Analysis of the functional state of the thyroid gland in children who underwent COVID-19

Introduction. Extrapulmonary manifestations of COVID-19 may include endocrine forms, including diseases of the pancreas, pituitary gland, gonads, and thyroid gland. The direct cytopathic effect of the virus lies in its ability to enter cells through the ACE-2 receptor located on the epithelial and endothelial cells of the endocrine glands, followed by expression, which creates the possibility of the development and progression of damage to the endocrine system, both inflammatory and autoimmune. Until now, it has not been fully studied what changes in the state of health await children and teenagers in the post-COVID period, the dynamics of changes in the functional state of the thyroid gland in children and adolescents living in the region of endemic goiter (Far Eastern Federal District) has not been assessed.
Aim. To assess of thyroid dysfunction in children who have had COVID-19.
Materials and methods. The clinic performed a clinical and laboratory examination of 41 children aged 5-17 years who had a new coronavirus infection. Hormones were determined using the test systems of “AlkorBio” (St. Petersburg) on a microplate reader Stat-Fax 2100 (USA): thyroid stimulating hormone (µU/mL), free thyroxine (pmol/L), thyroid peroxidase antibodies.
Results. It was determined that some children had clinical symptoms that may be associated with a possible involvement of the thyroid system: severe fatigue (61.0%), drowsiness (48.8%), memory loss (26.8%), depressed mood (14.6%), hair loss (14.6%), chilliness (4.9%), dry skin (4.9%). Ultrasound of the thyroid gland revealed a decrease in the volume of the gland in 46.3% and a diffuse enlargement of the thyroid gland in 9.8% of patients. In 33.3% of patients, the level of thyroid stimulating hormone in blood serum exceeded 3.4 mcU/mL, with a normal level of free thyroxine, which corresponds to subclinical hypothyroidism.
Conclusion. The obtained data suggest the possibility of subclinical dysfunction of the thyroid gland in children who have had a coronavirus infection. Based on the pathophysiology of SARS-CoV-2 infection, with the presence of clinical complaints, it is necessary to conduct a routine assessment of thyroid function in patients in the recovery and convalescence phase after COVID-19. Future prospective studies are needed to improve epidemiological and clinical knowledge and optimize the management of endocrine diseases in patients with COVID-19. 

1. World Health Organization. (2021). COVID-19 disease in children and adolescents: scientific brief, 29 September 2021. World Health Organization. Available at: https://apps.who.int/iris/handle/10665/345575

2. Dong Y., Mo X., Hu Y., Qi X., Jiang F., Jiang Z., Tong S. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics 2020; 145(6):e20200702. https://doi.org/10.1542/peds.2020-0702

3. Sudre C., Murray B., Varsavsky T., Graham M., Penfold R., Bowyer R., Pujol J.C., Klaser K., Antonelli M., Canas L., Molteni E., Modat M., Cardoso J., May A., Ganesh S., Davies R., Nguyen L., Drew D., Astley C., Joshi A., Merino J., Tsereteli N., Fall T., Gomez M., Duncan E., Menni C., Williams F.M.K., Franks P., Chan A., Wolf J., Ourselin S., Spector T., Steves C. Attributes and predictors of long COVID. Nat. Med. 2021; 27(4):626–631. https://doi.org/10.1038/s41591-021-01292-y

4. Poma A.M., Bonuccelli D., Giannini R., Macerola E., Vignali P., Ugolini C., Torregrossa L., Proietti A., Pistello M., Basolo A., Santini F., Toniolo A., Basolo F. COVID 19 autopsy cases: detection of virus in endocrine tissues. J. Endocrinol. Invest. 2022; 45(1): 209–214. https://doi.org/10.1007/s40618-021-01628-y

5. Lazareva M.A., Evseeva G.P., Suprun S.V., Rakitskaya E.V., Lebed’ko O.A. [Effect of COVID-19 on development and progression of endocrinopathies in children]. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2021; (82):116–128 (in Russian). https://doi.org/10.36604/1998-5029-2021-82-116-128

6. Mattar S., Koh S., Rama Chandran S., Cherng B. Subacute thyroiditis associated with COVID-19. BMJ Case Rep. 2020; 13(8):e237336. https://doi.org/10.1136/bcr-2020-237336

7. Scappaticcio L., Pitoia F., Esposito K., Piccardo A., Trimboli P. Impact of COVID-19 on the thyroid gland: an update. Rev. Endocr. Metab. Disord. 2021; 22:803–815. https://doi.org/10.1007/s11154-020-09615-z

8. Brancatella A., Ricci D., Viola N., Sgrò D., Santini F., Latrofa F. Subacute Thyroiditis After Sars-COV-2 Infection. J. Clin. Endocrinol. Metab. 2020; 105(7):2367–2370. https://doi.org/10.1210/clinem/dgaa276

9. Zou R., Wu C., Zhang S., Wang G., Zhang Q., Yu B., Wu Y., Dong H., Wu G., Wu S., Zhong Y. Euthyroid sick syndrome in patients with Covid-19. Front. Endocrinol. (Lausanne) 2020; 11:566439. https://doi.org/10.3389/fendo.2020.566439

10. Malik J., Malik A., Javaid M., Zahid T., Ishaq U., Shoaib M. Thyroid function analysis in COVID-19: A retrospective study from a single center. PLoS One 2021; 16(3):e0249421. https://doi.org/10.1371/journal.pone.0249421

11. Lania A., Sandri M.T., Cellini M., Mirani M., Lavezzi E., Mazziotti G. Thyrotoxicosis in patients with COVID-19: the THYRCOV study. Eur. J. Endocrinol. 2020; 183(4):381–387. https://doi.org/10.1530/EJE-20-0335

12. Alexopoulou O., Beguin C., De Nayer P., Maiter D. Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur. J. Endocrinol. 2004; 150(1):1–8. https://doi.org/10.1530/eje.0.1500001

13. Peterkova V.A., Bezlepkina O.B., Nagaeva E.V., Shiryaeva T.Y., Chikulaeva О.А., Vadina T.A., Shreder E.V., Taranushenko T.E., Petryaykina E.E., Malievskiy O.A., Kiyaev A.V., Kostrova I.B., Bashnina E.B., Mikhailova E.G., Girsh Y.V., Khramova E.B., Alimova I.L. Samsonova L. N., Bolotova N.V. [Clinical guidelines «Thyroiditis in children»]. Clinical and experimental thyroidology 2021; 17(3):4–21. https://doi.org/10.14341/ket12711

14. Troshina E.A., Melnichenko G.A., Senyushkina E.S., Mokrysheva N.G. [Adaptation of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal systems to a new infectious disease - COVID-19 in the context of the development of COVID-19 pneumonia and/or cytokine storm]. Clinical and experimental thyroidology 2020; 16(1):21–27 (in Russian). https://doi.org/10.14341/ket12461

15. Fadeev V.V., Morgunova T.B., Melnichenko G.A., Dedov I.I. [Draft of the clinical recommendations for diagnosis and treatment of hypothyroidism]. Clinical and experimental thyroidology 2021; 17(1):4–13 (in Russian). https://doi.org/10.14341/ket12702

16. RakitskayaE.V., Uchakina R.V., Kozlov V.K. [Functional activity of pituitary thyroid system with different variants of vegetative dysfunctions yndrome in teenegers]. Therapist 2013; (5):41–48 (in Russian).

17. Loschenko M.A., Uchakina R.V., Kozlov V.K. [The structure of the somatic pathology of adolescents with chronic kidney disease]. Yakut Medical Journal 2012; (4):7–9 (in Russian).

18. Nishihara E., Ohye H., Amino N., Takata K., Arishima T., Kudo T., Ito M., Kubota S., Fukata S., Miyauchi A. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern. Med. 2008; 48(8):725−729. https://doi.org/10.2169/internalmedicine.47.0740

19. Wei L., Sun S., Xu C.H., Zhang J., Xu Y., Zhu H., Peh S.C., Korteweg C., McNutt M.A., Gu J. Pathology of the thyroid in severe acute respiratory syndrome. Hum. Pathol. 2007; 38(1):95–102. https://doi.org/10.1016/j.humpath.2006.06.011

20. Caron P. Thyroid disorders and SARS‑CoV‑2 infection: From pathophysiological mechanism to patient management. Ann. Endocrinol. (Paris). 2020; 81(5):507–510. https://doi.org/10.1016/j.ando.2020.09.001

21. Allam M.M., El-Zawawy H.T., Ahmed S.M., Abdelhamid M.A. Thyroid disease and covid-19 infection: Case series. Clin. Case Rep. 2021; 9(6). Article number: e04225. https://doi.org/10.1002/ccr3.4225

22. Hariyanto T.I., Kurniawan A. Thyroid disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Diabetes Metab. Syndr. 2020; 14(5):1429–1430. https://doi.org/10.1016/j.dsx.2020.07.044