5):105951. Doi.org/10.1016/j.ijantimicag.2020.105951
Van den Berghe G. (2014). Non-thyroidal illness in the ICU: a syndrome with different faces. Thyroid: official journal of the American Thyroid Association, 24(10):1456–1465. Doi.org/10.1089/thy.2014.0201
Samuels MH (Effects of variations in physiological cortisol levels on thyrotropin secretion in subjects with adrenal insufficiency: a clinical research center study. The Journal of clinical endocrinology and metabolism, 2000;85(4): 1388–1393. Doi.org/10.1210/jcem.85.4.6540
Chen M, Zhou W, Xu W. Thyroid Function Analysis in 50 Patients with COVID-19: A Retrospective Study. Thyroid : official journal of the American Thyroid Association, 31(1): 8–11. https://doi.org/10.1089/thy.2020.0363
Tan T, Khoo B, Mills EG, et al. Association between high serum total cortisol concentrations and mortality from COVID-19. The lancet. Diabetes & endocrinology, (2020);8(8):659–660. Doi.org/10.1016/S2213-8587(20)30216-3
Lazartigues E, Qadir MMF, Mauvais-Jarvis F. Endocrine Significance of SARS-CoV-2's Reliance on ACE2. Endocrinology, 2020; 161(9): bqaa108. Doi.org/10.1210/endocr/bqaa108
Gavriatopoulou M, Korompoki E, Fotiou D, et al. Organ-specific manifestations of COVID-19 infection. Clinical and experimental medicine, 20(4): 493–506. Doi.org/10.1007/s10238-020-00648-x
Khoo B, Tan T, Clarke SA, et al. Thyroid Func¬tion Before, During, and After COVID-19. J Clin Endocrinol Metab. 2021; 23:106(2):e803-e811. Doi: 10.1210/clinem/dgaa830
Pashkovska NV. Pseudothyroid dysfunction in clini¬cal practice: how to avoid diagnostic errors. Mìžnarodnij endokri¬nologìčnij žurnal.2018;14(4):344-353. Doi:10.22141/2224 0721.14.4.2018.140188
Yao XH, Li TY, He ZC, et al. Zhonghua bing li xue za zhi = Chinese journal of pathology, 2020; 49(5): 411–417. https://doi.org/10.3760/cma.j.cn112151-20200312-00193
Hanley B, Naresh KN, Roufosse C,et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. The Lancet. Microbe, 2020; 1(6): e245–e253. https://doi.org/10.1016/S2666-5247(20)30115-4
Muller I, Cannavaro D, Dazzi D, et al. SARS-CoV-2-related atypical thyroiditis. The lancet. Diabetes & endocrinology, 2020;8(9):739–741. Doi.org/10.1016/S2213-8587(20)30266-7
Brancatella A, Ricci D, Cappellani D, et al. Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infec-tion? Insights From a Case Series. J Clin Endocrinol Metab. 2020; 1;105(10): dgaa537. Doi: 10.1210/clinem/dgaa537
Mattar S, Koh S, Rama Chandran S, et al Subacute thyroiditis associated with COVID-19. BMJ case reports, 2020; 13(8): e237336. Doi.org/10.1136/bcr-2020-237336
Lania, A, Sandri MT, Cellini M, et al Thyrotoxicosis in patients with COVID-19: the THYRCOV study. European journal of endocrinology, 2020; 183(4); 381–387. Doi.org/10.1530/EJE-20-0335
Ruggeri RM, Campennì A, Deandreis D, et al SARS-COV-2-related immune inflammatory thyroid disorders: facts and perspectives. Expert review of clinical immunology, 2021; 17(7), 737–759. Doi.org/10.1080/1744666X.2021.1932467
24.Pal R COVID-19, hypothalamo-pituitary-adrenal axis and clinical implications. Endocrine, 2020; 68(2): 251–252. Doi.org/10.1007/s12020-020-02325-1
Antonelli A, Ferrari SM, Ragusa F, et al. Graves' disease: Epidemiology, genetic and environmental risk factors and viruses. Best practice & research. Clinical endocrinology & metabolism, 2020;34(1): 101387. Doi.org/10.1016/j.beem.2020.101387
Chen T, Wu D, Chen H, et al (2020). Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ (Clinical research ed.), 368:m1091. Doi.org/10.1136/bmj.m1091
Pearce EN, Farwell AP, Braverman LE (2003). Thyroiditis. The New England journal of medicine, 348(26), 2646–2655. Doi.org/10.1056/NEJMra021194
Desailloud R, Hober D. Viruses and thyroiditis: an update. Virology journal, 2009;6: 5. Doi.org/10.1186/1743-422X-6-5
Marazuela M, Giustina A, Puig-Domingo M. Endocrine and metabolic aspects of the COVID-19 pandemic. Reviews in endocrine & metabolic disorders, 2020;21(4):495–507. Doi.org/10.1007/s11154-020-09569-2
Lisco G, De Tullio A, Stragapede A, et al. COVID-19 and the Endocrine System: A Comprehensive Review on the Theme. Journal of clinical medicine, 2021;10(13):2920. Doi.org/10.3390/jcm10132920
Şahin Tekin M, Şaylısoy S, Yorulmaz G. Subacute thyroiditis following COVID-19 vaccination in a 67-year-old male patient: a case report. Human vaccines & immunotherapeutics, 2021;17(11): 4090–4092. Doi.org/10.1080/21645515.2021.1947102
Scappaticcio L, Pitoian F, Esposito K, et al. Impact of COVID-19 on the thyroid gland: an update. Reviews in endocrine & metabolic disorders, 2021;22(4):803–815. Doi.org/10.1007/s11154-020-09615-z
Hamburger JI. Subacute thyroiditis: diagnostic difficulties and simple treatment. Journal of nuclear medicine : official publication, Society of Nuclear Medicine,1974; 15(2): 81–89
Dhakal BP, Sweitzer NK, Indik JH, et al. SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart. Heart, lung & circulation, 2020;29(7):973–987. Doi.org/10.1016/j.hlc.2020.05.101
Ruggeri RM, Campennì A, Siracusa M, et al. Subacute thyroiditis in a patient infected with SARS-COV-2: an endocrine complication linked to the COVID-19 pandemic. Hormones (Athens, Greece), 2021;20(1): 219–221. Doi.org/10.1007/s42000-020-00230-w
Hariyanto TI, Kurniawan A. Thyroid disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Diabetes & metabolic syndrome, 2020;14(5):1429–1430. Doi.org/10.1016/j.dsx.2020.07.044
Mateu-Salat, M., Urgell E, Chico A. SARS-COV-2 as a trigger for autoimmune disease: report of two cases of Graves' disease after COVID-19. Journal of endocrinological investigation, 2020;43(10):1527–1528. Doi.org/10.1007/s40618-020-01366-7
Marazuela M, Giustina A, Puig-Domingo M. Endocrine and metabolic aspects of the COVID-19 pandemic. Reviews in endocrine & metabolic disorders,2020; 21(4):495–507. Doi.org/10.1007/s11154-020-09569-2
Tee LY, Harjanto S, Rosario BH. COVID-19 complicated by Hashimoto's thyroiditis. Singapore medical journal,2021; 62(5): 265. Doi.org/10.11622/smedj.2020106
Persani L, Brabant G, Dattani M, et al. 2018 European Thyroid Association (ETA) guidelines on the diagnosis and management of central hypothyroidism. Eur Thyroid J. 2018;7(5):225–37. Doi.org/10.1159/000491388.
de Vries EM, Fliers E, Boelen A. The molecular basis of the non-thyroidal illness syndrome. The Journal of endocrinology, 2015;225(3):R67–R81. Doi.org/10.1530/JOE-15-0133
Fliers E, Bianco AC, Langouche L, et al. Thyroid function in critically ill patients. The lancet. Diabetes & endocrinology,2015; 3(10): 816–825. Doi.org/10.1016/S2213-8587(15)00225-9
Van den Berghe G. Non-thyroidal illness in the ICU: a syndrome with different faces. Thyroid : official journal of the American Thyroid Association, 2014;24(10):1456–1465. Doi.org/10.1089/thy.2014.0201
Li, T, Wang L, Wang H, et al. Characteristics of laboratory indexes in COVID-19 patients with non-severe symptoms in Hefei City, China: diagnostic value in organ injuries. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2020;39(12): 2447–2455. Doi.org/10.1007/s10096-020-03967-9
Li MY, Li L, Zhang Y,et al. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infectious diseases of poverty,2020; 9(1):45. Doi.org/10.1186/s40249-020-00662-x
Dai M, Liu D, Liu M, et al. Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak. Cancer discovery, 2020;10(6):783–791. Doi.org/10.1158/2159-8290.CD-20-0422
Tsang V, Gild,M, Glover A, et al. Thyroid cancer in the age of COVID-19. Endocrine-related cancer,2020; 27(11): R407–R416. Doi.org/10.1530/ERC-20-027
Smulever A, Abelleira E, Bueno F, et al. Thyroid cancer in the Era of COVID-19. Endocrine,2020; 70(1): 1–5. Doi.org/10.1007/s12020-020-02439-6
Coperchini F, Chiovato L, Croce L, et al. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine & growth factor reviews,2020; 53: 25–32. Doi.org/10.1016/j.cytogfr.2020.05.003
Java A, Apicelli AJ, Liszewski MK, et al. The complement system in COVID-19: friend and foe?. JCI insight, 2020;5(15): e140711. Doi.org/10.1172/jci.insight.140711
Boelaert K, Visser WE, Taylor PN, et al. ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of hyperthyroidism and hypothyroidism. European journal of endocrinology, 2020;183(1):G33–G39. Doi.org/10.1530/EJE-20-0445
De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet (London, England),2016; 388(10047): 906–918. Doi.org/10.1016/S0140-6736(16)00278-6
Chaker L, Bianco AC, Jonklaas et al. Hypothyroidism. Lancet (London, England), 2017;390(10101): 1550–1562. Doi.org/10.1016/S0140-6736(17)30703-1
Léger, J, Olivieri A, Donaldson M., et al. ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE, & Congenital Hypothyroidism Consensus Conference Group. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. The Journal of clinical endocrinology and metabolism, 2014;99(2):363–384. Doi.org/10.1210/jc.2013-1891
Burch HB, Cooper DS. ANNIVERSARY REVIEW: Antithyroid drug therapy: 70 years later. European journal of endocrinology,2018; 179(5): R261–R274. Doi.org/10.1530/EJE-18-0678
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England), 2020;395(10229),: 1054–1062. Doi.org/10.1016/S0140-6736(20)30566-3
Ross DS, Burch HB, Cooper DS, et al. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid : official journal of the American Thyroid Association, 2016;26(10):1343–1421. Doi.org/10.1089/thy.2016.0229
Terpos E, Ntanasis-Stathopoulos I., Elalamy I, et al. Hematological findings and complications of COVID-19. American journal of hematology, 2020;95(7):834–847. Doi.org/10.1002/ajh.25829
Taylor PN, Zhang L, Lee R, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nature reviews. Endocrinology, 2020;16(2):104–116. Doi.org/10.1038/s41574-019-0305-4
Kahaly GJ, Bartalena L, Hegedüs L,et al. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. European thyroid journal,2018;7(4):167–186. Doi.org/10.1159/000490384
Xia J, Tong J, Liu M.,et al. (2020). Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. Journal of medical virology,2020; 92(6):589–594. Doi.org/10.1002/jmv.25725
