The General Endocrine Picture of COVID-19 Infection: History
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Mara Carsote

From an endocrinological point of view, a high risk of severe COVID-19 infection is related to the presence of diabetes mellitus, high blood pressure, obesity, Cushing’s syndrome, sleep apnea (associated with acromegaly or obesity), coagulation anomalies, glucocorticoid therapy for various conditions, etc.. Hypocortisolemia may develop on immune grounds (in addition or not to primary/secondary hypothyroidism) due to direct or immune-mediated pituitary and adrenal lesions.

  • endocrine
  • COVID-19 infection
  • thyroid
  • thyroiditis
  • subacute

1. The General Endocrine Picture of COVID-19 Infection

Subacute thyroiditis (SAT) is part of the large, heterogeneous endocrine picture described in relation to the COVID-19 infection. From an endocrinological point of view, a high risk of severe COVID-19 infection is related to the presence of diabetes mellitus, high blood pressure, obesity, Cushing’s syndrome, sleep apnea (associated with acromegaly or obesity), coagulation anomalies, glucocorticoid therapy for various conditions, etc. [1][2]. Hypocortisolemia may develop on immune grounds (in addition or not to primary/secondary hypothyroidism) due to direct or immune-mediated pituitary and adrenal lesions [3]. Recently, the potential involvement of adrenal dysfunction (following or not following prior infection-related glucocorticoid exposure) was connected with long COVID-19 syndrome [4][5]. Also, transitory impairment of spermatogenesis in males, relative and direct hypoparathyroidism, and the worsening of metabolic bone disease have also been reported in subjects experiencing SARS-CoV-2 infection [6][7][8].

2. Thyroid Workup among COVID-19 Positive Patients: Where Do We Place Subacute Thyroiditis?

Suspecting or confirming SAT in patients infected with coronavirus represents a small piece of an otherwise very complex puzzle of the thyroid’s involvement under these specific circumstances [9]. Generally, the patient with prior thyroid disease is not considered to be at a high risk of contracting COVID-19 infection, nor of developing SAT secondary to coronavirus infection or after vaccination against the virus. Recently, it was found that uncontrolled hypothyroidism rather than hyperthyroidism is more prone to developing a severe form of COVID-19 infection, especially when associated with older age (although not all authors agree), thus thyroid–COVID-19 interplay might be more complex [10][11].
It is already known that any kind of infection, including coronavirus infection, may trigger hyperthyroidism that can manifest in various ways, including severe forms like thyroid storm, and needs to be differentiated from SAT-related transitory hyperthyroidism [12][13]. The direct thyroid injury caused by the virus leads to destructive thyroiditis that is usually associated with severe circumstances such as increased cytokine pathway activation [14]. Here did not include in this content any cases with this particular type of thyroiditis. Low-T3 syndrome has been found in severely ill patients and represents a predictor for poor outcomes in individuals infected with the SARS-CoV-2 virus; SAT should be differentiated from euthyroid sick syndrome (a differential diagnosis which is easier to perform in the following weeks after coronavirus infection rather than during infection) [15][16]. On the other hand, some cases of COVID-19-related thyroiditis have been retrospectively diagnosed based on current low thyroid hormone status in patients without a prior thyroid history. It is therefore important to consider it not only as a new SAT entity but also as a new approach to the differential diagnosis of hypothyroidism amid the COVID-19 pandemic.
Some authors have suggested that the COVID-19 infection might trigger the autoimmune mechanisms underlying Hashimoto’s thyroiditis (which is traditionally connected to a large area of other endocrine and non-endocrine autoimmune diseases) [17][18][19]. Also, aggravating selenium deficiency through the infection may act as a precipitating element [20]. Currently, there is not enough statistical evidence to support this specific hypothesis despite the theoretical rationale [21][22]. Other autoimmune complications in COVID-19-positive patients also include thrombocytopenia, hemolytic anemia, Guillan-Barre syndrome, etc. [23][24][25].
The rate of hypothyroidism in coronavirus-positive patients varies from study to study by up to one-fifth, and the underlying mechanisms are mostly represented by low-T3 syndrome as well as hypophysitis-related hypothyroidism, destructive thyroiditis, primary autoimmune hypothyroidism, residual thyroid insufficiency after an episode of SAT, etc. [26]. The thyroid hormone profile in severe cases might be regarded as a surrogate prognosis tool in patients without prior thyroid conditions, according to some authors despite not being generally recognized [27][28][29]. I should also take note of patients on anti-thyroid drugs or treated with high doses of radioiodine therapy for differentiated thyroid cancer, who may find themselves in a situation with an increased risk for neutropenia and agranulocytosis, thus aggravating any type of infection; also, SAT-associated temporary excess of thyroid hormones should be differentiated from primary hyperthyroidism in order to avoid unnecessary exposure to anti-thyroid drugs [30][31]. More aggressive forms of thyroid cancer during the COVID-19 pandemic era have been suggested to be caused by the delays in evaluation and surgical treatment due to lockdown restrictions and pandemic regulations that have bottlenecked access to medical services [32][33]. The rate of thyroidectomy access for benign goiter was found by some authors to be reduced during periods where restrictions were in place [34][35]. Similarly, the extensive use of telemedicine amid the pandemic might delay the presentation of SAT. Patients with previous thyroid nodules do not appear to be at greater risk during COVID-19 infection, nor at greater risk of developing a subacute complication of the thyroid, according to what has been described so far in the literature, [36][37].

3. Endocrine Conditions and Vaccination against COVID-19 Infection

A highly debated topic in the scientific community relates to the potential events involving COVID-19 immunization, including endocrine elements. It has been suggested that vaccination might aggravate eye disease or primary hyperthyroidism in patients with a history of Basedow–Graves disease. However, the level of statistical evidence remains poor up to this moment, and currently, the most probable pathogenic link is post-vaccine increased immunogenicity (including autoimmunity exacerbation and molecular mimicry), probably in susceptible individuals, although this has yet to be determined [38][39][40]. Primary hyper functioning of the thyroid needs a clear differentiation from the transitory hyperthyroidism underlying a subacute inflammation of the gland in order to avoid anti-thyroid medication. Hypophysitis with the clinical and hormonal expression of hypopituitarism was also reported (the level of statistical evidence, however, is of case reports) [41]. Immune- and/or inflammatory-mediated endocrine elements that have developed after COVID-19 vaccination may be regarded as a part of ASIA syndrome (it has been discussed whether Graves disease is a part of the syndrome), and the risk of exacerbating the autoimmune response by the infection itself has previously been described [42][43].
Generally, it can be considered that vaccination against COVID-19 is not associated with particular risks in patients with prior diagnoses of different endocrine conditions. Some diseases like diabetes mellitus and adrenal insufficiency have a particular indication for vaccine prioritization due to the higher risk of infections and more severe SARS-CoV-2 evolution [44][45]. Whether SAT might follow vaccination is still an open issue; the level of current statistical evidence is low but, as many other conditions amid the pandemic, the importance of awareness comes first at this point.
Whether symptoms of SAT after a certain vaccine dose should delay the following vaccine administration is debatable and, for the moment, there is no any particular concerns regarding protocols for immunization (but, of course, the vaccination started in 2021, so this is a limited period of time to be able to draw clear conclusions). There is only one longitudinal study, published in 2022, which included 15 cases with vaccine-associated thyroiditis of the subacute type, occurring a median of 11.5 days after immunization and a median remission time of 11.5 weeks; seven out of nine individuals were re-vaccinated and did not experience a relapse of subacute thyroiditis, while two out of nine individuals suffered an aggravation of SAT due to the second dose of the vaccine inoculation [46]. According to what people currently know, revaccination should not be restricted in patients who experienced SAT following any dose during immunization.
Overall, it can be recognized that the number of reported cases considering this new entity is low when compared with the millions of people that have had the coronavirus infection and received the vaccine, but many other unexpected novel clinical entities have been reported amid the pandemic at first with a low level of statistical evidence since the COVID-19 pandemic is an extraordinary, never-before-seen medical experience. This is why the lack of adequate recognition and diagnosis represents one more reason to spread the information and increase awareness in order to reduce disease-related burden if adequately recognized (including unnecessary investigations or medications) and to apply optimum health care for improved quality of life in affected patients. It's well to know, this is the largest number of patients with either COVID-19-related or vaccine-associated SAT to date

This entry is adapted from the peer-reviewed paper 10.3390/diagnostics12040960

References

  1. Jara, L.J.; López-Zamora, B.; Ordoñez-González, I.; Galaviz-Sánchez, M.F.; Gutierrez-Melgarejo, C.I.; Saavedra, M.; Vera-Lastra, O.; Cruz-Domínguez, M.P.; Medina, G. The immune-neuroendocrine system in COVID-19, advanced age and rheumatic diseases. Autoimmun. Rev. 2021, 20, 102946.
  2. Mung, S.M.; Jude, E.B. Interplay between endocrinology, metabolism and COVID-19 infection. Clin. Med. 2021, 21, e499–e504.
  3. Ilera, V.; Delfino, L.C.; Zunino, A.; Glikman, P.; Drnovsek, M.; Reyes, A.; Dios, A.; Toibaro, J.; Pachioli, V.; Lannes, N.; et al. Correlation between inflammatory parameters and pituitary–thyroid axis in patients with COVID-19. Endocrine 2021, 74, 455–460.
  4. Salzano, C.; Saracino, G.; Cardillo, G. Possible Adrenal Involvement in Long COVID Syndrome. Medicina 2021, 57, 1087.
  5. Lui, D.T.W.; Lee, C.H.; Chow, W.S.; Lee, A.C.H.; Tam, A.R.; Pang, P.; Ho, T.Y.; Fong, C.H.Y.; Law, C.Y.; Leung, E.K.H.; et al. Long COVID in Patients with Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role? Endocr. Pract. 2021, 27, 894–902.
  6. Kazakou, P.; Paschou, S.A.; Psaltopoulou, T.; Gavriatopoulou, M.; Korompoki, E.; Stefanaki, K.; Kanouta, F.; Kassi, G.N.; Dimopoulos, M.-A.; Mitrakou, A. Early and late endocrine complications of COVID-19. Endocr. Connect. 2021, 10, R229–R239.
  7. Soldevila, B.; Puig-Domingo, M.; Marazuela, M. Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated? Rev. Endocr. Metab. Disord. 2021, 23, 137–150.
  8. Moroti, R.; Badiu, C. Endocrine effects of COVID 19: Difficulties in the management of endocrine disorders from individual to societies. Acta Endocrinol. 2020, 16, 74–77.
  9. Clarke, S.A.; Abbara, A.; Dhillo, W.S. Impact of COVID-19 on the Endocrine System: A Mini-review. Endocrinology 2021, 163, bqab203.
  10. Damara, F.A.; Muchamad, G.R.; Ikhsani, R.; Hendro; Syafiyah, A.H.; Bashari, M.H. Thyroid disease and hypothyroidism are associated with poor COVID-19 outcomes: A systematic review, meta-analysis, and meta-regression. Diabetes Metab. Syndr. 2021, 15, 102312.
  11. Kim, S.-Y.; Yoo, D.-M.; Min, C.-Y.; Choi, H.-G. The Effects of Previous Thyroid Disease on the Susceptibility to, Morbidity of, and Mortality Due to COVID-19: A Nationwide Cohort Study in South Korea. J. Clin. Med. 2021, 10, 3522.
  12. Milani, N.; Najafpour, M.; Mohebbi, M. Case series: Rare cases of thyroid storm in COVID-19 patients. Clin. Case Rep. 2021, 9, e04772.
  13. Das, B.B.; Shakti, D.; Akam-Venkata, J.; Obi, O.; Weiland, M.D.; Moskowitz, W. SARS-CoV-2 infection induced thyroid storm and heart failure in an adolescent girl. Cardiol. Young 2021, 1–5.
  14. Poma, A.M.; Basolo, A.; Bonuccelli, D.; Proietti, A.; Macerola, E.; Ugolini, C.; Torregrossa, L.; Alì, G.; Giannini, R.; Vignali, P.; et al. Activation of Type I and Type II Interferon Signaling in SARS-CoV-2-Positive Thyroid Tissue of Patients Dying from COVID-19. Thyroid 2021, 31, 1766–1775.
  15. Dutta, A.; Jevalikar, G.; Sharma, R.; Farooqui, K.J.; Mahendru, S.; Dewan, A.; Bhudiraja, S.; Mithal, A. Low FT3 is an independent marker of disease severity in patients hospitalized for COVID-19. Endocr. Connect. 2021, 10, 1455–1462.
  16. Ahn, J.; Lee, M.K.; Lee, J.H.; Sohn, S.Y. Thyroid Hormone Profile and Its Prognostic Impact on the Coronavirus Disease 2019 in Korean Patients. Endocrinol. Metab. 2021, 36, 769–777.
  17. Varol, A.C.; Hatice, U.; Gorgun, S. COVID-19 and Hashimoto’s Disease. Rev. Assoc. Med. Bras. 2021, 67, 640.
  18. Sandru, F.; Carsote, M.; Albu, S.E.; Dumitrascu, M.C.; Valea, A. Vitiligo and chronic autoimmune thyroiditis. J. Med. Life 2021, 14, 127–130.
  19. Brănişteanu, D.E.; Dimitriu, A.; Vieriu, M.; Boda, D.; Stoleriu, G.; Molodoi, D.A.; Brănişteanu, D. Cutaneous manifestations associated with thyroid disease. Rev. Med. Chir. Soc. Med. Nat. Iasi 2014, 118, 953–958.
  20. Schomburg, L. Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease. Int. J. Mol. Sci. 2021, 22, 8532.
  21. Knack, R.S.; Hanada, T.; Knack, R.S.; Mayr, K. Hashimoto’s thyroiditis following SARS-CoV-2 infection. BMJ Case Rep. 2021, 14, e244909.
  22. Tee, L.; Harjanto, S.; Rosario, B. COVID-19 complicated by Hashimoto’s thyroiditis. Singap. Med. J. 2021, 62, 265.
  23. Yazdanpanah, N.; Rezaei, N. Autoimmune complications of COVID-19. J. Med. Virol. 2021, 94, 54–62.
  24. Szekanecz, Z.; Balog, A.; Constantin, T.; Czirják, L.; Géher, P.; Kovács, L.; Kumánovics, G.; Nagy, G.; Rákóczi, É.; Szamosi, S.; et al. COVID-19: Autoimmunity, multisystemic inflammation and autoimmune rheumatic patients. Expert Rev Mol Med. 2022, 24, e13.
  25. Qureshi, N.K.; Bansal, S.K. Autoimmune Thyroid Disease and Psoriasis Vulgaris after COVID-19 in a Male Teenager. Case Rep. Pediatr. 2021, 2021, 7584729.
  26. Malik, J.; Zaidi, S.M.J.; Waqar, A.U.; Khawaja, H.; Malik, A.; Ishaq, U.; Rana, A.S.; Awan, A.H. Association of hypothyroidism with acute COVID-19: A systematic review. Expert. Rev. Endocrinol. Metab. 2021, 16, 251–257.
  27. Dincer Yazan, C.; Ilgin, C.; Elbasan, O.; Apaydin, T.; Dashdamirova, S.; Yigit, T.; Sili, U.; Karahasan Yagci, A.; Sirikci, O.; Haklar, G.; et al. The Association of Thyroid Hormone Changes with Inflammatory Status and Prognosis in COVID-19. Int. J. Endocrinol. 2021, 2021, 2395212.
  28. Llamas, M.; Garo, M.L.; Giovanella, L. Low free-T3 serum levels and prognosis of COVID-19: Systematic review and meta-analysis. Clin. Chem. Lab. Med. (CCLM) 2021, 59, 1906–1913.
  29. Beltrão, F.E.L.; Beltrão, D.C.A.; Carvalhal, G.; Beltrão, M.F.E.L.; Brito, M.A.S.; Capistrano, M.K.H.R.; Bastos, I.H.D.A.; Hecht, F.; Daltro, C.H.D.C.; Bianco, A.C.; et al. Thyroid Hormone Levels During Hospital Admission Inform Disease Severity and Mortality in COVID-19 Patients. Thyroid 2021, 31, 1639–1649.
  30. Zarnywojtek, A.; Zgorzalewicz-Stachowiak, M.; Czarnywojtek, A.; Ochmańska, A.; Sawicka-Gutaj, N.; Matyjasek-Matuszek, B.; Wozniak, M.; Ruchała, M. Influence of SARS-CoV-2 infection on thyroid gland function: The current knowledge. Adv. Clin. Exp. Med. 2021, 30, 747–755.
  31. Dumitrascu, M.C.; Popescu, M.; Ghenea, A.E.; Carsote, M.; Petca, A.; Petca, R.C.; Sandru, F. COVID-19 and Basedow disease. Rom. J. Infect. Dis. 2021, 24, 185–189.
  32. Dumitrascu, M.C.; Petrova, E.; Rentea, D.E.; Zugravu, S.; Ghemigian, A.; Carsote, M.; Dumitrascu, A.; Mehedintu, C.; Sandru, F. COVID-19 pandemic and thyroid cancer. Rom. Med. J. 2021, 68, 445–449.
  33. Sandru, F.; Dumitrascu, M.C.; Rentea, D.E.; Petrova, E.; Draghici, A.; Ghemigian, A.; Dumitrascu, A.; Mehedintu, C.; Carsote, M. Pandemics and thyroid neoplasia. Rom. Med. J. 2021, 68, 533–535.
  34. Liu, H.; Zhan, L.; Guo, L.; Yu, X.; Li, L.; Feng, H.; Yang, D.; Xu, Z.; Tu, Y.; Chen, C.; et al. More Aggressive Cancer Behaviour in Thyroid Cancer Patients in the Post-COVID-19 Pandemic Era: A Retrospective Study. Int. J. Gen. Med. 2021, 14, 7197–7206.
  35. Sandru, F.; Dumitrascu, M.C.; Rentea, D.E.; Zugravu, S.; Petca, R.C.; Mehedintu, C.; Carsote, M. COVID-19 era and thyroid surgery. Rom. J. Med. Pract. 2021, 16, 484–488.
  36. Tunca, F.; Iscan, Y.; Sormaz, I.C.; Aksakal, N.; Senyurek, Y. Impact of the Coronavirus disease Pandemic on the Annual Thyroid, Parathyroid, And Adrenal Surgery Volume in A Tertiary Refferal Endocrine Surgery Center in 2020. Med. Bull. Sisli Etfal Hosp 2021, 55, 286–293.
  37. Trimboli, P.; Camponovo, C.; Scappaticcio, L.; Bellastella, G.; Piccardo, A.; Rotondi, M. Thyroid sequelae of COVID-19: A systematic review of reviews. Rev. Endocr. Metab. Disord. 2021, 22, 485–491.
  38. Vasile, C.; Udriștoiu, A.; Ghenea, A.; Popescu, M.; Gheonea, C.; Niculescu, C.; Ungureanu, A.; Udriștoiu, Ș.; Drocaş, A.; Gruionu, L.; et al. Intelligent Diagnosis of Thyroid Ultrasound Imaging Using an Ensemble of Deep Learning Methods. Medicina 2021, 57, 395.
  39. Rubinstein, T.J. Thyroid Eye Disease Following COVID-19 Vaccine in a Patient with a History Graves’ Disease: A Case Report. Ophthalmic Plast. Reconstr. Surg. 2021, 37, e221–e223.
  40. Zettinig, G.; Krebs, M. Two further cases of Graves’ disease following SARS-CoV-2 vaccination. J. Endocrinol. Investig. 2021, 45, 227–228.
  41. Murvelashvili, N.; Tessnow, A. A Case of Hypophysitis Following Immunization with the mRNA-1273 SARS-CoV-2 Vaccine. J. Investig. Med. High Impact Case Rep. 2021, 9, 23247096211043386.
  42. Vera-Lastra, O.; Navarro, A.O.; Domiguez, M.P.C.; Medina, G.; Valadez, T.I.S.; Jara, L.J. Two Cases of Graves’ Disease Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome Induced by Adjuvants. Thyroid 2021, 31, 1436–1439.
  43. Vojdani, A.; Vojdani, E.; Kharrazian, D. Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins with Tissue Antigens: Implications for Autoimmune Diseases. Front. Immunol. 2021, 11, 617089.
  44. Ku, C.R.; Jung, K.Y.; Ahn, C.H.; Moon, J.S.; Lee, J.H.; Kim, E.H.; Kwon, H.; Kim, H.K.; Suh, S.; Hong, S.; et al. COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society. Endocrinol. Metab. 2021, 36, 757–765.
  45. Puig-Domingo, M.; Marazuela, M.; Yildiz, B.O.; Giustina, A. COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology. Endocrine 2021, 72, 301–316.
  46. Oğuz, S.H.; Şendur, S.N.; Iremli, B.G.; Gürlek, A.; Erbas, T.; Ünlütürk, U. SARS-CoV-2 Vaccine-induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up. J. Clin. Endocrinol. Metab. 2022, dgac049.
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