Concurrent Subacute Thyroiditis and Graves' Disease After COVID-19: A Case Report.

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves' disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis.

Hyperthyroidism is a common condition with a global prevalence of 0·2-1·3%. When clinical suspicion of hyperthyroidism arises, it should be confirmed by biochemical tests (eg, low TSH, high free thyroxine [FT4], or high free tri-iodothyonine [FT3]). If hyperthyroidism is confirmed by biochemical tests, a nosological diagnosis should be done to find out which disease is causing the hyperthyroidism. Helpful tools are TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy. Hyperthyroidism is mostly caused by Graves' hyperthyroidism (70%) or toxic nodular goitre (16%). Hyperthyroidism can also be caused by subacute granulomatous thyroiditis (3%) and drugs (9%) such as amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors. Disease-specific recommendations are given. Currently, Graves' hyperthyroidism is preferably treated with antithyroid drugs. However, recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. Being younger than 40 years, having FT4 concentrations that are 40 pmol/L or higher, having TSH-binding inhibitory immunoglobulins that are higher than 6 U/L, and having a goitre size that is equivalent to or larger than WHO grade 2 before the start of treatment with antithyroid drugs increase risk of recurrence. Long-term treatment with antithyroid drugs (ie, 5-10 years of treatment) is feasible and associated with fewer recurrences (15%) than short-term treatment (ie, 12-18 months of treatment). Toxic nodular goitre is mostly treated with radioiodine (131I) or thyroidectomy and is rarely treated with radiofrequency ablation. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases. Specific attention is given to patients with hyperthyroidism who are pregnant, have COVID-19, or have other complications (eg, atrial fibrillation, thyrotoxic periodic paralysis, and thyroid storm). Hyperthyroidism is associated with increased mortality. Prognosis might be improved by rapid and sustained control of hyperthyroidism. Innovative new treatments are expected for Graves' disease, by targeting B cells or TSH receptors.

Notes for the general paediatrician: managing thyrotoxicosis in children and young people.

Thyrotoxicosis due to hyperthyroidism is a serious disorder in childhood often presenting to general paediatricians with a range of clinical manifestations. The commonest cause is Graves' disease, an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies. Early recognition and accurate interpretation of investigations are essential to achieve and maintain a euthyroid state. This will not only optimise growth, development and transition from childhood to young adult life but also avoid the potentially severe and life-threatening complications of acute thyrotoxicosis. In this review, we have focussed on the general paediatrician's perspective of the presentation and management of thyrotoxicosis and the need to network with specialist paediatric endocrine centres to optimise patient care. We have discussed nuances of therapy, side effects and long-term outcomes, while recognising that limited remission rates in this age group often necessitate more definitive management. While carbimazole is usually used as first-line medical therapy, we have provided useful information to guide paediatricians in the discussion of individualised safe and effective treatment plans for both short-term and long-term management.

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.

A rare case of grave's disease after SARS-CoV-2 vaccine: is it an adjuvant effect?

The COVID-19 virus has been responsible for the development of several systemic diseases. Recently, the COVID-19 vaccine has also been incriminated in the development of autoimmune diseases. Currently, researchers have focused on the relationship between the COVID-19 vaccine and the activation of autoimmune phenomenon. We report a case of Graves' disease (GD) whose symptoms appeared 3 days after vaccination against COVID-19. A forty-three-year-old female, without pathological history, presented with diarrhea and palpitation. She received her first SARS-CoV-2 Vaccine dose (Pfizer-BioNTech), in August 2021. Three days after the vaccine, she felt palpitations, sleep disorders, muscle weakness, and heat intolerance. On examination, her pulse was 119 beats per minute, she weighed 63 kg, and she had lost 4 kg in only two months. GD was suspected. Thyroid hormone testing showed low thyroid-stimulating hormone, and an elevated serum free thyroxine hormone T4 level. Serology tests were positive for TSH receptor autoantibodies (TRAB). A GD induced by adjuvants of SARS-CoV-2 vaccine has been retained as a final diagnosis. Several autoimmune diseases have been attributed to adjuvant-induced autoimmune/inflammatory syndrome, including systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis, and recently few cases of GD have been explained by this phenomenon.

Systematic review of COVID-19 and autoimmune thyroiditis.

COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the literature to assess the prevalence, clinical features and outcome of autoimmune thyroid disorders triggered by COVID-19. We reviewed case reports, case series, and observational studies of autoimmune thyroiditis including Graves' disease, Hashimoto thyroiditis, and silent thyroiditis developed in COVID-19 patients by searching PubMed, SCOPUS and Web of Science and included in the systematic review. Our search yielded no prevalence study. We noted 20 reported cases: Fourteen cases of Graves' disease, 5 cases of hypothyroidism due to Hashimoto's thyroiditis and one case of postpartum thyroiditis. The majority (16/20, 80%) were middle-aged (mean age: 40 years) female patients. Autoimmune thyroiditis was diagnosed either concomitantly or 7-90 days after the COVID-19 infection. Eight out of 14 cases with Graves' disease had a known thyroid disorder and they were stable in remission. One out of 5 cases with Hashimoto's thyroiditis had known prior hypothyroidism. The majority of the patients achieved remission within 3 months. One patient with thyroid storm due to Graves' disease and one patient with myxedema coma have died. Current data suggest that COVID-19 may cause autoimmune thyroid disease or exacerbate the underlying thyroid disease in remission. It is reasonable to routinely assess the thyroid functions both in the acute phase and during the convalescence so as not to overlook a thyroid disorder and not to delay treatment especially in patients with preexisting autoimmune thyroid diseases.

SARS-CoV-2 Vaccine-induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up.

CONTEXT: The number of reported cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) and Graves' disease (GD) is growing. However, active debate continues about managing such side effects and the safety of repeat or booster doses of the vaccines in such cases. OBJECTIVES: This study aims to present long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT or GD cases and provide data regarding the safety of revaccinations. METHODS: Patients diagnosed with SARS-CoV-2 vaccine-induced SAT or GD were included. Data regarding the long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT and GD cases and outcomes of repeat or booster SARS-CoV-2 vaccinations were documented. The literature, including cases of SARS-CoV-2 vaccine-induced SAT or GD, was reviewed. RESULTS: Fifteen patients with SARS-CoV-2 vaccine-induced SAT and 4 with GD were included. Pfizer/BioNTech COVID-19 vaccine (BNT162b2) was associated with symptoms in a majority of cases with SAT and all with GD. Median time from vaccination to symptom onset was 7 and 11.5 days, respectively, while 7 and 2 patients required medical treatment in SAT and GD groups, respectively. Remission was documented in 10 SAT patients, with a median time to remission of 11.5 weeks. No exacerbation/recurrence of SAT occurred in 7 of 9 patients who received a repeat vaccination dose, while symptoms of SAT worsened following the second vaccination in 2 cases. None of the patients experienced severe side effects that could be associated with revaccinations. CONCLUSIONS: Revaccinations appear to be safe in patients with SARS-CoV-2 vaccine-induced SAT cases, while more evidence is needed regarding SARS-CoV-2 vaccine-induced GD.

[Graves' Disease]. / Morbus Basedow.

DIAGNOSIS: The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb. THERAPY: Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis. PREGNANCY: The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug. IMMUNE CHECKPOINT INHIBITORS (ICI): The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

Thyrotoxicosis following SARS-COV-2 vaccination: a case series and discussion.

AIM: To describe a case series of thyrotoxicosis likely triggered by SARS-CoV-2 vaccination and to warn physicians about this potential correlation. To report clinical, laboratory and imaging findings and provide further information that goes in line with the underlying mechanisms. METHODS: Single-center case series based on all the information collected in the hospital medical records, as well as the temporal sequence between the onset of symptoms and COVID-19 vaccination. RESULTS: We report 8 cases with thyrotoxicosis after SARS-CoV-2 vaccination. 4 cases of Graves' disease (GD), 2 cases of subacute painful thyroiditis (SAT), 1 case of concurrent GD and SAT and 1 case of atypical subacute thyroiditis. Five patients received BNT162b2 mRNA vaccine, 3 patients 1273 mRNA vaccine. The onset of symptoms following vaccination ranged from 10 to 14 days in six of eight patients and from 7 to 8 weeks in two patients. CONCLUSIONS: Several hypotheses have been proposed to explain the potential correlation between SARS-CoV-2 vaccination and thyrotoxicosis, including immune system hyper-stimulation, molecular mimicry and Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA). We should pay greater attention to thyroid disorders in patients receiving vaccine against SARS-CoV-2.

Thyroid Eye Disease Following COVID-19 Vaccine in a Patient With a History Graves' Disease: A Case Report.

A 50-year-old woman with a history of controlled Graves' disease without clinical ophthalmopathy presents with 2 months of left more than right periorbital swelling and proptosis. Her eye symptoms and signs began 3 days following her second vaccination against the COVID-19 virus. Orbital imaging, elevated thyroid stimulating immunoglobulin, and negative systemic work up for other diseases were consistent with a diagnosis of active thyroid eye disease. The temporal relationship to her vaccination was likely consistent with autoimmune/inflammatory syndrome associated with adjuvants. Clinicians should remind patients of the symptoms and signs of thyroid eye disease and to seek appropriate medical and ophthalmic advice if they occur after the COVID-19 vaccine.

Recurrent Graves' disease post SARS-CoV-2 infection.

A 22-year-old woman was diagnosed with thyrotoxicosis 8 weeks after the diagnosis of a mild COVID-19 infection. She had reported significant unexplained weight loss after testing positive for COVID-19, but failed to seek medical attention. She recovered well from COVID-19, but presented to the emergency department with worsening symptoms of thyrotoxicosis after 2 months. In view of her known history of previously treated Graves' disease, a recurrence of Graves' thyrotoxicosis was suspected. A positive thyroid stimulating hormone receptor antibody confirmed the diagnosis. She was started on carbimazole and propranolol treatment with significant improvement of her symptoms.

Two Cases of Graves' Disease Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome Induced by Adjuvants.

Background: The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) comprises four entities, including the postvaccination phenomenon, which appears after being exposed to adjuvants in vaccines that increase the immune response. There is limited information about autoimmune endocrine diseases and ASIA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Patient's Findings: Two female health care workers received a SARS-CoV-2 vaccine, and three days later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone, and elevated antithyroid antibodies. Summary: Vaccines have been shown to trigger an immune response that leads to a broad spectrum of autoimmune diseases, including autoimmune thyroid disease. Our patients met the diagnostic criteria for ASIA; they were exposed to an adjuvant (vaccine), and they developed clinical manifestations of thyroid hyperfunction within a few days, with the appearance of antithyroid antibodies, despite being healthy before vaccination. Conclusion: Graves' disease can occur after SARS-CoV-2 vaccination.