Graves' disease after exposure to the SARS-CoV-2 vaccine: a case report and review of the literature.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is characterized by immune system dysregulation after exposure to adjuvants, such as aluminum. Although cases of autoimmune thyroid diseases caused by ASIA have been reported, Graves' disease is one of the rarer diseases. There are some reports that vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause ASIA. Here, we describe a case of Graves' disease following SARS-CoV-2 vaccination and a review of the literature. A 41-year-old woman was admitted to our hospital because of palpitations and fatigue. Two weeks after receiving the second SARS-CoV-2 vaccine (BNT162b2, Coronavirus Modified Uridine messenger RNA (mRNA) Vaccine, Pfizer), she developed fatigue and gradually worsened. On admission, she exhibited thyrotoxicosis (thyroid-stimulating hormone (TSH) < 0.01 mIU/L (0.08-0.54), free triiodothyronine (FT3) 33.2 pmol/L (3.8-6.3), and free thyroxine (FT4) 72.1 pmol/L (11.6-19.3)) and palpitations associated with atrial fibrillation. TSH receptor antibody (TRAb) was positive (TRAb 5.0 IU/L (< 2.0)), and 99mTc scintigraphy showed diffuse uptake in the thyroid gland, suggesting that the thyrotoxicosis in this case was caused by Graves' disease. Thiamazole was prescribed to correct her condition, and soon after this treatment was initiated, her symptoms and thyroid hormone levels were significantly reduced. This case report reinforces the potential correlation between ASIA affecting the thyroid and SARS-CoV-2 mRNA vaccines. The clinical course suggests that it is essential to consider the possibility of developing ASIA, such as Graves' disease, after exposure to the SARS-CoV-2 vaccine.

Takedani K ，Notsu M ，Ishiai N ，Asami Y ，Uchida K ，Kanasaki K ... -  《BMC Endocrine Disorders》

Development of Graves' Disease After SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review.

Background: Mounting evidence has revealed the interrelationship between thyroid and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to explain the thyroid dysfunction and autoimmune thyroid disorders observed after coronavirus disease 2019 (COVID-19). There are limited reports of thyroid dysfunction after SARS-CoV-2 vaccination. Methods: We report a case of a 40-year-old Chinese woman who developed Graves' disease after BNT162b2 mRNA vaccine. A search of PubMed and Embase databases from 1 September 2019 to 31 August 2021 was performed using the following keywords: "COVID," "vaccine," "thyroid," "thyroiditis," and "Graves." Results: A 40-year-old Chinese woman who had 8-year history of hypothyroidism requiring thyroxine replacement. Her anti-thyroid peroxidase and anti-thyroglobulin antibodies were negative at diagnosis. She received her first and second doses of BNT162b2 mRNA vaccine on 6 April and 1 May 2021, respectively. She developed thyrotoxicosis and was diagnosed to have Graves' disease 5 weeks after the second dose of vaccine, with positive thyroid stimulating immunoglobulin level, diffuse goiter with hypervascularity on thyroid ultrasonography and diffusely increased thyroid uptake on technetium thyroid scan. Both anti-thyroid peroxidase and anti-thyroglobulin antibodies became positive. She was treated with carbimazole. Literature search revealed four cases of Graves' disease after SARS-CoV-2 vaccination, all after mRNA vaccines; and nine cases of subacute thyroiditis, after different types of SARS-CoV-2 vaccines. Conclusion: Our case represents the fifth in the literature of Graves' disease after SARS-CoV-2 vaccination, with an unusual presentation on a longstanding history of hypothyroidism. Clinicians should remain vigilant about potential thyroid dysfunction after SARS-CoV-2 vaccination in the current pandemic.

Lui DTW ，Lee KK ，Lee CH ，Lee ACH ，Hung IFN ，Tan KCB ... -  《Frontiers in Public Health》

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

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. 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. 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.

Yasuda S ，Suzuki S ，Yanagisawa S ，Morita H ，Haisa A ，Satomura A ，Nakajima R ，Oikawa Y ，Inoue I ，Shimada A ... -  《BMC Endocrine Disorders》

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

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. 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. 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.

Taşkaldıran I ，Altay FP ，Bozkuş Y ，İyidir ÖT ，Nar A ，Tütüncü NB ... -  《-》

A Case Report of Conversion from Hashimoto's Thyroiditis to Graves' Disease in Type 1 Diabetic Patient Following the COVID-19 Vaccination.

A considerable number of COVID-19 vaccines became available following the outbreak. Yet, various inflammatory and autoimmune complications have been reported following vaccination. We aimed to report the case of a type 1 diabetic patient converting from Hashimoto's thyroiditis to Graves' disease after the fourth dose of COVID-19 vaccine, thought to trigger an autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). A thirty-one-year-old female patient with type 1 diabetes and Hashimoto's thyroiditis applied to our clinic with complaints of palpitations, anxiety, and weight loss one month after the fourth dose of COVID-19 vaccine (2 doses of CoronaVac + 2 doses of Pfizer/BioNTech). She was receiving levothyroxine 50 mcg/day. When her thyroid function tests showed thyrotoxicosis, we initially considered thyroxine-related exogenous thyrotoxicosis. However, we considered Graves' disease upon persisting thyrotoxicosis despite thyroxine withdrawal, positive serum TSH receptor antibody titers, and other imaging findings. Therefore, various autoimmune and inflammatory events have been reported after the COVID-19 vaccination. Adjuvants in vaccines can trigger autoimmune events, which lead to ASIA syndrome. COVID-19 vaccines may cause increased TSH receptor antibody levels or change the balance in the activity of blocking and stimulating antibodies, which may cause a conversion from Hashimoto's to Graves' disease. This was the first case report where the patient experienced a conversion from Hashimoto's to Graves' disease after COVID-19 vaccination, which may ultimately be related to ASIA syndrome. Yet, more data is needed to elucidate such a relationship, and patients should closely be checked regularly after four doses of vaccination.

Taşkaldıran I ，Altay FP ，Bozkuş Y ，İyidir ÖT ，Nar A ，Tütüncü NB ... -  《-》