The co-occurrence of SAT, hypophysitis, and Schnitzler syndrome after COVID-19 vaccination: the first described case.

Subacute thyroiditis (also known as granulomatous thyroiditis, giant cell thyroiditis, de Quervain's disease, or SAT) is an inflammatory disease of the thyroid gland, usually spontaneously remitting, that lasts for weeks to months. However, recurrent forms sometimes occur which may have a genetic basis. In our paper, we have focused on the pathogenetics, symptoms, and treatment of SAT. We have described the 17-month disease course of a woman with persistent recurrent steroid-resistant SAT. SAT was well established and the patient's symptoms were not only recurrent neck pain with fever, but also recurrent chronic urticaria, which are symptoms that fulfil the criteria for the diagnosis of Schnitzler syndrome. Schnitzler syndrome occurred after vaccination with COVID-19 in the mechanism of ASIA syndrome. In our patient, Schnitzler syndrome involved the thyroid gland, causing persistent subacute thyroiditis, and the pituitary gland, causing transient swelling of the pituitary, which, to our knowledge, is the first reported case in the literature. Also unprecedented, as far as we know, is the fact that we performed thyroidectomy in the above patient, which reduced systemic inflammation and caused SAT to resolve, although only the inclusion of anakinra treatment resulted in resolution of the underlying condition.

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.

Subacute thyroiditis following COVID-19 vaccination: Case presentation.

Background: Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19.Purpose: The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine.Research design and study sample: Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal.Data collection and/or Analysis: Data collected during the disease are integral to the medical record.Results: Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.Conclusions: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

Subacute thyroiditis following COVID-19: A systematic review.

Background: Subacute thyroiditis (SAT) is a self-limiting thyroid inflammatory disease occurring specifically after upper respiratory tract infections. Since COVID-19 is a respiratory disease leading to multi-organ involvements, we aimed to systematically review the literature regarding SAT secondary to COVID-19. Methods: We searched Scopus, PubMed/MEDLINE, Cochrane, Web of Science, ProQuest, and LitCovid databases using the terms "subacute thyroiditis" and "COVID-19" and their synonyms from inception to November 3, 2022. We included the original articles of the patients with SAT secondary to COVID-19. Studies reporting SAT secondary to COVID-19 vaccination or SAT symptoms' manifestation before the COVID-19 infection were not included. Results: Totally, 820 articles were retained. Having removed the duplicates, 250 articles remained, out of which 43 articles (40 case reports and three case series) with a total of 100 patients, were eventually selected. The patients aged 18-85 years (Mean: 42.70, SD: 11.85) and 68 (68%) were women. The time from the onset of COVID-19 to the onset of SAT symptoms varied from zero to 168 days (Mean: 28.31, SD: 36.92). The most common symptoms of SAT were neck pain in 69 patients (69%), fever in 54 (54%), fatigue and weakness in 34 (34%), and persistent palpitations in 31 (31%). The most common ultrasonographic findings were hypoechoic regions in 73 (79%), enlarged thyroid in 46 (50%), and changes in thyroid vascularity in 14 (15%). Thirty-one patients (31%) were hospitalized, and 68 (68%) were treated as outpatients. Corticosteroids were the preferred treatment in both the inpatient and outpatient settings (25 inpatients (81%) and 44 outpatients (65%)). Other preferred treatments were nonsteroidal anti-inflammatory drugs (nine inpatients (29%) and 17 outpatients (25%)) and beta-blockers (four inpatients (13%) and seven outpatients (10%)). After a mean duration of 61.59 days (SD: 67.07), 21 patients (23%) developed hypothyroidism and thus, levothyroxine-based treatment was used in six of these patients and the rest of these patients did not receive levothyroxine. Conclusion: SAT secondary to COVID-19 seems to manifest almost similarly to the conventional SAT. However, except for the case reports and case series, lack of studies has limited the quality of the data at hand.

A Case Report of Concurrent Graves' Disease and Subacute Thyroiditis Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome (ASIA).

BACKGROUND: The response against adjuvants in vaccines is presented as autoimmune/inflammatory syndrome (ASIA). In this case report, we presented both SAT and Graves' disease in a patient as ASIA following the BNT162b2 mRNA COVID-19 vaccination. CASE PRESENTATION: A 31-year-old woman was admitted to the endocrinology outpatient clinic with the complaint of neck pain following the second dose of the BNT162B2 SARS-CoV-2 (Pfizer/BioNTech) vaccine. On physical examination, her thyroid gland was tender on palpation. Her thyroid function tests were compatible with hyperthyroidism, and inflammatory markers were high. In the thyroid ultrasonography (US) examination, we observed bilateral diffuse hypoechoic areas in the thyroid gland and increased vascularity in some parts of the thyroid. Anti-thyroid stimulating hormone receptor antibodies (TRAB) were positive. Overall, we considered concurrent subacute thyroiditis (SAT) and Graves' disease. CONCLUSION: The present study may be the first report to evaluate SAT and Graves' disease as ASIA following mRNA COVID-19 vaccination. Clinicians should be aware of possible vaccine-related complications.

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.

Autoimmune and inflammatory thyroid diseases following vaccination with SARS-CoV-2 vaccines: from etiopathogenesis to clinical management.

Since the Covid-19 pandemic emerged in 2019, several adenoviral-vectored, mRNA-based and inactivated whole-virus vaccines have been developed. A massive vaccination campaign has been undertaken around the world, and an increasing number of SARS-CoV-2 vaccine-induced thyroid diseases have been described in the literature. Subacute thyroiditis has been reported in 52 patients, mean age 45.5 ± 1.8 years, mainly in women (n = 39). Graves' disease is more frequent in women (n = 22) than in men (n = 10), mean age 46.2 ± 2.6 years, reported as new onset, recurrent or exacerbation of well-controlled hyperthyroidism. The mean time to symptoms onset is 9.0 ± 0.8 days in subacute thyroiditis, and 15.1 ± 2.6 days in Graves' patients. Rare patients (n = 6) present silent or painless autoimmune thyroiditis. Thyroid function and autoimmune tests, inflammatory markers, thyroid echography with colour flow Doppler, radio-activity uptake on thyroid scan, medical treatment and follow-up are described and compared in patients with SARS-CoV-2 vaccine-induced thyroid diseases. The underlying pathogenic mechanisms of vaccine-induced thyroid diseases, molecular mimicry (various SARS-CoV-2 proteins sharing a genetic homology with a large heptapeptide human protein) or autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are discussed in the context of predisposition or genetic susceptibility. The benefits of SARS-CoV-2 vaccination far outweigh the potential vaccine-induced adverse effects, but clinicians should be aware of possible autoimmune and inflammatory thyroid diseases, and can advise patients to seek medical assistance when experiencing anterior neck pain, fever or palpitations following SARS-CoV-2 vaccines. Further studies are warranted to investigate the etiopathogenesis and to clarify the factors which predispose patients to SARS-CoV-2 vaccine-induced thyroid diseases.

Subacute thyroiditis and COVID-19 vaccines: a case/non-case study.

PURPOSE: Some case reports have suggested a possible association between COVID-19 vaccines and subacute thyroiditis (SAT), however, to our knowledge, no study has analyzed this possible relationship. This study aimed to analyze whether a disproportionate number of cases of SAT were reported in the EudraVigilance database for four COVID-19 vaccines (BNT162b2, mRNA-1273 ChAdOx1-S or Ad26.COV2.S). METHODS: A case/non-case study was conducted to assess the association between SAT and COVID-19 vaccines, calculating the reporting odds ratios (RORs) up to December 2, 2021. Cases were selected using the preferred term 'subacute thyroiditis'. First, cases involving COVID-19 vaccines were compared with those involving all other drugs. Secondly, the RORs for COVID-19 vaccines compared with other viral vaccines (overall and influenza vaccines only) were obtained. RESULTS: Until December 2, 2021, of 1,221,582 spontaneous cases of adverse reactions with the four vaccines, we found 162 SAT cases: BNT162b2 (n = 103), mRNA-1273 (n = 27), ChAdOx1-S (n = 31) and Ad26.COV2.S (n = 1). SAT cases were found to be reported more frequently in association with BNT162b2, mRNA-1273, and ChAdOx1-S vaccines than with other drugs. Moreover, we found a signal of disproportionate reporting for SAT with BNT162b2 and mRNA-1273 vaccines comparing with other viral vaccines (BNT162b2 ROR 3.58, 95% CI 1.92-6.66; mRNA-1273 ROR 3.44, 95% CI 1.71-6.94). However, this association was absent when these COVID-19 vaccines were compared with influenza vaccines. CONCLUSIONS: In EudraVigilance, SAT is relatively more frequently reported in association with mRNA COVID-19 vaccines than with other viral vaccines. Well designed observational studies are needed to confirm these results.

Evaluation of the diagnostic features and clinical course of COVID-19 vaccine-associated subacute thyroiditis.

OBJECTIVE: This study aimed to identify cases of coronavirus disease 2019 (COVID-19) vaccine-associated subacute thyroiditis (SAT) during the active vaccination period of the pandemic, analyze the characteristics of these cases, and compare them with cases of non-vaccine associated SAT diagnosed in the same period. METHODS: A total of 55 patients diagnosed with SAT in our outpatient clinic between February and October, 2021, were included in this retrospective single-center study. RESULTS: Of the study population, 16 (29.1%) were diagnosed with COVID-19 vaccine-associated SAT (10 with CoronaVac® and six with Pfizer-BioNTech® vaccine), with a median time to onset of symptoms after vaccination of 6.5 (range, 2-20) days. There was no statistically significant difference between the vaccine-associated (VA) and non-vaccine associated (NVA) groups in terms of age, gender, time to diagnosis, thyroid volumes, thyroid function tests, and acute phase reactants. Seven (43.8%) and 25 (64.1%) patients were treated with methylprednisolone in the VA group and NVA group, respectively (p = 0.16). Follow-up data of 45 patients (16/16 for VA and 29/39 for NVA) were available. The mean follow-up of these patients was 47.4 ± 19.4 days, and the follow-up periods of the VA group and NVA group were comparable (p = 0.24). There was no difference between the two groups in terms of the frequency of euthyroidism at the follow-up visit (12/16 vs.14/29, p = 0.08). CONCLUSION: With the increase in COVID-19 vaccination rates during the current pandemic, VA SAT cases are seen more frequently. The present study demonstrated that these cases have similar diagnostic features and clinical course to that of classic forms of SAT. In addition, most patients with VA SAT had a mild clinical course that improved with non-steroidal anti-inflammatory drugs.

Differences in Clinical Aspects Between Subacute Thyroiditis Associated with COVID-19 Vaccines and Classical Subacute Thyroiditis.

Subacute thyroiditis (SAT) developed after SARS-CoV-2 vaccines has been less studied. We aimed to compare classical SAT and SAT developed after SARS-CoV-2 vaccines in the context of clinical aspects. Adults with SAT detected in 90 days of COVID-19 vaccination (CoronaVac or Pfizer/BioNTech) were grouped as Vac-SAT. Those with a history of SARS-CoV-2 or upper respiratory tract infection in 6 months before the vaccination, or vaccination with another antiviral vaccine after COVID-19 vaccination were excluded. Those with SAT detected before COVID-19 pandemic were grouped as Classical-SAT. Of total (n=85), female/male (54/31) ratio and age [43 (23-65)] were similar in Vac-SAT (n=23) and Classical-SAT (n=62). Duration between vaccine and SAT was 45 (7-90) days, and similar in CoronaVac-SAT (n=5) and BioNTech-SAT (n=18). SAT-duration was 28 (10-150) days, and higher in Vac-SAT than in Classical-SAT (p=0.023). SAT was developed after the 1st dose vaccine in minority in CoronaVac-SAT (n=2) and BioNTech-SAT (n=3) (p=0.263). Previous LT4 use, and TSH elevation after resolution were more frequent in Vac-SAT than in Classical-SAT (p=0.027 and p=0.041). We included a considerable number of patients with SAT occurred after COVID-19 vaccines. We cannot provide clear evidence regarding the association of COVID-19 vaccines with SAT. SAT associated with CoronaVac or BioNTech seems unlikely to be occurred after the 1st dose, and to have a longer duration, more likely to be associated with previous LT4 use and lead TSH elevation after resolution than Classical-SAT. TSH should be followed-up after the resolution of SAT detected after COVID-19 vaccination.

Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler: A case report.

RATIONALE: The occurrence of subacute thyroiditis (SAT) after vaccines or after hyaluronic acid skin fillers is very rare and might be related to genetic susceptibility. We suggest that the co-administration of both products could potentially increase the possibility of development of SAT. PATIENT CONCERNS: A 58-year-old Caucasian healthy female initially presented with chills, myalgia, dysphagia, sore throat, dry cough, fatigue, and intermittent fever of 38.5°C orally after simultaneous injection of an influenza vaccine and a dermal filler containing hyaluronic acid. Ten days later the patient developed palpitations and neck pain radiating to the left jaw. DIAGNOSIS AND INTERVENTIONS: She was diagnosed with SAT on day 16 after her first visit and responded promptly to etoricoxib treatment. OUTCOMES: The patient progressed clinically from hyperthyroidism to euthyroid state and eventually to hypothyroidism and further testing showed she had HLA B-35 haplotype. LESSONS: Physicians should be aware that SAT might be associated with the administration an influenza vaccine and this possible association might increase if the vaccine was co-administered with a dermal filler.

Subacute Thyroiditis Following SARS-CoV-2 Vaccines: Six Cases Report and Review of the Literature.

Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid that develops following viral upper respiratory tract infections. SARS-CoV-2 virus, the cause of COVID-19, binds to the Angiotensin-Converting Enzyme-2 (ACE2) molecule expressed on the target cell surface. Thyroid gland shows high levels of ACE2 expression. The cases of SARS-CoV-2-related subacute thyroiditis and Graves' disease have been reported. It has recently been noted that vaccines for SARS-CoV-2 also induce autoimmune and inflammatory reactions. We present six (4 male, 2 female) cases of SAT that developed after mRNA and inactivated SARS-CoV-2 vaccines. And we have reviewed the literature. SAT was seen in 5 patients after mRNA vaccine, in one after inactivated vaccine. Their clinic and laboratory findings suggested to SAT. They were treated with nonsteroid anti-inflamatory drugs and/or methylprednisolone.They recovered within few weeks. Out patients did not have permanent hypothyroidism after SAT. The history of SARS-CoV-2 vaccination should be questioned in patients with subacute thyroiditis in pandemic days.