COVID-19-associated thyroid diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2]

Overview

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus named for the similarity of its symptoms to those caused by the severe acute respiratory syndrome. Coronavirus disease 2019 (COVID-19) has been considered a global pandemic since its first emergence in Wuhan, China. On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.COVID-19 has been found to affect several organs and body systems, including the endocrine system, with short-term and possible long-term consequences. Recent data shows that COVID-19 patients have experienced a range of thyroid diseases.

Historical Perspective

Classification

There is no established system for the classification of COVID-19-associated thyroid disorders.

Pathophysiology

The exact pathogenesis of COVID-19-associated thyroid diseases is not fully understood. However, the following hypotheses have been suggested for the development of thyroid dysfunction in COVID-19 patients. [3] [4] [5] [6] [7] [8]

Causes

Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called SARS-CoV-2 is the cause of COVID-19-associated thyroid diseases. To read more click here

Differentiating COVID-19-associated thyroid diseases from other Diseases

Epidemiology and Demographics

Risk Factors

There are no established risk factors for COVID-19-associated thyroid diseases.

Screening

There is insufficient evidence to recommend routine screening for COVID-19-associated thyroid diseases.

Natural History, Complications, and Prognosis

A number of observational studies have shown that COVID-19 infection may be linked to some thyroid diseases, including: [2] [9] [10] [11] [12] [13] [14] [15] [15] [16] [2]

  • Prognosis has generally been good in most cases of COVID-19 patients with hyperthyroidism/hypothyroidism.
    • In a patient with subacute thyroiditis, the thyroid function and inflammatory markers normalized in 40 days. [2]
  • In a study on 154 COVID-19 patients, Low fT3 (i.e., euthyroid sick syndrome) was associated with higher mortality and increased IL-6, suggesting poor prognosis in these patients. [17]

Diagnosis

Diagnostic Study of Choice

The diagnosis of COVID-19-associated thyroid diseases is made based on the thyroid function test (TFT), which measures serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH).

History and Symptoms

The symptoms of clinical hyperthyroidism in COVID-19 patients are similar to hyperthyroidism in the general population. The most common symptoms include:

The symptoms of clinical hypothyroidism in COVID-19 patients are similar to hypothyroidism in the general population. The most common symptoms include:

If accompanied by thyroiditis:

Physical Examination

The most common physical examination findings in patients with hyperthyroidism include: [18]

The most common physical examination findings in patients with hypothyroidism include:

Laboratory Findings

The laboratory findings in hyperthyroidism are:

  • Elevated levels of serum thyroxine (T4) and triiodothyronine (T3).
  • Undetectable serum TSH.
  • Total T4 and T3 measurements are influenced by multiple conditions affecting serum thyroxine-binding globulin (TBG). Thus, the measurement of free thyroid hormones; free T4 (FT4) and free T3 (fT3), is the gold standard for the diagnosis of Graves' disease.[19]
  • Antibodies against the TSH receptor (TRAbs) are pathognomonic for Graves' disease. They are detectable in the serum of about 98% of untreated patients.[20] Detection of TRAbs rules out other causes of thyrotoxicosis.[21]
  • Anti-thyroid peroxidase (TPO) and antithyroglobulin (Tg) antibodies are also detectable in many patients with Graves' disease, but it is not recommended to measure these antibodies for diagnosis in all patients.

The laboratory findings in hypothyroidism are:

The laboratory findings in euthyroid sick syndrome are:

Euthyroid sick syndrome T3

(80-180 ng/dl)

T4

(4.6-12 ug/dl)

FT4

(0.7-1.9 ng/dl)

TSH

(0.4 to 4.0mIU/L)

Reverse T3

(90 to 350pg/mL)

Mild euthyroid sick syndrome ↓ N N N ↑
Moderate euthyroid sick syndrome ↓ N N/↓ N/↓ ↑
Severe euthyroid sick syndrome ↓ ↓ N/↓ ↓ ↑
Recovery N/↓ N N N N/↑

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT scan

  • There are no CT scan findings associated with COVID-19-associated thyroid diseases.

MRI

  • There are no MRI findings associated with COVID-19-associated thyroid diseases.

Other Imaging Findings

Thyroid ultrasound

  • Thyroid ultrasound may help diagnose Graves's disease. Typically, the thyroid pattern in Graves' disease is hypoechoic. Thyroid ultrasound gives an accurate estimation of the thyroid size, which is important in planning the therapeutic management and allows the detection of thyroid nodules that may not be palpable on physical examination.

Color flow Doppler

  • Color flow Doppler (CFD) estimates the blood flow which, in hyperthyroid Graves' disease patients, is typically increased within the thyroid gland.
  • CFD can be useful in the differential diagnosis of Graves' disease and other causes of thyrotoxicosis characterized by a low blood flow to the thyroid, such as factitious thyrotoxicosis, painless and subacute thyroiditis. [24]

Other Diagnostic Studies

Radioactive iodine uptake

Thyroid Disease TSH receptor antibodies Thyroid Ultrasound Color flow Doppler Radioactive iodine uptake/Scan Other features
Graves' disease + Hypoechoic pattern ↑ ↑ Ophthalmopathy, dermopathy
Toxic nodular goiter - Multiple nodules - Hot nodules at thyroid scan -
Toxic adenoma - Single nodule - Hot nodule -
Subacute thyroiditis - Heterogeneous hypoechoic areas Reduced/absent flow ↓ Neck pain, fever, and elevated inflammatory markers
Painless thyroiditis - Hypoechoic pattern Reduced/absent flow ↓ Symptoms and signs of hypothyroidism
Hashimoto's thyroiditis - Diffusely enlarged thyroid gland with a heterogeneous echotexture Normal early stages: may show increased uptake, late stages: single or multiple areas of reduced uptake (cold spots) -
  • To view other diagnostic studies for COVID-19, click here.

Treatment

Medical Therapy

  • Treatment of COVID-19-associated thyroid diseases generally depends on the presentation of thyroid disease.
  • No specific treatment has been reported for COVID-19-associated thyroid disease.

Surgery

Surgery is not a treatment option for patients with COVID-19-associated thyroid diseases.

Primary Prevention

There are no established measures for the primary prevention of COVID-19-associated thyroid diseases.

Secondary Prevention

There are no established measures for the secondary prevention of COVID-19-associated thyroid diseases.

References

  1. ↑ "WHO Western Pacific | World Health Organization".
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F (2020). "Subacute Thyroiditis After Sars-COV-2 Infection". J Clin Endocrinol Metab. 105 (7). doi:10.1210/clinem/dgaa276. PMC 7314004 Check |pmc= value (help). PMID 32436948 Check |pmid= value (help).
  3. ↑ Lisco G, De Tullio A, Jirillo E, Giagulli VA, De Pergola G, Guastamacchia E; et al. (2021). "Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects". J Endocrinol Invest. 44 (9): 1801–1814. doi:10.1007/s40618-021-01554-z. PMC 7992516 Check |pmc= value (help). PMID 33765288 Check |pmid= value (help).
  4. ↑ Lazartigues E, Qadir MMF, Mauvais-Jarvis F (2020). "Endocrine Significance of SARS-CoV-2's Reliance on ACE2". Endocrinology. 161 (9). doi:10.1210/endocr/bqaa108. PMC 7454499 Check |pmc= value (help). PMID 32652001 Check |pmid= value (help).
  5. ↑ Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P (2021). "Impact of COVID-19 on the thyroid gland: an update". Rev Endocr Metab Disord. 22 (4): 803–815. doi:10.1007/s11154-020-09615-z. PMC 7688298 Check |pmc= value (help). PMID 33241508 Check |pmid= value (help).
  6. ↑ Fliers E, Bianco AC, Langouche L, Boelen A (2015). "Thyroid function in critically ill patients". Lancet Diabetes Endocrinol. 3 (10): 816–25. doi:10.1016/S2213-8587(15)00225-9. PMC 4979220. PMID 26071885.
  7. ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID doi:10.1210/clinem/dgaa813 Check |pmid= value (help).
  8. ↑ Leow MK, Kwek DS, Ng AW, Ong KC, Kaw GJ, Lee LS (2005). "Hypocortisolism in survivors of severe acute respiratory syndrome (SARS)". Clin Endocrinol (Oxf). 63 (2): 197–202. doi:10.1111/j.1365-2265.2005.02325.x. PMC 7188349 Check |pmc= value (help). PMID 16060914.
  9. ↑ 9.0 9.1 9.2 Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ (2020). "Subacute thyroiditis associated with COVID-19". BMJ Case Rep. 13 (8). doi:10.1136/bcr-2020-237336. PMC 7449350 Check |pmc= value (help). PMID 32843467 Check |pmid= value (help).
  10. ↑ 10.0 10.1 10.2 Asfuroglu Kalkan E, Ates I (2020). "A case of subacute thyroiditis associated with Covid-19 infection". J Endocrinol Invest. 43 (8): 1173–1174. doi:10.1007/s40618-020-01316-3. PMC 7273820 Check |pmc= value (help). PMID 32504458 Check |pmid= value (help).
  11. ↑ 11.0 11.1 11.2 Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F; et al. (2020). "Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series". J Clin Endocrinol Metab. 105 (10). doi:10.1210/clinem/dgaa537. PMC 7454668 Check |pmc= value (help). PMID 32780854 Check |pmid= value (help).
  12. ↑ 12.0 12.1 12.2 Chakraborty U, Ghosh S, Chandra A, Ray AK (2020). "Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity". BMJ Case Rep. 13 (12). doi:10.1136/bcr-2020-239953. PMC 7750881 Check |pmc= value (help). PMID 33370933 Check |pmid= value (help).
  13. ↑ 13.0 13.1 13.2 Campos-Barrera E, Alvarez-Cisneros T, Davalos-Fuentes M (2020). "Subacute Thyroiditis Associated with COVID-19". Case Rep Endocrinol. 2020: 8891539. doi:10.1155/2020/8891539. PMC 7522602 Check |pmc= value (help). PMID 33005461 Check |pmid= value (help).
  14. ↑ 14.0 14.1 14.2 Tee LY, Harjanto S, Rosario BH (2021). "COVID-19 complicated by Hashimoto's thyroiditis". Singapore Med J. 62 (5): 265. doi:10.11622/smedj.2020106. PMC 8801861 Check |pmc= value (help). PMID 32668831 Check |pmid= value (help).
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 Dixit NM, Truong KP, Rabadia SV, Li D, Srivastava PK, Mosaferi T; et al. (2020). "Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19". J Endocr Soc. 4 (10): bvaa130. doi:10.1210/jendso/bvaa130. PMC 7499619 Check |pmc= value (help). PMID 32984743 Check |pmid= value (help).
  16. ↑ 16.0 16.1 16.2 Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A; et al. (2020). "SARS-CoV-2-related atypical thyroiditis". Lancet Diabetes Endocrinol. 8 (9): 739–741. doi:10.1016/S2213-8587(20)30266-7. PMC 7392564 Check |pmc= value (help). PMID 32738929 Check |pmid= value (help).
  17. ↑ Dabas A, Singh H, Goswami B, Kumar K, Dubey A, Jhamb U; et al. (2021). "Thyroid Dysfunction in COVID-19". Indian J Endocrinol Metab. 25 (3): 198–201. doi:10.4103/ijem.ijem_195_21. PMC 8547402 Check |pmc= value (help). PMID 34760673 Check |pmid= value (help).
  18. ↑ Terry J. Smith & Laszlo Hegedus (2016). "Graves' Disease". The New England journal of medicine. 375 (16): 1552–1565. doi:10.1056/NEJMra1510030. PMID 27797318. Unknown parameter |month= ignored (help)
  19. ↑ Dufour DR (2007). "Laboratory tests of thyroid function: uses and limitations". Endocrinol. Metab. Clin. North Am. 36 (3): 579–94, v. doi:10.1016/j.ecl.2007.04.003. PMID 17673120.
  20. ↑ Zöphel K, Roggenbuck D, Schott M (2010). "Clinical review about TRAb assay's history". Autoimmun Rev. 9 (10): 695–700. doi:10.1016/j.autrev.2010.05.021. PMID 20594972.
  21. ↑ Barbesino G, Tomer Y (2013). "Clinical review: Clinical utility of TSH receptor antibodies". J. Clin. Endocrinol. Metab. 98 (6): 2247–55. doi:10.1210/jc.2012-4309. PMC 3667257. PMID 23539719.
  22. ↑ Simmons, PJ (1998). "Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a role of interleukin-1beta and interleukin-6". Endocrinology. 139 (7): 3158–3186. doi:10.1210/en.139.7.3148. PMID 9645688.
  23. ↑ Giannini, AJ (1986). The Biological Foundations of Clinical Psychiatry. New Hyde Park, NY: Medical Examination Publishing Company. pp. 193–198. ISBN 0-87488-449-7.
  24. ↑ Kahaly GJ, Bartalena L, Hegedüs L (2011). "The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: a European perspective". Thyroid. 21 (6): 585–91. doi:10.1089/thy.2011.2106.ed3. PMID 21663420.
  25. ↑ Terry J. Smith & Laszlo Hegedus (2016). "Graves' Disease". The New England journal of medicine. 375 (16): 1552–1565. doi:10.1056/NEJMra1510030. PMID 27797318. Unknown parameter |month= ignored (help)
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