Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination.

OBJECTIVE: COVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. METHODS: A population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. RESULTS: A total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). CONCLUSION: Based on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

The Effects of Corticosteroid and Nonsteroid Anti-Inflammatory Therapies on Permanent Hypothyroidism Occurring After the Subacute Thyroiditis.

OBJECTIVE: Subacute thyroiditis(SAT) is an acute inflammatory, self-limited, and destructive disease of the thyroid gland. Although it is a temporary disease, it has permanent consequences. We aim to investigate the influences of the treatment choice on permanent hypothyroidism occurring after SAT and whether there are predictive factors for the development of permanent hypothyroidism. METHODS: We retrospectively investigated 57 SAT patients admitted to our tertiary hospital between 2017 and 2019. After excluding 6 patients, demographic, clinical, laboratory, and imaging findings of 36 patients treated with NSAIDs and 15 patients treated with corticosteroids were compared. The median duration of follow-up was 4 (3.5-5.5) years. RESULTS: Permanent hypothyroidism occurred in 16 patients (31.4%) of 51 patients. It developed at a significantly higher rate in NSAID users (p=0.019). There was no significant difference in the occurrence of transient hypothyroidism and recurrence (p=0.472, p=0.082). The early maximum TSH values were strongly associated with permanent hypothyroidism. The Odds Ratio (OR) value was 2.59 (95% CI = 1.26 - 5.33, p=0.009), Nagelkerke R2 = 0.821. The early maximum TSH level had a predictive value, with an AUC of 0.966 for post-SAT permanent hypothyroidism (p<0.001). The cutoff values for the early maximum TSH were 9.07uIU/ml (81.3% sensitivity, 100% specificity), and 7.05 uIU/ml (87.5% sensitivity, 94.3% specificity). CONCLUSION: Corticosteroid therapy is significantly effective in preventing permanent hypothyroidism from developing after SAT. The early maximum TSH values are an indicator for the prediction of the development of permanent hypothyroidism.

Subacute thyroiditis presenting as simple acute headache was misdiagnosed as meningitis: case report and literature review.

BACKGROUND: The relationship between headache and thyrotoxicosis has been occasionally mentioned in case reports, but there are few related reports. Thus, the relationship cannot be determined. Few cases of subacute thyroiditis (SAT) presenting as simple headache have been reported. CASE PRESENTATION: This case report describes a middle-aged male patient who came to our hospital with acute headache for 10 days. He was initially misdiagnosed as meningitis due to headache, fever, and increased C-reactive protein. Routine antibacterial and antiviral therapy did not improve his symptoms. Blood test suggested thyrotoxicosis, and color ultrasound suggested SAT sonography. He was diagnosed with SAT. With the treatment of SAT, the headache was relieved after the thyrotoxicosis improved. CONCLUSION: This patient is the first detailed report of SAT presenting with simple headache, which is helpful for clinicians to differentiate and diagnose atypical SAT.

HLA typing of patients who developed subacute thyroiditis and Graves' disease after SARS-CoV-2 vaccination: a case report.

BACKGROUND: Cases of subacute thyroiditis (SAT) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. A human leukocyte antigen (HLA) allele, HLA-B*35, appears to be involved in the pathogenesis of SAT. CASE PRESENTATION: We conducted HLA typing of one patient with SAT and another with both SAT and Graves' disease (GD), which developed after SARS-CoV-2 vaccination. Patient 1, a 58-year-old Japanese man, was inoculated with a SARS-CoV-2 vaccine (BNT162b2; Pfizer, New York, NY, USA). He developed fever (38 °C), cervical pain, palpitations, and fatigue on day 10 after vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum C-reactive protein (CRP) and slightly increased serum antithyroid-stimulating antibody (TSAb) levels. Thyroid ultrasonography revealed the characteristic findings of SAT. Patient 2, a 36-year-old Japanese woman, was inoculated twice with a SARS-CoV-2 vaccine (mRNA-1273; Moderna, Cambridge, MA, USA). She developed fever (37.8 °C) and thyroid gland pain on day 3 after the second vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum CRP, TSAb, and antithyroid-stimulating hormone receptor antibody levels. Fever and thyroid gland pain persisted. Thyroid ultrasonography revealed the characteristic findings of SAT (i.e., slight swelling and a focal hypoechoic area with decreased blood flow). Prednisolone treatment was effective for SAT. However, thyrotoxicosis causing palpitations relapsed thereafter, for which thyroid scintigraphy with 99mtechnetium pertechnetate was conducted, and the patient was diagnosed with GD. Thiamazole treatment was then initiated, which led to improvement in symptoms. CONCLUSION: HLA typing revealed that both patients had the HLA-B*35:01, -C*04:01, and -DPB1*05:01 alleles. Only patient 2 had the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles. The HLA-B*35:01 and HLA-C*04:01 alleles appeared to be involved in the pathogenesis of SAT after SARS-CoV-2 vaccination, and the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles were speculated to be involved in the postvaccination pathogenesis of GD.

Ultrasound-Guided Capsular Thyroid Injection Therapy With Dexamethasone and Lidocaine Mixture for Subacute Thyroiditis: A Single-Center Study.

OBJECTIVES: Subacute thyroiditis (SAT) is a self-limiting, inflammatory thyroid disease possibly caused by viral infection. In recent years, the incidence of SAT is increasing, especially during the pandemic of the COVID-19. This study aimed to evaluate the efficacy, safety, and recovery time of capsular thyroid injection therapy under ultrasound guidance for SAT. METHODS: A total of 73 patients with SAT were divided into two groups. Patients in group A (n = 48) received an ultrasound-guided capsular injection consisting of dexamethasone (DEX) and lidocaine in the thyroid lesion area, while patients in group B (n = 25) received oral prednisolone (PSL). The two groups were compared for pain relief and treatment duration, the recovery time of thyroid function, recurrence rates, hypothyroidism incidence, and drug-related side effects. RESULTS: The follow-up time was 1 year. In group A, the duration of pain relief, treatment, and recovery time of thyroid function were significantly shorter than that in group B (P < .05), and no statistically significant differences in recurrence rate or incidence of hypothyroidism were observed (P > .05). Weight gain was significantly higher in group A at the end of treatment (P < .001). CONCLUSIONS: Compared with oral PSL treatment, ultrasound-guided local injection of DEX and lidocaine into the capsular thyroid is a safe and effective procedure that can significantly reduce the treatment time of SAT.

The association of subacute thyroiditis with viral diseases: a comprehensive review of literature

Introduction: Subacute thyroiditis (SAT), also known as de Quatrain's thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people's lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight. Objective: Regarding the importance of this issue, we decided to summarize our extensive searches from online databases, including PubMed, Google Scholar, Medline, Web of Science, and Scopus until February 2023, which we found effective in elucidating the association of subacute thyroiditis and viral diseases. Method: Different online databases were searched for narrative review articles, systemic review articles, and original articles, which were published until February 2023. Result: According to the included studies, we found that there is a correlation between SAT and several viruses such as Epstein-Barr virus, influenza virus, human immunodeficiency virus, cytomegalovirus, oral and cervical virus, hepatitis, dengue virus, and SARS-COV-2. The effect of each of the viral diseases mentioned in the SAT is given in the text. Conclusions: According to the results mentioned in the text, because SAT may be challenging for early diagnosis, due to the potential of classic symptoms as well as the interference of similar clinical symptoms between thyrotoxicosis and viral reactions, the correlation between SAT and viral diseases should be considered so that we can avoid misdiagnosis and lateness.

THE OCCURRENCE OF SUBACUTE THYROIDITIS AFTER THE AMELIORATION OF HYPERCORTISOLISM FOLLOWING TRANSSPHENOIDAL SURGERY IN CUSHING'S DISEASE.

Only a few subacute thyroiditis (SAT) cases secondary to hypocortisolemia developed after successfully treating Cushing's disease (CD) have been reported. In this report, we present an SAT case, which developed immediately after discontinuation of steroid treatment for hypocortisolemia after the successful treatment of CD. A 54-year-old female patient who had recently been diagnosed with type 2 diabetes mellitus was admitted to our center with complaints of proximal myopathy and obesity. Serum cortisol did not suppress adequately after the 1 mg dexamethasone suppression test. Pituitary MRI of the patient with increased basal plasma ACTH level revealed a 6 x 5 mm right-sided adenoma. After successful surgical treatment, the patient was given ten months of steroid therapy due to a suppressed corticotroph axis. Shortly after the steroid treatment was discontinued, the patient was admitted with neck pain, fever, and thyrotoxicosis. The patient was diagnosed with SAT, and methylprednisolone treatment was started again. The underlying pathophysiological mechanisms in SAT cases that develop after the treatment of CD can only be speculated. One possible mechanism could be that the glucocorticoid deficiency develops after effective treatment of hypercortisolism alters the immunological responses or generates self-reactive cells and prepares an appropriate environment for the thyrolytic process.

SUBACUTE THYROIDITIS FOLLOWING SARS-COV-2 VACCINATION: AN AUTOIMMUNE/INFLAMMATORY SYNDROME INDUCED BY ADJUVANTS (ASIA SYNDROME).

Context: Subacute thyroiditis, a manifestation of Autoimmune/inflammatory syndrome induced by adjuvants that may develop after vaccination. Objective: The aim of this study is to determine the importance of vaccination against COVID-19 in the etiology of subacute thyroiditis. Design: This case reports/series is an observational, descriptive research design. Subjects and Methods: Five of the thirty patients who applied to our clinic with subacute thyroiditis in the last 6 months had a history of inactivated and mRNA vaccines in the last four weeks, after exclusion of infection and comorbidities. We present three cases of mRNA-based vaccination and two cases of inactive SARS-CoV-2 vaccination that met ASIA criteria. Results: Our findings suggest that subacute thyroiditis may be a complication of vaccination against COVID-19. Conclusion: Vaccine administration may led to autoimmune manifestation induction as well as autoantibody production. Adjuvant-induced autoimmune/inflammatory syndrome, an abnormal autoimmune response as a result of exposure to an adjuvant such as vaccine, appears likely in our cases.

Management of thyroiditis in the context of Covid-19: cause-effect and beyond.

Background: The COVID-19 pandemic hit the world in late 2019, and by 2020, everyone was affected. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) belongs to the beta-coronavirus genre and uses the angiotensin-converting enzyme 2 (ACE2) receptor to penetrate cells. Thyroid cells are rich in such receptors. Therefore, this gland is frequently involved alongside other organs in the COVID-19 disease. Aim: To describe COVID-19 inflammation and, eventually, dysregulations of normal thyroid function in a case series of patients diagnosed in a tertiary endocrinology care centre. Patients and Methods: We described subacute thyroiditis cases related to COVID-19 infection or vaccination against SARS-CoV2 infection (clinical manifestations and evolution). We also reviewed the literature data regarding COVID-19 infection or vaccination implications in thyroid pathology. Results: The literature describes two types of thyroid involvement in SARS-CoV2 infection or vaccination: subacute thyroiditis (SAT) and non-thyroidal illness syndrome (NTIS). In our case series, 5 patients (3 males), aged 41-54 years, developed the classical clinical manifestation of SAT related to COVID-19 infection (3 patients, concomitantly to upper respiratory infection or a few weeks apart) or anti-SARS-CoV2 ARNm vaccination (1-2 weeks after the vaccine administration). Clinical, laboratory and imaging findings and the evolution (steroid anti-inflammatory treatment used in 4/5 cases) were unremarkable compared to other SAT etiologies. Conclusion: We found no differences between the "typical" viral and post-COVID-19 SAT regarding clinical presentation, severity, response to treatment, and thyroid function alteration. The only remarkable difference is the association of SAT with anti-SARS-CoV2 ARNm vaccination.

Cellular immunity in subacute thyroiditis: a new perspective through neopterin.

Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid gland. Although its etiology is not fully understood, it is believed to occur shortly after viral infections and is mostly associated with human leukocyte antigen (HLA)-B*35. Cellular immunity is prominent in SAT. Neopterin is produced by activated monocytes/macrophages and is a marker of cellular immunity. Its production is stimulated by interferon gamma (IFN-γ), provided mainly by activated helper T lymphocytes type 1 (Th1) in the adaptive immune system. Therefore, with these cells' activation, an increase in serum neopterin levels is expected. We aimed to evaluate neopterin levels in demonstrating cellular immunity in SAT and compared 15 SAT patients with 16 healthy controls. Since all SAT patients were in the active thyrotoxic phase, we found a significant difference in thyroid functions. Classical inflammatory markers, erythrocyte sedimentation rate, and C-reactive protein were markedly elevated in the patient group. Although we expected to find an increase considering that cellular immunity is at the forefront in the pathogenesis of SAT, we found serum neopterin levels significantly lower in the patient group than in the control group. There is an increase in CD8+ T cells in the thyroid tissue in SAT. The possible relationship with HLA-B*35- major histocompatibility complex class I in SAT, and the antigen presentation to CD8+ T cells may be the reason why we observed low serum neopterin levels in patients due to the cytokine imbalance. Neopterin provides unique and independent data from classical acute phase response indicators.

Subacute thyroiditis during early pregnancy: a case report and literature review.

BACKGROUND: Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy. CASE PRESENTATION: A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41. CONCLUSION: SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.

Subacute thyroiditis after SARS-Cov2 vaccination: A review of the cases being described and personal experience.

Objective. The present study evaluates the occurrence of subacute thyroiditis in temporal connection with SARS-Cov2 vaccinations described in the literature last year and confirmed by our clinical routine. Methods. Systematic literature search in Medline for studies reporting diagnosis of subacute thyroiditis in temporal connection with vaccinations against Covid 19. Results. The literature search yielded 24 relevant references out of which 22 were "case reports" and two "Letters to the Editor" and encompassed 37 patient cases, in total. They had received a SARS-Cov2 vaccination shortly before the diagnosis (median interval to vaccination six days). In none of these cases, infection of the upper respiratory tract had previously been identified as a classic trigger of the disease. Newly occurring hyperthyroidism and increased laboratory signs of inflammation were described in 78% and 74% of cases, respectively. Atypical clinical pictures (asymptomatic, euthyroid, no inflammation marks) have been observed in both the literature and our patients suspected of thyroid cancer referred to surgery. Conclusions. In times of pandemics and the resulting vaccination, new rapidly occurring sonographic changes in the thyroid gland should be revaluated after 2-3 weeks, or recommended to undergo a fine-needle biopsy, in order to avoid unnecessary surgical interventions.

Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence.

PURPOSE: The safety and efficacy of the several types of COVID-19 vaccines, including mRNA-based, viral vector-based, and inactivated vaccines, have been approved by WHO. The vaccines can confer protection against severe SARS-CoV-2 infection through induction of the anti-spike protein neutralizing antibodies. However, SARS-CoV-2 vaccines have been associated with very rare complications, such as thyroid disorders. This review was conducted to highlight main features of thyroid abnormalities following COVID-19 vaccination. METHODS: A comprehensive search within electronic databases was performed to collect reports of thyroid disorders after vaccination with COVID-19 vaccines. RESULTS: Among 83 reported cases including in this review, the most cases of thyroid abnormalities were observed after vaccination with mRNA-based vaccines (68.7%), followed by viral vector vaccines (15.7%) and 14.5% cases following inactivated vaccines. Subacute thyroiditis (SAT) was the most common COVID-19 vaccination-related thyroid disease, accounting for 60.2% of all cases, followed by Graves' disease (GD) with 25.3%. Moreover, some cases with focal painful thyroiditis (3.6%), silent thyroiditis (3.6%), concurrent GD and SAT (2.4%), thyroid eye disease (1.2%), overt hypothyroidism (1.2%), atypical subacute thyroiditis (1.2%), and painless thyroiditis with TPP (1.2%) were also reported. Overall, in 58.0% of SAT cases and in 61.9% of GD cases, the onset of the symptoms occurred following the first vaccine dose with a median of 10.0 days (ranged: 3-21 days) and 10.0 days (ranged: 1-60 days) after vaccination, respectively. Moreover, 40.0% of SAT patients and 38.1% of GD patients developed the symptoms after the second dose with a median of 10.5 days (ranged: 0.5-37 days) and 14.0 days (ranged: 2-35 days) after vaccination, respectively. CONCLUSION: Fortunately, almost all cases with COVID-19 vaccination-associated thyroid dysfunctions had a favorable outcome following therapy. The benefits of COVID-19 vaccinations in terms of terminating the pandemic and/or reducing mortality rates can exceed any risk of infrequent complications such as a transient thyroid malfunction.

SARS-CoV-2 vaccine-associated subacute thyroiditis.

PURPOSE: With coronavirus disease 2019 (COVID-19), subacute thyroiditis (SAT) cases are on the rise all over the world. COVID-19 vaccine-associated SAT cases have also been reported. In this article, we present our data on 11 vaccine-associated SAT cases. METHODS: Eleven patients were included in the study. Type of the vaccines patients received, time to the occurrence of SAT after vaccination, symptoms and laboratory findings, treatment given, and response to treatment were evaluated. RESULTS: The age of patients ranged from 26 to 73. Four of the patients were males, and seven were females. Symptoms of six patients were seen after BNT162b2 Pfizer/BioNTech COVID-19 mRNA vaccine®, and four of them after Coronavac inactivated SARS-CoV-2 vaccine®. In one patient, SAT developed after the first dose of BNT162b2, administered after two doses of Coronavac. The average time to the onset of symptoms was 22 days (15-37) after vaccination. CONCLUSIONS: The fact that both whole virus containing and genetic material containing vaccines cause SAT suggests that the trigger may be viral proteins rather than the whole viral particle. Although corticosteroids are commonly preferred in published vaccine-associated SAT cases, we preferred nonsteroidal anti-inflammatory therapy in our patients for sufficient vaccine antibody response. There is not enough information about whether patients who develop SAT can be revaccinated safely considering the ongoing pandemic. Further research is needed for a conclusion in the treatment and revaccination of these patients.

SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review.

PURPOSE: To perform a systematic review on published cases of subacute thyroiditis (SAT) secondary to SARS-CoV-2 vaccination, to highlight main features and increase the awareness of this condition. METHODS: Original reports of SAT developed after SARS-CoV-2 vaccination (mRNA, viral vector, or inactivated virus vaccines) were retrieved from a search of electronic databases. Individual patient data on demographics, medical history, type of vaccine, workup and therapies were collected. Wilcoxon rank-sum, Kruskal-Wallis and chi-squared tests were employed for comparisons. RESULTS: 30 articles including 48 reports were retrieved, 3 additional cases evaluated by the Authors were described and included for analysis. Of the 51 patients, 38 (74.5%) were women, median age was 39.5 years (IQR 34-47). Patients developed SAT after a median of 10 days (IQR 4-14) after the vaccine shot. Baseline thyroid exams revealed thyrotoxicosis in 88.2% of patients, decreasing at 31.6% at follow-up. Corticosteroids were used in 56.4% of treated patients. Patients undergoing non-mRNA vaccines were most frequently Asian (p = 0.019) and reported more frequently weight loss (p = 0.021). All patients with a previous diagnosis of thyroid disease belonged to the mRNA vaccine group. CONCLUSION: SARS-CoV-2 vaccine-associated SAT is a novel entity that should be acknowledged by physicians. Previous history of thyroid disease may predispose to develop SAT after mRNA vaccines, but further studies and larger cohorts are needed to verify this suggestion. SARS-CoV-2 vaccine-associated SAT is usually of mild/moderate severity and could be easily treated in most cases, thus it should not raise any concern regarding the need to be vaccinated.

Subacute thyroiditis during the COVID-19 pandemic: a prospective study.

PURPOSE: Subacute thyroiditis(SAT) is a destructive thyroiditis associated with viral infections. Several SAT cases associated with SARS-CoV-2 infection/vaccination were recently reported. We aimed to evaluate prospectively all cases applied to our tertiary center and their relationship with SARS-CoV-2 during 16 months of the pandemic. Cases during similar pre-pandemic period were recorded for numeric comparison. METHODS: Prospective study took place between March 2020 and July 2021. SAT was diagnosed by classical criteria. Swabs for SARS-CoV-2 and a wide respiratory viral panel (RV-PCR) were taken. Previous COVID-19 was assessed by SARS-CoV-2 IgM&IgG levels. Study group was divided into three as: CoV-SAT, patients who had or still have COVID-19, Vac-SAT, patients diagnosed within three months after SARS-CoV-2 vaccination and NonCoV-SAT, those not associated with COVID-19 or vaccination. RESULTS: Out of 64 patients, 18.8% (n = 12) was classified as CoV-SAT, 9.3% (n = 6) as Vac-SAT and 71.9% as (n = 46) NonCoV-SAT. SARS-CoV-2 RT-PCR tests on the diagnosis of SAT were negative in all, but two patients tested positive five days later, in second testing, performed upon clinical necessity. CoV-SAT and NonCoV-SAT groups were similar in terms of clinical, laboratory, and treatment characteristics. However, symptoms were milder and treatment was easier in Vac-SAT group (p = 0.006). CONCLUSIONS: Total number of SAT cases during the pandemic period was comparable to pre-pandemic period. However, a considerable rate of SARS-CoV-2 exposure in SAT patients was established. COVID-19 presented with SAT, as the first manifestation in three cases. Vaccine-related cases developed in a shorter time period, clinical presentation was milder, and only a few required corticosteroids.

SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?

INTRODUCTION: Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis. METHODS AND RESULTS: Specimen from fine-needle aspiration of a hypoechoic undefined area was analyzed for cytology and for SARS-CoV-2 detection. SARS-CoV-2 was retrieved by real-time polymerase chain reaction on the cytologic sample, which was then cultured on Vero E6 cells and demonstrated to be cytopathic. Whole-genome sequence was deposited. Histological exam diagnosed a rare case of primary thyroid sarcoma with diffuse and strong expression of mouse double minute 2 homolog (MDM2) oncoprotein. Ultrastructural examination confirmed, in several neoplastic cells, the presence of viral particles in cytoplasmic vacuoles. CONCLUSIONS: In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. Functional studies are needed to confirm this suggestive pathway.

Subacute thyroiditis and thyroid inflammatory nodule secondary to COVID-19: a primary care case report.

OBJECTIVE: To describe a case of subacute thyroiditis (SAT) secondary to COVID-19 in the primary health care (PHC). CASE DESCRIPTION: A 51-year-old woman was treated in a PHC facility for flu-like symptoms for 5 days and pain in the lower neck. Symptomatic drugs were prescribed, and the patient was tested for COVID-19. On reassessment, the patient presented a painful oedema on the thyroid gland, dysphagia, and improvement in flu-like symptoms. Nonsteroidal anti-inflammatories were prescribed, and thyroid function analysis and inflammatory markers were collected. Reassessment after 1 week showed positive polymerase chain reaction-rapid test for COVID-19, partial improvement of neck pain, alterations in thyroid hormone tests (suppressed thyroid stimulating hormone and slightly elevated T4), and elevated C-reactive protein. Thyroid gland ultrasonography (USG), anti-thyroglobulin, and anti-thyroid peroxidise (anti-TPO) antibodies were requested and prednisone was prescribed. Anti-thyroglobulin and anti-TPO antibodies were negative; thyroid USG showed a solid nodule in the left lobe (approximately 4 cm), classified as TIRADS-4. The patient was sent to the Endocrinology Service, and a thyroid fine needle aspiration was requested. USG prior to the examination evidenced a complete regression of the nodule, which was diagnosed as an inflammatory pseudo nodule. CONCLUSION: We presented the case of a patient who was treated in a PHC facility for rare findings of SAT secondary to mild COVID-19, concomitant with a thyroid nodule that had complete remission after approximately 3 months and was interpreted as an inflammatory pseudo nodule secondary to SAT. PHC professionals should be aware of this condition and conduct adequate follow-up of these patients.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.

Subacute thyroiditis with liver dysfunction following coronavirus disease 2019 (COVID-19) vaccination: report of two cases and a literature review.

Subacute thyroiditis is a transient inflammatory thyroid disease characterized by neck pain, fever, and typical symptoms associated with thyrotoxicosis. The incidence of subacute thyroiditis is higher in female than in male, and susceptibility is prominent in the 30-50-year age range. The variety of case reports on subacute thyroiditis associated with coronavirus disease 2019 (COVID-19) appears to be increasing, and subacute thyroiditis following COVID-19 vaccination has recently been reported. Herein, we report two cases of subacute thyroiditis that developed after receiving the COVID-19 mRNA vaccine, one of which exhibited remarkable liver dysfunction. The mechanism underlying the development of post-vaccination subacute thyroiditis remains unknown; however, one theory suggests that adjuvants contained in vaccines may play a role in triggering diverse autoimmune and inflammatory responses. Another possibility is the potential cross-reactivity between the coronavirus spike protein target produced by the mRNA vaccine and thyroid cell antigens. Common side effects of the COVID-19 vaccine include pain at the injection site, fever, fatigue, headache, muscle pain, chills, and nausea. These symptoms are usually resolved within a few days. Subacute thyroiditis may present symptoms similar to those of short-term vaccination side effects or exhibit non-specific symptoms, potentially leading to misdiagnosis or underdiagnosis. Therefore, clinicians should be aware of the possible development of subacute thyroiditis after COVID-19 vaccination.