Subacute Thyroiditis Research Articles

COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1β, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.

Difficulties in diagnosing subacute thyroiditis during COVID-19 pandemic

Subacute thyroiditis is an inflammatory disease of the thyroid gland. Clinical manifestations include pain or discomfort in the neck, a painful diffuse goiter, and a transient episode of hyperthyroidism. We describe the case of a 48-year-old woman who had no symptoms characteristic of subacute thyroiditis. The test results were consistent with a clinical diagnosis of secondary hypothyroidism. The patient had a history of asymptomatic COVID-19 episode 6 months ago and neck pain one month ago. This case demonstrates the importance of a detailed history, comprehensive examination, and correct interpretation of laboratory and instrumental findings in making the diagnosis.

SARS-COV-2 specific t-cells in patients with thyroid disorders related to COVID-19 are enriched in the thyroid and acquire a tissue-resident memory phenotype

BackgroundSARS-CoV-2 infections have been associated with the onset of thyroid disorders like classic subacute thyroiditis (SAT) or atypical SAT upon severe COVID disease (COV-A-SAT). Little is known about thyroid anti-viral immune responses. ObjectivesTo define the role of T-cells in COV-A-SAT. MethodsT-cells from COV-A-SAT patients were analyzed by multi-dimensional flow cytometry, UMAP and DiffusionMap dimensionality reduction and FlowSOM clustering. T-cells from COVID-naïve healthy donors, patients with autoimmune thyroiditis (ATD) and with SAT following COVID vaccination were analyzed as controls. T-cells were analyzed four and eight months post-infection in peripheral blood and in thyroid specimen obtained by ultrasound-guided fine needle aspiration. SARS-COV2-specific T-cells were identified by cytokine production induced by SARS-COV2-derived peptides and with COVID peptide-loaded HLA multimers after HLA haplotyping. ResultsCOV-A-SAT was associated with HLA-DRB1*13 and HLA-B*57. COV-A-SAT patients contained activated Th1- and cytotoxic CD4+ and CD8+ effector cells four months post-infection, which acquired a quiescent memory phenotype after eight months. Anti-SARS-CoV-2-specific T-cell responses were readily detectable in peripheral blood four months post-infection, but were reduced after eight months. CD4+ and CD8+ tissue-resident memory cells (TRM) were present in the thyroid, and circulating CXCR3+T-cells identified as their putative precursors. SARS-CoV-2-specific T-cells were enriched in the thyroid, and acquired a TRM phenotype eight months post-infection. ConclusionsThe association of COV-A-SAT with specific HLA haplotypes suggests a genetic predisposition and a key role for T-cells. COV-A-SAT is characterized by a prolonged systemic anti-viral effector T-cell response and the late generation of COVID-specific TRM in the thyroid target tissue.

Subacute thyroiditis following Mpox infection in a patient with human immunodeficiency virus.

Mpox (MPX) formerly known as monkeypox was declared a public health emergency of international concern, following an outbreak that commenced in May 2022. We report a case of subacute thyroiditis following MPX infection. To our knowledge, it is the first documented incidence of this complication in humans. A 51-year-old male, with a well-controlled human immunodeficiency virus (HIV) infection on antiretroviral therapy, was reviewed 3 weeks after a positive test for MPX. The acute skin lesions and initial systemic symptoms had resolved, but he described significant neck discomfort, fatigue, weight loss and night sweats. Blood tests showed a raised C-reactive protein, free T4 and suppressed thyroid-stimulating hormone. His thyroid antibodies were negative. He was treated initially with carbimazole and propranolol, pending exclusion of any other intercurrent infection. A chest radiograph was normal; blood cultures and a combined nose and throat swab for respiratory virus PCR testing were negative. Following this, he commenced a 2-week course of prednisolone; his symptoms resolved completely within 24 h of starting. He subsequently developed hypothyroidism, which was treated with levothyroxine. The clinical features, abnormal thyroid function, raised CRP and negative thyroid antibodies 3 weeks post-MPX positive test was consistent with viral subacute thyroiditis. This case demonstrates that, as described following other viral infections, MPX can cause subacute thyroiditis, which follows a similar course to the classic form of subacute thyroiditis. Clinicians should be aware of this potential endocrine complication when attending to patients with MPX. Subacute thyroiditis can present following mpox virus infection. Its course is similar to the classic form of subacute thyroiditis and steroids are effective. It is important to exclude other concurrent infections prior to starting steroids, especially for patients who are immunosuppressed or in other high-risk groups.

Emodin Alleviates the Th17/Treg Imbalance by Targeting Myd88/NF-κB Signaling in Subacute Thyroiditis

Emodin Alleviates the Th17/Treg Imbalance by Targeting Myd88/NF-κB Signaling in Subacute Thyroiditis

The value of FT4/TSH ratio in the differential diagnosis of Graves' disease and subacute thyroiditis.

To explore the value of the FT4/TSH ratio in the etiological diagnosis of newly diagnosed patients with thyrotoxicosis. The retrospective study was conducted on 287 patients with thyrotoxicosis (122 patients with subacute thyroiditis and 165 patients with Graves' disease) and 415 healthy people on their first visit to our hospital. All patients underwent thyroid function tests including the measurement of T3, T4, FT3, FT4, TSH, T3/TSH, and T4/TSH. The receiver operating characteristic (ROC) curve was employed to evaluate the value of FT4/TSH in the differential diagnosis of Graves' disease and subacute thyroiditis, and compared with other related indicators. The area under the curve of FT4/TSH for diagnosing Graves' disease and thyroiditis was 0.846, which was significantly larger than the area under the curve of T3/T4 ratio (P< 0.05) and FT3/FT4 ratio (P< 0.05). When the cut-off value of the FT4/TSH ratio was 5731.286 pmol/mIU, the sensitivity was 71.52%, the specificity was 90.16%, the positive predictive value was 90.77% and the negative predictive value was 70.06%. The diagnostic accuracy was 79.44%. FT4/TSH ratio can be used as a new reference index for the differential diagnosis of thyrotoxicosis.

Vitamin D Level Among Patients with Different Thyroid Diseases

To investigate the differences in vitamin D levels in patients with different types of thyroid disease and to investigate the factors influencing vitamin D levels in patients with thyroid disease, this study collected clinical data from 1603 patients with thyroid disease attending the Department of Endocrinology and Metabolism of the First People's Hospital of Yunnan Province and conducted a retrospective cross-sectional study. The clinical data of 1603 patients with thyroid diseases including Graves' disease (GD), subacute thyroiditis (SAT), autoimmune thyroid disease (AITD) and hypothyroidism (HP) were collected from the Department of Endocrinology and Metabolism of yunnan First People's Hospital. Gender, age, BMI, blood lipids, thyroid hormones, thyroid autoantibodies, and serum 25-hydroxyvitamin D(25(OH)D) levels were measured. Results: (1) The level of 25(OH)D in patients with different thyroid diseases was from high to low, in the following order: GD group (29.54±7.54 ng/ml), SAT group (28.01±7.14 ng/ml), AITD group (26.97±6.58 ng/ml), HP group (25.88±6.75 ng/ml), the differences were statistically significant (P<0.05). The 25(OH)D level in GD group was significantly higher than that in other groups (P<0.05), while the 25(OH)D level in HP group was significantly lower than that in SAT group (P<0.05). (2) The changing trend of thyroid hormone levels (T3, FT3 and FT4) was consistent with that of 25(OH)D (P <0.005). (3) 25(OH)D was established as the dependent variable with multiple linear regression equation, Y = 3.80 gender + 0.058FT3-0.036 age + 28.122(female as control group). Conclusions: There were significant differences in vitamin D levels among patients with thyroid diseases, with the highest vitamin D level in GD patients and the lowest vitamin D level in HP patients. The higher the thyroid hormone level, the higher the 25(OH)D, which may be related to the strength of the immune response or the effect of thyroid hormone on vitamin D synthase. Male and high levels of FT3 were associated with increased 25(OH)D levels in thyroid patients.

Challenging Thyroid Cases in Clinical Practice

Thyroid disorders are prevalent, and their manifestations are divergent and sometimes it is very challenging to diagnose and deal with some Thyroid cases in clinical practice. Here seven different challenging cases will be discussed that will help clinicians to diagnose and treat such cases in dayto- day clinical practice. First case enlightened us that Thyroid function should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction, since there are many other factors in acutely or chronically ill euthyroid patients that influence thyroid function tests. The second case taught us that there is assay interference with Biotin ingestion and patients taking Biotin should hold the supplement for two days prior to assessing thyroid function. Subacute thyroiditis is a self-limiting inflammatory condition of the thyroid gland and COVID-19 virus infection may be associated with subacute thyroiditis as a complication that may occur in patients without any previous thyroid disorder that is revealed in third case. In Secondary hypothyroidism/Hypopituitarism, TSH may be low, normal, or even slightly elevated due to inactive TSH isoform in blood. The fourth case shows us that only TSH testing in clinical practice leads to missing Secondary hypothyroidism/Hypopituitarism. Learning from fifth case is that during monitoring of thyrotoxic patients taking ATDs, serum TSH may remain suppressed for several months after starting therapy and it is therefore not a good parameter for monitoring therapy early during treatment, rather we should rely on FT4 and FT3. The sixth case enlightened us that in case of low TSH in early pregnancy, Gestational transient Thyrotoxicosis should be excluded which is commonly associated with hyperemesis gravidarum with no prior history of thyroid disease, no stigmata of Graves’ disease (Goiter, ophthalmopathy) and a self-limited mild disorder. In poorly compliant patients, there may be a combination of high FT4 and high TSH that is revealed in the seventh case. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 189

A Case Report of COVID-19 and Subacute Thyroiditis in Fars, Iran

Background &amp; Objective: COVID-19 can affect thyroid gland and causes subacute thyroiditis.&#x0D; Case Presentation: We introduced a 60-year-old woman with an initial symptom of anterior cervical pain without any other constitutional symptoms. Nasopharyngeal and oropharyngeal swabs were detected positive for COVID-19 using RT-PCR assay. According to ultrasonographic, laboratory (lowered TSH, elevated CRP and ESR), and physical findings, subacute thyroiditis was found following the SARS-CoV-2 infection.&#x0D; Conclusion: As subacute thyroiditis associated with SARS-Cov-2 may be represented without any fever, ruling out this infection in these patients is considerable.

Graves' disease presented simultaneously with subacute thyroiditis - A case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Clinical, Laboratory and Imaging Findings in the Selection of Treatment and Determination of Relapse in Subacute Thyroiditis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A Rare Case of Covid-19 Vaccine-Associated Subacute Thyroiditis Causing Thyroid Storm

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Subacute thyroiditis development and its clinical course are HLA-dependent

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Case of Subacute Thyroiditis after receiving the SARS-CoV-2 vaccine and the Covid-19 infection 6 months later in the same patient

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Paraneoplastic Subacute Thyroiditis Secondary to Renal Cell Carcinoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1405060: Subacute Thyroiditis Following Vaccination with COVID-19 mRNA Vaccine

Subacute thyroiditis is a self-limiting post-viral inflammatory disorder occurring in 3 phases (hyper-, hypo-, and euthyroidism) Post-vaccine thyroiditis has also been reported, but is rare. A 36-year-old Emirati female presented to our clinic with generalized fatigue, mild to moderate vague neck pain, intermittent palpitations, and loss of appetite 2 weeks after receiving her first dose of Pfizer-BioNTech mRNA vaccine against COVID-19. Clinical examination findings and laboratory test results were consistent with subacute thyroiditis. Patient is a mother of 5 healthy children, youngest is breast-fed infant (11 months old). There was no history suggestive of postpartum thyroiditis and no family history of thyroid dysfunction. Physical examination at initial visit showed mild tachycardia, and a normal blood pressure. She weighed 66 kg. Thyroid function tests revealed a suppressed TSH of 0.011 μIU/mL, high Free T4 of >100 pmol/l), and Free T3 FT3 of 29.6 pmol/L. Both TSH receptor antibodies, and Thyroid antibodies (TPO) were negative. Thyroid scintigraphy showed decreased uptake in both lobes. Thyroid ultrasound showed hypoechoic heterogeneous echotexture of the thyroid gland with vascular conglomerate and micro-calcification, along with normal sized reactive lymph nodes at sternal angle. Symptoms aggravated through the next week; patient dropped 3kg of her body weight and her palpitations increased, with a recorded resting heart rate between 120-130 beats/min. TSH decreased to 0.001μIU/mL while FT4 remained high, with an improvement to 90 pmol/L. Subsequently, the patient started to regain weight. Palpitations improved within a month. She developed a biochemically hypothyroid picture followed by clinical and biochemical euthyroidism after one more month. Second dose of the vaccine was uneventful. Last evaluation was 10 months later; TSH, FT3 and FT4 were all in normal range, acute-phase reactants were completely normal and in complete remission. The exact mechanism for post-vaccination subacute thyroiditis remains unknown, vaccine adjuvants may induce diverse autoimmune and inflammatory reaction. Subacute thyroiditis has rarely been reported with other COVID-19 vaccines contains no Polyethylene glycol (PEG). A possible cross-reactivity between thyroid cell antigens and spike protein of the coronavirus produced by mRNA vaccines might be responsible. Further research is needed to investigate the incidence of subacute thyroiditis in COVID-19 pandemic days.

Abstract #1408165: An Atypical Case of Subacute Thyroiditis Presenting as a Toxic Adenoma

Subacute thyroiditis is inflammation of the thyroid gland often occurring after a viral infection of the upper respiratory tract. It is an uncommon condition mostly seen in women compared to men and is characterized by neck pain, a tender thyroid on exam with hyperthyroidism on initial presentation and low uptake on radioiodine imaging. A 36-year-old American Indian female with no significant past medical history was referred to Endocrinology for a new diagnosis of hyperthyroidism and for fine needle aspiration of thyroid nodules. Four months prior the patient was experiencing intermittent palpitations along with right sided neck pain. A thyroid ultrasound ordered by her primary care provider showed multiple nodules, including a 1.9 cm heterogeneous nodule with eccentric calcifications in the left lower lobe (TI-RADS 4) and a 2.7 cm right hypoechoic solid nodule with ill-defined borders, taller than wide (TI-RADS 5). Her thyroid function tests revealed a TSH < 0.025 uIU/mL (nl 0.450-4.50 uIU/mL), FT4 2.64 ng/dL (nl 0.82-1.7 ng/dL), FT3 6.4 pg/mL (nl 2.0-4.4 pg/mL) and thyroglobulin antibody < 1.0 IU/ml. A radioactive iodine uptake and scan showed decreased 24-hour uptake with a single hyperfunctioning nodule in the left thyroid lobe. The patient was started on methimazole 10 mg daily which was titrated down to 5 mg daily with normalization of her thyroid function after 3 months of treatment. Repeat thyroid function at the time of her endocrine clinic visit 1 month later revealed hypothyroidism. We performed a bedside ultrasound which did not show any thyroid nodules and the biopsy was cancelled. These findings were supported by a formal thyroid ultrasound a few weeks later. Methimazole was stopped and thyroid function normalized. Further history revealed the patient was experiencing symptoms of an upper respiratory tract infection a few weeks prior to the start of the palpations and neck pain. Six months after initial presentation, thyroid function has remained normal off methimazole. This is a rare case of subacute thyroiditis with initial findings of a toxic adenoma. To our knowledge there is only one other reported case of this unusual presentation of subacute thyroiditis with focal radioiodine uptake and thyroid nodules that later resolved on repeat imaging. This case should raise awareness for other providers to consider subacute thyroiditis when evaluating patients presenting with hyperthyroidism and atypical imaging findings. The history and clinical presentation were key in making the clinical diagnosis.

Abstract #1406613: Recurrent Thyroiditis in a Patient with Multiple sclerosis on Natalizumab

Thyroiditis, or self-limiting inflammation of the thyroid gland consists of 3 phases: hyperthyroidism, from release of hormone from damaged cells; hypothyroidism, when thyroid stores are depleted and euthyroidism with restoration of thyroid function. Etiology can include infectious, drug-induced or autoimmune causes such as multiple sclerosis (MS). In fact, 20-25% of untreated MS patients have autoimmune thyroiditis [1]. Moreover, drugs used to treat MS such as alemtuzumab and interferon have been reported to cause thyroid disease [2]. A 42-year-old female with MS on natalizumab for 10 years presented with right sided neck pain radiating to her jaw for 3 months and difficulty swallowing. Family history was pertinent for hypothyroidism in her father, and MS in her brother. She was exposed to nuclear radiation at age 3 from the Chernobyl disaster. On presentation, vital signs and physical exam were unremarkable. Thyroid ultrasound noted an ill-defined 4.2X1.3X1.9 cm hypoechoic nodule in the right mid-pole. Fine needle aspiration of the nodule showed subacute granulomatous thyroiditis (SAH). Labs showed TSH 0.02mIU/L [0.4-4.5], FT4 1.5ng/dL [0.8-1.8] and elevated total T3 204ng/dL [76-181]. TSI< 89 [140%]. Naproxen was given for pain control. Repeat labs 1 month later showed TSH 0.83mIU/L, FT4 1.1 ng/dL and total T3 196ng/dL, consistent with resolution of thyroiditis and clinically correlated with resolution of her pain. However, a month later she presented with worsening left sided neck pain and left thyromegaly associated with speech difficulty, diaphoresis, and constipation. Repeat thyroid ultrasound showed decreased size of right thyroid nodule 1.1X1.1X0.9cm and findings consistent with thyroiditis. She was treated with prednisone with complete resolution of symptoms. Labs post treatment showed elevated TSH 6.01mIU/L, total T3 106ng/dL, and FT4 0.8ng/dL consistent with the recovery phase of thyroiditis. Anti-TPO antibody level was < 1 [< 9 IU/mL]. Labs 1 month later showed normal TSH and FT4 levels. Natalizumab, a humanized monoclonal antibody commonly used to treat MS, has rarely been associated with thyroid disease. Alterations in thyroid function are thought to be due to direct toxicity on the thyroid, its blood supply or indirectly mediated by the immune system [2]. Although MS can be associated with thyroiditis, our patient did not present with the typical pattern of thyroiditis. Instead, she reported symptoms consistent with inflammation of one lobe of thyroid followed by resolution, and thereafter developed inflammation and pain of the other lobe, raising suspicion of potential involvement of natalizumab due to her atypical presentation.

Abstract #1399287: New-Onset Thyroid Eye Disease After COVID-19 Infection in Patient with Graves’ Disease Post-Radioactive Iodine Treatment

Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system and abnormal thyroid function. The aim of this novel case report is to inform physicians of the possibility that COVID-19 infection may precipitate thyroid eye disease (TED) in patients with Graves’ Disease (GD) even after treatment with radioactive iodine (RAI). In this report, we describe a patient with GD treated with RAI who developed TED after COVID-19 infection. The patient was initially diagnosed with GD in 2018. A thyroid uptake scan (I-123) was consistent with GD with moderately elevated uptake. She was initially managed with methimazole and atenolol and was eventually treated with RAI (16.32 millicurie I-131) in February 2021. She had post-ablative hypothyroidism managed with levothyroxine. The patient contracted COVID-19 in January 2022. In February 2022, the patient started experiencing eye irritation, dryness, protrusion of eyes, eyelid swelling, and visual disturbances. Thyroid stimulating hormone (TSH) receptor auto-antibodies (7.33 IU/L, normal < /=1.00 IU/L) and thyroid stimulating immunoglobulin (4.30 IU/L, normal < /=1.00 IU/L) were elevated. TSH was normal (2.180 mIU/L, normal 0.270 - 4.200 mIU/L) on levothyroxine 125 mcg daily. She was later diagnosed with TED. GD is an autoimmune thyroid disorder related to the presence of TSH receptor-stimulating antibodies and is often associated with ocular symptoms. Activation of an autoimmune response during COVID-19 infection, may induce onset or relapse of GD. A study using the national health insurance service database in South Korea noted an increase in the incidence of subacute thyroiditis in 2020 in association with the COVID-19 pandemic. TED is usually seen in patients with GD. Radioactive iodine is widely used in the treatment of GD and has been associated with development or worsening of TED. There are published cases of TED occurring in patients with GD after receiving COVID-19 vaccine. It is thought that the inflammatory syndrome induced by the adjuvants could induce molecular mimicry, which could trigger TED. In most cases this adverse effect was transient, lasting a few months after treatment. There have been case reports of TED occurring after 3 to 21 days of COVID-19 vaccination in patients with controlled GD. Symptoms improved in 4-8 months. Development of TED in patients with GD who have been treated with RAI typically occurs soon after RAI therapy. For TED to occur in a GD patient 11 months after receiving RAI therapy is unusual. COVID-19 infection appears to have been the trigger for this patient's eye disease. This is highly unusual and has not been published to our knowledge.

Evaluation of thyroid function in people vaccinated against COVID-19 via Sinofarm type

Background; Since the emergence of the coronavirus disease pandemic, several effective vaccines have been introduced. These vaccines work through several different immunogenic pathways to produce effective immunity. There have been a number of reports of patients developing sub-acute thyroiditis and thyroid dysfunction after receiving the coronavirus (COVID-19) vaccine. This study aims to demonstrate the physiological effect of the covid -19 vaccine on human thyroid hormone. Methodology; For this purpose, 25 samples of male and female blood from people vaccinated with the corona virus used, 25 samples of blood from unvaccinated people were considered as a control group. The effect of this vaccine on the functions of the thyroid gland and on the concentrations of hormones was shown. A significant increase in the concentration of hormone T4 was observed in the group of vaccinated people compared to the control group. Conclusion, the current study Showed that the level of hormones increased significantly in the vaccinated compared to the control group, as well as concluded these results was indicate that thyroid function is negatively affected by the vaccine.