key: cord-0738257-0qdac14r
authors: Anwar, Sumadi Lukman; Wahyono, Artanto; Dwianingsih, Ery Kus; Avanti, Widya Surya
title: Thyrotoxicosis occurrence in SARS-CoV-2 infection: A case report
date: 2022-04-29
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2022.103700
sha: 85647d7d9b3fa05e984b5e74909fdbf3b88157fc
doc_id: 738257
cord_uid: 0qdac14r

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) is predominantly manifested as respiratory distress. There are growing reports of extrapulmonary clinical manifestations of COVID-19 in addition to the respiratory symptoms. COVID-19 has been associated with the thyroid function through Angiotensin-converting enzyme 2 (ACE2), the central mechanism through Thyroid Stimulating Hormone (TSH), and direct replication of the virus. CASE PRESENTATION: A 26-year-old woman presented with complaints of palpitation and abdominal pain for three days. Because the symptoms were worsening, she was brought to the emergency room. Her temperature was 37.9 °C without any symptoms of cough, coryza, sneezing, nor headache. Physical examination revealed tremor, tachycardia with 162 beats per minute (bpm), excessive sweating, hyperreflexia of patellar reflex, and no prominent lump in the neck. Electrocardiography (ECG) showed supraventricular tachycardic rhythm (SVT) and 150 J cardioversions were performed. The ECG converted to sinus rhythm, regular, with 120 bpm. Thyroid function tests showed an elevated fT4 level (>7.77 ng/dL) and low TSH level (<0.005 μIU/mL). Chest X-ray showed slight cardiomegaly without prominent abnormality in the lungs that was confirmed with thoracic computerized tomography. The result of the rapid antigen test for COVID-19 was positive and confirmed with polymerase chain reaction testing. She was then treated in the intensive isolation room with remdesivir, anti-hyperthyroid, and supportive therapy. As her condition improved, she was shifted to a non-intensive isolation room and was discharged from the hospital at day 7. DISCUSSION: COVID-19 could present as a thyroid crisis as the initial clinical manifestation. Clinicians should be aware that presentation of thyroid dysfunction in a patient without previous endocrine disease could be due to COVID-19 infection. Early recognition, anti-hyperthyroid therapy, and following isolation procedures for COVID-19 are required in the emergency condition.

The Coronavirus Disease 2019 caused by the recently identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is primarily associated with respiratory symptoms 1 Thyrotoxicosis is a condition associated with elevated thyroid hormone levels in the circulation 3 . The clinical manifestations vary from asymptomatic to a potentially fatal condition 3, 4 .

Misdiagnosis and inadequate treatment of thyrotoxicosis might lead to dangerous complications, including atrial fibrillation, muscle weakness, osteoporosis, delirium, altered mental status, cardiovascular failure, and death 3, 4 . A subset of severe COVID-19 patients with cytokine storm has been associated with overwhelming inflammatory responses in the thyroid gland. Interleukin-6 (IL-6) is reported to destroy both the structure and function of the thyroid gland, although the exact mechanisms are not yet fully explained 5 . All patients with thyroid dysfunction after COVID-19

infection have been associated with pneumonia either moderate to severe 6 .

Hyperthyroidism and hypothyroidism have been reported as sequalae of COVID-19 infection 2,5,6 . However, there is a paucity of data on the clinical manifestations and severity in critically ill patients with COVID-19, and a lack of guidelines in the clinical management of thyroid crisis due to COVID-19 infection 2,7 . In young patients, COVID-19 clinical manifestations are usually presented with mild and moderate respiratory symptoms 1 . We presented a case of thyrotoxicosis of a patient with COVID-19 infection. We reported our case following the SCARE guidelines 8 . rhythm, regular, with 120 bpm. Thyroid function tests were then performed that revealed a state of thyroid crisis with high fT4 (>7.77 ng/dL), and low TSH (<0.005 µIU/mL), while no TSH-stimulating antibody testing was available in our center. Complete blood counts showed white blood cells 8,400/mm 3 , hemoglobin 11.5 g/dL, normal limits of coagulation test results, normal liver and renal function test results, and mild hypomagnesemia (1.56 mg/dL). Ultrasonography of the neck showed a non-enlarged thyroid gland with slight edema, a marked increase of vascularization, and no additional lesion was observed. Chest X-ray showed slight cardiomegaly without prominent abnormality in the lungs and it was confirmed with computerized tomography. Results from the rapid antigen test for COVID-19 was positive and confirmed with polymerase chain reaction (PCR) tests.

She was then transferred to the intensive isolation room and treated with remdesivir 200 mg iv once/day on the first day, followed with 100 mg iv once/day on day 2-5. She also received thyrozol 20mg once a day, propranolol 40mg three times a day, Vitamin D 5000 units once a day orally and intravenously 1000 mg vitamin C once a day. As her condition was improved, she was shifted to nonintensive isolated room and was discharged from the hospital at day 7. She was then shifted to the non-intensive isolation room and was discharged on the day 7. She was advised to take orally thyrozol and propranolol until the next evaluation at the outpatient clinic. In the follow-up 1 week later, symptoms of hyperthyroidism were resolved and the thyroid function test results improved (normal free T4). There was complete symptom resolution in the following month with maintenance of oral thyrozol 20 mg once a day and propranolol 20 mg three times a day.

Here, we presented a case of a thyroid storm in association with COVID-19 infection. The patient was not directly suspected for COVID-19 infection until the positive swab test was reported.

The association of thyroid dysfunction and COVID-19 infection has not been fully explained 2,5 .

ACE2 and TMPRSS2 are two transmembrane proteins which are fundamentally required in the internalization of SARS-CoV-2 into host cells, thus contributing to the pathogenesis of COVID-19 9 . These two proteins are expressed in numerous tissues including in the thyroid gland. The highest levels of ACE2 expression and activity were found in the small intestines, kidneys, heart, salivary glands, testicles, and thyroid, whereas lower levels were observed in the brain, skin, pituitary gland, and skeletal muscles 2, 10 . Follicular cells lining the colloid lumen express ACE2 protein that could mediate SARS-CoV-2 internalization to further induce inflammation in the thyroid gland 2 . The virus internalization is mediated by integrin αvβ3 protein through its ability to bind to the Arg-Gly-Asp (RGD) and Lys-Gly-Asp (KGD) structures available both in the ACE2 protein and SARS-CoV-2 J o u r n a l P r e -p r o o f spike protein 2, 11 . It is suggested that thyroid hormones also bind to the integrins in the cell membranes causing activation of cytokine genes that subsequently contribute in the thyrotoxicosis 11,12 .

CD8 + T cells and persist during the resolution phase of COVID-19 infection 13 . In response to the infection, several cytokines and chemokines, including Interleukin (IL)-1β, Tumor Necrosis Factor (TNF) alpha, interferon (IFN) gamma, and monocyte chemoattractant protein 1 will be activated 14, 15 .

In patients with severe symptoms, the abundant systemic inflammation can cause thyroid dysfunction 14, 15 . In addition, SARS-CoV-2 is able to divert immunotolerance causing primary thyrotoxicosis, exacerbating earlier thyroid disorder, initiating an idiopathic orf immune-mediated thyroiditis, or inducing a recurrence 16, 17 . 

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