COVID-19 and Endocrine System: A Cross-Sectional Study on 60 Patients with Endocrine Abnormality

Document Type : Original Article

Authors

1 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Ahar Bagher-al-Olum General Hospital, Ahar, Iran

3 Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Ira

4 Fertijin IVF Center Nispetiye Cad Bebek Yokusu Sokak, Etiler, Istanbul, Turkey

5 Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

6 Tabriz Imam Reza General Hospital, Tabriz, Iran

7 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Department of Tissue Engineering, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective: COVID-19 is an infectious disease that has become pandemic with a high mortality rate. This study aims to 
provide new insight into the relations between SARS-CoV-2 and the Endocrine system. 
Materials and Methods: In this cross-sectional study, we have hospitalized 60 patients with a positive SARA-CoV-2 PCR 
test. The information of complete blood count and endocrine hormones was obtained when the patients were admitted to the hospital or for a maximum of 4 days onset the hospitalization. 
Results: Of 60 patients with COVID-19, forty-four (73.33%) had at least one abnormality mean item >×3. In total, 26 (43.33%), 21 (35%), 18 (30%), 13 (21.67%), 31 (51.67%), 12 (20%), 30 (50%), 25 (41.67%) patients having estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, testosterone, cortisol and thyroid stimulating hormone (TSH) abnormal test results, respectively. There was no change in creatinine levels. FSH has shown drastic changes in both sexes’ intensity (F: 769, P<0.0001). Although TSH had many abnormalities in women, analysis has shown no significant P value (P=0.4558). Furthermore, prolactin and testosterone mean level in men and the estradiol mean level in women have shown no significant P value (P=0.2077, P=0.1446, P=0.1351, respectively). 
Conclusion: Results suggest that COVID-19 affects directly or non-directly glands and related hormones. 

Keywords


  1. Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). J Gen Intern Med. 2020; 35(5): 1545-1549.
  2. Drosten C, Günther S, Preiser W, Van Der Werf S, Brodt HR, Becker S, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20): 1967-1976.
  3. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012; 367(19): 1814-1820.
  4. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798): 265-269.
  5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497-506.
  6. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72314 cases from the chinese center for disease control and prevention. JAMA. 2020; 323(13): 1239-1242.
  7. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270-273. 8. Dimitrov DS. The secret life of ACE2 as a receptor for the SARS virus. Cell. 2003; 115(6): 652-653.
  8. Gui M, Song W, Zhou H, Xu J, Chen S, Xiang Y, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 2017; 27(1): 119-129.
  9. Song W, Gui M, Wang X, XiangY. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. 2018; 14(8): e1007236.
  10. Kirchdoerfer RN, Wang N, Pallesen J, Wrapp D, Turner HL, Cottrell CA, et al. Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis. Sci Rep. 2018; 8(1): 15701.
  11. Yuan Y, Cao D, Zhang Y, Ma J, Qi J, Wang Q, et al. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun. 2017; 8: 15092.
  12. Struck AW, Axmann M, Pfefferle S, Drosten C, Meyer B. A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2. Antiviral Res. 2012; 94(3): 288-296.
  13. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000; 87(5): E1-9.
  14. Prabakaran P, Xiao X, Dimitrov DS. A model of the ACE2 structure and function as a SARS-CoV receptor. Biochem Biophys Res Commun. 2004; 314(1): 235-241.
  15. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12(1): 8.
  16. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020; 14(2): 185-192.
  17. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell rna expression profiling of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020; 202(5): 756-759.
  18. Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. Gut. 2020; 69: 1010-1018.
  19. Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019- nCoV infection. bioRxiv. 2020.
  20. Fan C, Lu W, Li K, Ding Y, Wang J. ACE2 expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front Med (Lausanne). 2021; 7: 563893.
  21. Marazuela M, Giustina A, Puig-Domingo M. Endocrine and metabolic aspects of the COVID-19 pandemic. Rev Endocr Metab Disord. 2020; 21(4): 495-507.
  22. World Health Organization. Clinical management of severe acute respiratory infection ( SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. World Health Organization; 2020. Available from: https://apps.who.int/iris/handle/10665/331446 (12 March 2022).
  23. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious diseases society of america/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 Suppl 2: S27-S72.
  24. Oliveira FR, Ferreira JR, dos Santos CM, Macêdo LE, de Oliveira RB, Rodrigues JA, et al. Estradiol reduces cumulative mercury and associated disturbances in the hypothalamus-pituitary axis of ovariectomized rats. Ecotoxicol Environ Saf. 2006; 63(3): 488-493.
  25. Tanaka T, Utsunomiya T, Utsunomiya H, Umesaki N. Irinotecan HCl, an anticancer topoisomerase I inhibitor, frequently induces ovarian failure in premenopausal and perimenopausal women. Oncol Rep. 2008; 19(5): 1123-1133.
  26. Collins P, Rosano GM, Sarrel PM, Ulrich L, Adamopoulos S, Beale CM, et al. 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. 1995; 92(1): 24-30.
  27. Antus B, Hamar P, Kokeny G, Szollosi Z, Mucsi I, Nemes Z, et al. Estradiol is nephroprotective in the rat remnant kidney. Nephrol Dial Transplant. 2003; 18(1): 54-61.
  28. Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA, et al. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab. 2006; 91(10): 3908-3915.
  29. Wolf OT, Kudielka BM, Hellhammer DH, Törber S, McEwen BS, Kirschbaum C. Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels. Psychoneuroendocrinology. 1999; 24(7): 727-741.
  30. Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Williams DC, et al. 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest. 1992; 89(3): 883-891.
  31. LoRusso PM, Piha-Paul SA, Mita M, Colevas AD, Malhi V, Colburn D, et al. Co-administration of vismodegib with rosiglitazone or combined oral contraceptive in patients with locally advanced or metastatic solid tumors: a pharmacokinetic assessment of drugdrug interaction potential. Cancer Chemother Pharmacol. 2013; 71(1): 193-202.
  32. Boccabella AV, Alger EA. Influence of estradiol on thyroid: serum radioiodide concentration ratios of gonadectomized and hypophysectomized rats. Endocrinology. 1964; 74: 680-688.
  33. Bagot CN, Leishman E, Onyiaodike CC, Jordan F, Gibson VB, Freeman DJ. Changes in laboratory markers of thrombotic risk early in the first trimester of pregnancy may be linked to an increase in estradiol and progesterone. Thromb Res. 2019; 178: 47-53.
  34. Hu J, Lin JH, Jiménez MC, Manson JE, Hankinson SE, Rexrode KM. Plasma estradiol and testosterone levels and ischemic stroke in postmenopausal women. Stroke. 2020; 51(4): 1297-1300.
  35. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol–progestogen therapy. Obstet Gynecol. 2009; 113: 65-73.
  36. Oettel M, Mukhopadhyay AK. Progesterone: the forgotten hormone in men? Aging Male. 2004; 7(3): 236-257.
  37. Guennoun R, Labombarda F, Gonzalez Deniselle MC, Liere P, De Nicola AF, Schumacher M. Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection. J Steroid Biochem Mol Biol. 2015; 146: 48-61.
  38. Xiong F, Zhang L. Role of the hypothalamic-pituitary-adrenal axis in developmental programming of health and disease. Front Neuroendocrinol. 2013; 34(1): 27-46.