Thyrotoxicosis in patients with COVID-19: the THYRCOV study

in European Journal of Endocrinology
View More View Less
  • 1 Endocrinology, Diabetology and Medical Andrology Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
  • 2 Department of Biomedical Sciences, Humanitas University, Milan, Italy
  • 3 Laboratory Medicine, Humanitas Clinical and Research Center, IRCCS, Milan, Italy

Correspondence should be addressed to G Mazziotti; Email: gherardo.mazziotti@hunimed.eu
Restricted access

Objective:

This study assessed thyroid function in patients affected by the coronavirus disease-19 (COVID-19), based on the hypothesis that the cytokine storm associated with COVID-19 may influence thyroid function and/or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly act on thyroid cells, such as previously demonstrated for SARS-CoV-1 infection.

Design and methods:

This single-center study was retrospective and consisted in evaluating thyroid function tests and serum interleukin-6 (IL-6) values in 287 consecutive patients (193 males, median age: 66 years, range: 27–92) hospitalized for COVID-19 in non-intensive care units.

Results:

Fifty-eight patients (20.2%) were found with thyrotoxicosis (overt in 31 cases), 15 (5.2%) with hypothyroidism (overt in only 2 cases), and 214 (74.6%) with normal thyroid function. Serum thyrotropin (TSH) values were inversely correlated with age of patients (rho −0.27; P < 0.001) and IL-6 (rho −0.41; P < 0.001). In the multivariate analysis, thyrotoxicosis resulted to be significantly associated with higher IL-6 (odds ratio: 3.25, 95% confidence interval: 1.97–5.36; P < 0.001), whereas the association with age of patients was lost (P = 0.09).

Conclusions:

This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 885 885 885
Full Text Views 75 75 75
PDF Downloads 69 69 69
  • 1

    Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei C & Hui DSC Clinical characteristics of coronavirus disease 2019 in China. New England Journal of Medicine 2020 382 17081720. (https://doi.org/10.1056/NEJMoa2002032)

    • Search Google Scholar
    • Export Citation
  • 2

    Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: an emerging target of JAK2 inhibitor Fedratinib. Journal of Microbiology, Immunology, and Infection 2020 53 368370. (https://doi.org/10.1016/j.jmii.2020.03.005)

    • Search Google Scholar
    • Export Citation
  • 3

    Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pacific Journal of Allergy and Immunology 2020 38 19. (https://doi.org/10.12932/AP-200220-0772)

    • Search Google Scholar
    • Export Citation
  • 4

    Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, Wang J, Qin Y, Zhang X & Yan X The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clinical Immunology 2020 214 108393. (https://doi.org/10.1016/j.clim.2020.108393)

    • Search Google Scholar
    • Export Citation
  • 5

    Mazziotti G, Sorvillo F, Naclerio C, Farzati A, Cioffi M, Perna R, Valentini G, Farzati B, Amato G, Carella C. Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto’s thyroiditis. European Journal of Endocrinology 2003 148 383388. (https://doi.org/10.1530/eje.0.1480383)

    • Search Google Scholar
    • Export Citation
  • 6

    Mazziotti G, Sorvillo F, Piscopo M, Morisco F, Cioffi M, Stornaiuolo G, Gaeta GB, Molinari AM, Lazarus JH & Amato G Innate and acquired immune system in patients developing interferon-alpha-related autoimmune thyroiditis: a prospective study. Journal of Clinical Endocrinology and Metabolism 2005 90 41384144. (https://doi.org/10.1210/jc.2005-0093)

    • Search Google Scholar
    • Export Citation
  • 7

    Farzati B, Mazziotti G, Cuomo G, Ressa M, Sorvillo F, Amato G, La Montagna G, Carella C, Valentini G. Hashimoto’s thyroiditis is associated with peripheral lymphocyte activation in patients with systemic sclerosis. Clinical and Experimental Rheumatology 2005 23 4349.

    • Search Google Scholar
    • Export Citation
  • 8

    Kristensen B, Hegedus L, Madsen HO, Smith TJ, Nielsen CH. Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto’s thyroiditis. Clinical and Experimental Immunology 2015 180 5869. (https://doi.org/10.1111/cei.12557)

    • Search Google Scholar
    • Export Citation
  • 9

    Trovato M, Ruggeri RM, Sciacchitano S, Vicchio TM, Picerno I, Pellicano G, Valenti A, Visalli G. Serum interleukin-6 levels are increased in HIV-infected patients that develop autoimmune disease during long-term follow-up. Immunobiology 2018 223 264268. (https://doi.org/10.1016/j.imbio.2017.10.039)

    • Search Google Scholar
    • Export Citation
  • 10

    Bartalena L, Brogioni S, Grasso L, Martino E. Interleukin-6 and the thyroid. European Journal of Endocrinology 1995 132 386393. (https://doi.org/10.1530/eje.0.1320386)

    • Search Google Scholar
    • Export Citation
  • 11

    Leow MK, Kwek DS, Ng AW, Ong KC, Kaw GJ, Lee LS. Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). Clinical Endocrinology 2005 63 197202. (https://doi.org/10.1111/j.1365-2265.2005.02325.x)

    • Search Google Scholar
    • Export Citation
  • 12

    Wei L, Sun S, Xu CH, Zhang J, Xu Y, Zhu H, Peh SC, Korteweg C, McNutt MA, Gu J. Pathology of the thyroid in severe acute respiratory syndrome. Human Pathology 2007 38 95102. (https://doi.org/10.1016/j.humpath.2006.06.011)

    • Search Google Scholar
    • Export Citation
  • 13

    Spencer C, Eigen A, Shen D, Duda M, Qualls S, Weiss S, Nicoloff J. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clinical Chemistry 1987 33 13911396. (https://doi.org/10.1093/clinchem/33.8.1391)

    • Search Google Scholar
    • Export Citation
  • 14

    Rosenfarb J, Sforza N, Rujelman R, Morosan Allo Y, Parisi C, Blanc E, Frigerio C, Fossati P, Caruso D & Faingold C Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness. Journal of Endocrinological Investigation 2019 42 667671. (https://doi.org/10.1007/s40618-018-0967-0)

    • Search Google Scholar
    • Export Citation
  • 15

    Bashkin A, Yaakobi E, Nodelman M, Ronen O. Is routine measurement of TSH in hospitalized patients necessary? Endocrine Connections 2018 7 567572. (https://doi.org/10.1530/EC-18-0004)

    • Search Google Scholar
    • Export Citation
  • 16

    Wartofsky L, Burman KD. Alterations in thyroid function in patients with systemic illness: the ‘euthyroid sick syndrome’. Endocrine Reviews 1982 3 164217. (https://doi.org/10.1210/edrv-3-2-164)

    • Search Google Scholar
    • Export Citation
  • 17

    Carle A, Andersen SL, Boelaert K, Laurberg P. MANAGEMENT OF ENDOCRINE DISEASE: Subclinical thyrotoxicosis: prevalence, causes and choice of therapy. European Journal of Endocrinology 2017 176 R325R337. (https://doi.org/10.1530/EJE-16-0276)

    • Search Google Scholar
    • Export Citation
  • 18

    Scappaticcio L, Trimboli P, Keller F, Imperiali M, Piccardo A, Giovanella L. Diagnostic testing for Graves’ or non-Graves’ hyperthyroidism: a comparison of two thyrotropin receptor antibody immunoassays with thyroid scintigraphy and ultrasonography. Clinical Endocrinology 2020 92 169178. (https://doi.org/10.1111/cen.14130)

    • Search Google Scholar
    • Export Citation
  • 19

    Carella C, Mazziotti G, Amato G, Braverman LE, Roti E. Clinical review 169: interferon-alpha-related thyroid disease: pathophysiological, epidemiological, and clinical aspects. Journal of Clinical Endocrinology and Metabolism 2004 89 36563661. (https://doi.org/10.1210/jc.2004-0627)

    • Search Google Scholar
    • Export Citation
  • 20

    Iyer PC, Cabanillas ME, Waguespack SG, Hu MI, Thosani S, Lavis VR, Busaidy NL, Subudhi SK, Diab A, Dadu R. Immune-related thyroiditis with immune checkpoint inhibitors. Thyroid 2018 28 12431251. (https://doi.org/10.1089/thy.2018.0116)

    • Search Google Scholar
    • Export Citation
  • 21

    Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, Mou HM, Wang LH, Zhang HR & Fu WJ A pathological report of three COVID-19 cases by minimally invasive autopsies. Zhonghua Bing Li Xue Za Zhi 2020 49 E009.

    • Search Google Scholar
    • Export Citation
  • 22

    Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infectious Diseases of Poverty 2020 9 45. (https://doi.org/10.1186/s40249-020-00662-x)

    • Search Google Scholar
    • Export Citation
  • 23

    Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH & Nitsche A SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020 181 271.e8280.e8. (https://doi.org/10.1016/j.cell.2020.02.052)

    • Search Google Scholar
    • Export Citation
  • 24

    Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, Kucher N, Studt JD, Sacco C & Alexia B Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thrombosis Research 2020 191 914. (https://doi.org/10.1016/j.thromres.2020.04.024)

    • Search Google Scholar
    • Export Citation
  • 25

    Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020 395 473475. (https://doi.org/10.1016/S0140-6736(20)30317-2)

    • Search Google Scholar
    • Export Citation
  • 26

    Dekkers OM, Horvath-Puho E, Cannegieter SC, Vandenbroucke JP, Sorensen HT, Jorgensen JO. Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study. European Journal of Endocrinology 2017 176 19. (https://doi.org/10.1530/EJE-16-0576)

    • Search Google Scholar
    • Export Citation
  • 27

    Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, Cani DS, Cerini M, Farina D & Gavazi E Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiology 2020. (https://doi.org/10.1001/jamacardio.2020.1096)

    • Search Google Scholar
    • Export Citation
  • 28

    Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiology 2020 In pr. (https://doi.org/10.1001/jamacardio.2020.1286)

    • Search Google Scholar
    • Export Citation
  • 29

    Cho J, Afolabi B. Ventricular fibrillation associated with Graves’ disease and amiodarone induced thyrotoxicosis. Cardiovascular Endocrinology and Metabolism 2019 8 119124. (https://doi.org/10.1097/XCE.0000000000000184)

    • Search Google Scholar
    • Export Citation
  • 30

    Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best Practice and Research: Clinical Endocrinology and Metabolism 2013 27 745762. (https://doi.org/10.1016/j.beem.2013.10.003)

    • Search Google Scholar
    • Export Citation
  • 31

    Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ & HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020 395 10331034. (https://doi.org/10.1016/S0140-6736(20)30628-0)

    • Search Google Scholar
    • Export Citation
  • 32

    Minciullo PL, Ruggeri RM, Vita G, Benvenga S, Gangemi S. Development of Hashimoto’s thyroiditis after subacute thyroiditis: an unusual patient. Thyroid 2009 19 7374. (https://doi.org/10.1089/thy.2008.0234)

    • Search Google Scholar
    • Export Citation