Painless Thyroiditis Research Articles

Thyroiditis Should be Listed Among Adverse Effects of Covid-19 Vaccination

Background: Several cases of thyroiditis were recently reported in individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19). Objective: To determine characteristics of thyroiditis occurring following SARS-CoV-2 vaccination. Methods: PubMed search up to April 26, 2022. Search terms are thyroiditis, SARS-Cov-2, vaccine, COVID-19. Case reports, case series, review articles and pertinent in vitro studies in English, Spanish and French are reviewed. Results: Review of literature revealed 97 patients with thyroiditis (71.3% women, age range 26-82 year-old) occurring following vaccination against SARS-CoV-2. Subjects reported from Turkey alone contributed to 50.5% of all cases. Seven cases (7.2%) presented with silent (painless) thyroiditis. Onset of thyroiditis symptoms ranged from 12 hours to 12 weeks after vaccination. In 74.2% of patients, these symptoms started between 3 to 15 days post-vaccination. The most frequently implicated vaccine was Pfizer-BioNTech vaccine (55.7% of cases) followed by CoronaVac (21.6%), Moderna (8.5%) and AstraZeneca (6.1%). Thyroiditis cases were equally triggered after the first and second vaccine dose. Personal and family history of thyroid diseases and autoimmune diseases were uncommon (<5%). Among 7 patients who were re-vaccinated, 5 did not have relapse of thyroiditis, whereas 2 subjects had recurrence or worsening of thyroiditis symptoms. Clinical picture and course of thyroiditis induced by the vaccine generally mimic those of non-vaccine-related classic thyroiditis. Mechanisms of thyroiditis after COVID-19 vaccination are unclear but there is evidence of genetic predisposition related to specific human leukocyte antigens (HLA) haplotypes. Glucocorticoid therapy of thyroiditis may virtually decrease COVID-19 vaccine immunogenicity. Conclusion: Thyroiditis should be listed among adverse effects of COVID-19 vaccines to alert physicians and avoid misdiagnosis and unnecessary investigations. If possible, it may be better to avoid its treatment with glucocorticoids.

Concomitant myocarditis and painless thyroiditis after AstraZeneca coronavirus disease 2019 vaccination: a case report

BackgroundIncidence of myocarditis following messenger RNA coronavirus disease 2019 vaccination has been widely described, but this clinical scenario after adenoviral vector coronavirus disease 2019 vaccination has only been rarely reported. In addition, a few case reports of thyroiditis after adenoviral vector coronavirus disease 2019 vaccination have been published.Case presentationA 55-year-old Thai woman presented with palpitation without neck pain 14 days after receiving AstraZeneca coronavirus disease 2019 vaccination. Electrocardiography revealed sinus tachycardia. Her blood tests showed elevation of cardiac troponin and free triiodothyronine with suppressed serum thyroid stimulating hormone, reflecting a hyperthyroid status. Evidence of myocardial inflammation and necrosis from cardiac magnetic resonance imaging supported the diagnosis of recent myocarditis. Laboratory results and imaging findings were consistent with thyroiditis. After 3 weeks of symptomatic treatment, her symptom and blood tests had returned to normal.ConclusionsThis case demonstrates that the adenoviral vector coronavirus disease 2019 vaccine could possibly cause myocarditis and painless thyroiditis. Clinicians should have a high index of suspicion and promptly evaluate these conditions, despite minimal symptoms.

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

PurposeThe 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.MethodsA comprehensive search within electronic databases was performed to collect reports of thyroid disorders after vaccination with COVID-19 vaccines.ResultsAmong 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.

Abstract 8: Thyroid amyloidosis presenting as persistent painless thyroiditis

Case Report: A 34-year-old patient with ESRF, found to have hereditary-amyloidosis, was referred with low TSH: 0.112 (0.340-4.250 micIU/mL), low FT3: 1.77 (2.40-4.20 pg/mL) and normal FT4:1.49 (0.80-2.30 ng/dL) in May 2018. Clinically asymptomatic, euthyroid and no goitre; was diagnosed “Sick-Euthyroid-Syndrome”. He underwent renal transplant in August 2018; his subsequent treatment included Prednisolone 20mg daily and immunosuppressants. On follow-up, his TSH was 0.303 in Oct 2018. Over next year, he had persistently low TSH: 0.005-0.196, with normal FT3, but elevated FT4: 2.39-5.21. His clinical-features varied from being asymptomatic to developing mild thyrotoxicosis. ESR: normal, Thyroid-antibodies negative, USG showed diffuse thyroid and repeated Technetium-99 scans revealed ‘gross thyroiditis’. He was managed on beta-blockers and ongoing Prednisolone. His health deteriorated since late 2019, with multiple episodes of pancreatitis due to pancreatic-duct-stones and stricture. He returned back in 2021 with neck-swelling; non-tender large-goitre with multiple nodules. TFT: low TSH, high FT4 and normal FT3. USG revealed bulky thyroid with few nodules; FNAC suggested Amyloid. He underwent Total Thyroidectomy; Histopathology confirmed ‘Amyloidosis’. Conclusion: Our patient had chronic painless thyroiditis and his steroid-therapy for post-transplant-immunosuppression probably masked the thyrotoxic-features. USG-thyroid indicated gradual structural changes, and TFT suggested possible impaired peripheral conversion of T4 to T3.

Prediction model of Graves' disease in general clinical practice based on complete blood count and biochemistry profile.

Although untreated Graves' disease (GD) is associated with a higher risk of cardiac complications and mortality, there is no well-established way to predict the onset of thyrotoxicosis in clinical practice. The aim of this study was to identify important variables that will make it possible to predict GD and thyrotoxicosis (GD + painless thyroiditis (PT)) by using a machine-learning-based model based on complete blood count and standard biochemistry profile data. We identified 19,335 newly diagnosed GD patients, 3,267 PT patients, and 4,159 subjects without any thyroid disease. We built a GD prediction model based on information obtained from subjects regarding sex, age, a complete blood count, and a standard biochemistry profile. We built the model in the training set and evaluated the performance of the model in the test set by using the artificial intelligence software Prediction One. Our machine learning-based model showed high discriminative ability to predict GD in the test set (area under the curve [AUC] 0.99). The main contributing factors to predict GD included age and serum creatinine, total cholesterol, alkaline phosphatase, and total protein levels. We still found high discriminative ability even when we restricted the variables to these five most contributory factors in our prediction model (AUC 0.97) built by using artificial intelligence software showed high GD prediction ability based on information regarding only five factors.

Myxoedema coma caused by immunotherapy-related thyroiditis and enteritis.

SummaryThyroid dysfunction is among the most common immune-related adverse reactions associated with immune checkpoint inhibitors. It most commonly manifests as painless thyroiditis followed by permanent hypothyroidism. This usually causes mild toxicity that does not interfere with oncological treatment. In rare instances, however, a life-threatening form of decompensated hypothyroidism called myxoedema coma may develop. We present a case of myxoedema coma in a woman in her sixties who was treated with a combination of CTLA-4 and PD-1 immune checkpoint inhibitors; for stage four malignant melanoma. She became hypothyroid and required thyroxine replacement after an episode of painless thyroiditis. Six months after the initial diagnosis of malignant melanoma, she presented to the emergency department with abdominal pain, profuse diarrhoea, lethargy and confusion. She was drowsy, hypotensive with a BP of 60/40 mmHg, hyponatraemic and hypoglycaemic. Thyroid function tests (TFTs) indicated profound hypothyroidism with a TSH of 19 mIU/L, and undetectable fT3 and fT4, despite the patient being compliant with thyroxine. She was diagnosed with a myxoedema coma caused by immune-related enteritis and subsequent thyroxine malabsorption. The patient was treated with i.v. triiodothyronine (T3) and methylprednisolone in the ICU. While her clinical status improved with T3 replacement, her enteritis was refractory to steroid therapy. A thyroxine absorption test confirmed persistent malabsorption. Attempts to revert to oral thyroxine were unsuccessful. Unfortunately, the patient’s malignant melanoma progressed significantly and she passed away four months later. This is the first reported case of myxoedema coma that resulted from two distinct immune-related adverse reactions, namely painless thyroiditis and enterocolitis.Learning pointsMyxoedema coma, a severe form of decompensated hypothyroidism is a rare immunotherapy-related endocrinopathy.Myxedema coma should be treated with either i.v. triiodothyronine (T3) or i.v. thyroxine (T4).Intravenous glucocorticoids should be co-administered with thyroid hormone replacement to avoid precipitating an adrenal crisis.Thyroid function tests (TFTs) should be monitored closely in individuals with hypothyroidism and diarrhoea due to the risk of thyroxine malabsorption.A thyroxine absorption test can be used to confirm thyroxine malabsorption in individuals with persistent hypothyroidism.

The emerging role of transcription factor FOXP3 in thyroid cancer.

Transcription factor FOXP3 is a crucial regulator in the development and function of regulatory T cells (Treg) that are essential for immunological tolerance and homeostasis. Numerous studies have indicated the correlation of tumor infiltrating FOXP3+ Treg upregulation with poor prognostic parameters in thyroid cancer, including lymph node metastases, extrathyroidal extension, and multifocality. Most immune-checkpoint molecules are expressed in Treg. The blockage of such signals with checkpoint inhibitors has been approved for several solid tumors, but not yet for thyroid cancer. Thyroid abnormalities may be induced by checkpoint inhibitors. For example, hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm are more frequently associated with anti-PD-1 antibodies (pembrolizumab and nivolumab). Therefore, Targeting FOXP3+ Treg may have impacts on checkpoint molecules and the growth of thyroid cancer. Several factors may impact the role and stability of FOXP3, such as alternative RNA splicing, mutations, and post-translational modification. In addition, the role of FOXP3+ Treg in the tumor microenvironment is also affected by the complex regulatory network formed by FOXP3 and its transcriptional partners. Here we discussed how the expression and function of FOXP3 were regulated and how FOXP3 interacted with its targets in Treg, aiming to help the development of FOXP3 as a potential therapeutic target for thyroid cancer.

Coronavirus Disease 2019 and the Thyroid - Progress and Perspectives.

SARS-CoV-2 infection (COVID-19) is currently a tremendous global health problem. COVID-19 causes considerable damage to a wide range of vital organs most prominently the respiratory system. Recently, clinical evidence for thyroidal insults during and after COVID-19 has been accumulated. As of today, almost all non-neoplastic thyroid diseases, i.e., Graves’ disease, Hashimoto’s thyroiditis, subacute, painless and postpartum thyroiditis, have been reported as a complication of COVID-19, and causality by the virus has been strongly implicated in all of them. Similar thyroid problems have been reported in the past with the SARS-CoV outbreak in 2002. In this review, we briefly look back at the reported evidence of alteration in thyroid functionality and thyroid diseases associated with SARS-CoV and then proceed to examine the issue with COVID-19 in detail, which is then followed by an in-depth discussion regarding a pathogenetic link between Coronavirus infection and thyroid disease.

A case of thyrotoxicosis-induced anemia in a patient with painless thyroiditis

BackgroundThere have been several reports of secondary anemia associated with Graves’ disease. There are no reports of secondary anemia resulting from thyrotoxicosis due to painless thyroiditis (silent thyroiditis). We report the case of a patient with pancreatic diabetes who developed anemia caused by thyrotoxicosis due to painless thyroiditis.Case presentationThe patient was a 37-year-old man who visited the hospital complaining of fatigue, palpitations, and dyspnea. His hemoglobin was 110 g/l (reference range, 135–176), and mean corpuscular volume was 81.5 fl (81.7–101.6). His free thyroxine (FT4) was high, at 100.4 pmol/l (11.6–21.9); the free triiodothyronine (FT3) was high, at 27.49 pmol/l (3.53–6.14); TSH was low, at < 0.01 mIU/l (0.50–5.00); and TSH receptor antibody was negative. Soluble IL-2 receptor (sIL-2R) was high, at 1340 U/ml (122–496); C-reactive protein (CRP) was high, at 6900 μg/l (< 3000); and reticulocytes was high, at 108 109 /l (30–100). Serum iron (Fe) was 9.5 (9.1–35.5), ferritin was 389 μg/l (13–401), haptoglobin was 0.66 g/l (0.19–1.70. Propranolol was prescribed and followed up. Anemia completely disappeared by 12 weeks after disease onset. Thyroid hormones and sIL-2R had normalized by 16 weeks after onset. He developed mild hypothyroidism and was treated with L-thyroxine at 24 weeks.ConclusionsThis is the first case report of transient secondary anemia associated with thyrotoxicosis due to painless thyroiditis. The change in sIL-2R was also observed during the clinical course of thyrotoxicosis and anemia, suggesting the immune processes in thyroid gland and bone marrow.

Painless Thyroiditis Presenting with Headache.

Although headache attributed to hypothyroidism is coded within The International Classification of Headache Disorders, 3rd edition, an association between headache and thyrotoxicosis (hyperthyroidism) is mentioned only in the appendix. Reports on relevant cases are too scarce to establish a causal relationship. A young man with a history of migraine with aura arrived at our headache clinic with a 10-day history of headache and weight loss. Brain MRI revealed normal findings. Blood tests revealed thyrotoxicosis. A test for thyroid-related antibodies was negative. Thus, the patient was diagnosed with painless thyroiditis. The patient's headache resolved as his thyroid hormone levels decreased. To the best of our knowledge, this is the first reported case of headache exaggerated by painless thyrotoxicosis.

Free triiodothyronine to free thyroxine ratio in the differential diagnosis of thyrotoxicosis and hyperthyroidism: A retrospective study.

Thyroid ultrasound, thyroid scintigraphy and radioactive iodine uptake (RAIU) tests are helpful in the differential diagnosis of thyrotoxicosis and hyperthyroidism. In the setting where these techniques are unavailable or unusable more accessible, and cheaper techniques would be helpful. We evaluated the capability of free triiodothyronine to free thyroxine ratio (FT3/FT4) to differentiate Graves' Disease (GD) and destructive thyroiditis (DT). In total, 318 patients with GD and 140 patients with DT were included in the study. Patients were assigned to two groups: GD and DT (subacute thyroiditis, painless thyroiditis, postpartum thyroiditis). Serum thyroid-stimulating hormone (TSH), FT4, FT3 levels and FT3/FT4 ratio were evaluated in each group. To obtain the optimal diagnostic cut-off value of FT3, FT4 and FT3/FT4 ratio, ROC curve analysis was performed of all untreated thyrotoxicosis patients. The optimal FT3/FT4 ratio cut-off value was 2.96, with a sensitivity of 71.7%, the specificity of 88.6%. The area under the ROC curve of the FT3/FT4 ratio regarding the diagnosis of GD was 0.864 (95% CI: 0.830-0.894). The cut-off level of FT3 for GD was determined as 6.6pg/mL which had a sensitivity of 72.3% and specificity of 68.6% (AUC=0.771 P<.001). The cut-off level of FT4 for GD was determined as 3.65ng/dl with a sensitivity of 35.5% and specificity of 83.6% (AUC=0.615 P<.001). When a high specificity is needed, FT3/FT4 cut-off value increases to 3.63 with 99.3% specificity and 36.5% sensitivity. FT3/FT4 ratio helps distinguish GD and DT. In cases of situations where RAIU/scintigraphy and TRAb cannot be studied, the FT3/FT4 ratio is a viable diagnostic tool. Cut-off values with higher specificity can be more helpful in differential diagnosis of GD.

Clinical Studies on Potassium Iodide-induced Painless Thyroiditis in 11 Graves' Disease Patients.

Objective Painless thyroiditis (PT) is characterized by transient hyperthyroidism with a low 99mTc uptake. We herein describe 11 cases of PT that occurred during treatment with potassium iodide (KI) for Graves' disease (GD). Methods From August 2016 to December 2018, 11 women with GD who developed PT during treatment with KI were enrolled. Of these patients, 10 discontinued antithyroid drug (ATD) because of side effects and began KI, and 1 patient switched from thiamazole to KI because she was planning a pregnancy. The mean patient age was 40.1 years old. Thyroid function tests, thyroid autoantibodies including anti thyroglobulin antibody (TgAb), anti-thyroperoxidase antibody (TPOAb), and M22-TRAb, and the 99mTc uptake were evaluated at the time of PT. Results All 11 women patients presented with transient thyrotoxicosis in which 99mTc scans revealed a low uptake of 0.34±0.15% (normal 0.70-1.02%). M22-TRAb was absent in all cases except for one (2.4 IU/L), whereas TgAb and TPOAb were present in 10 and 6 cases, respectively. Ten patients returned to a euthyroid status without passing through the post-hypothyroid phase, and one patient underwent total thyroidectomy during the euthyroid phase of PT. Only four patients require beta-blocker therapy. All patients with KI-induced PT except 1 displayed GD remission during a mean observation period of 23.3 months, and 1 patient had recurrence of GD after PT. Conclusion We encountered 11 GD patients who developed PT during treatment with KI, which was initiated after ATD had been discontinued due to side effects.

A Case of Painless Thyroiditis Patient whom Recovery of Wholeness was Urged as an Opportunity to Drug Overdose of Thyroid Hormone

A Case of Painless Thyroiditis Patient whom Recovery of Wholeness was Urged as an Opportunity to Drug Overdose of Thyroid Hormone

Painless thyroiditis in a dupilumab-treated patient.

SummaryDupilumab an inhibitor of the interleukin (IL)-4R-alpha subunit is used for the treatment of allergic diseases. The patient was a 49-year-old man who received dupilumab for the treatment of severe atopic dermatitis. He presented hyperthyroidism with elevated thyroglobulin and anti-thyroid antibody negativity at 4 months after the initiation of therapy. On scintigraphy, the thyroid radioiodine uptake was low. Ultrasonography showed a diffuse hypoechoic area in the thyroid gland. A pathological study revealed lymphocytic infiltration. The administration of dupilumab was continued because of his atopic dermatitis that showed an excellent response. The patient`s hyperthyroidism changed to hypothyroidism 3 weeks later. Six months later his thyroid function normalized without any treatment. We herein describe the case of a patient with atopic dermatitis who developed painless thyroiditis under treatment with dupilumab. To the best of our knowledge, this is the first report of this event in the literature.Learning points:Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has been shown to be effective in the treatment atopic dermatitis and asthma with eosinophilia.Painless thyroiditis is characterized by transient hyperthyroidism and hypothyroidism and recovery without anti-thyroid treatment.This is the first report of painless thyroiditis as an adverse effect of dupilumab, although conjunctivitis and nasopharyngitis are the main adverse effects of dupilumab.

SAT-485 Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case Series

Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case SeriesIntroduction:Thyroid dysfunction is reported in 5 - 9.5 % of patients treated with Pembrolizumab, one of the PD-1 immune checkpoint inhibitors. However, the underlying mechanism of Pembrolizumab-induced thyroid disorders remains unclear.We present 3 clinical cases with Pembrolizumab-induced painless thyroiditis. They initially presented with thyrotoxicosis, but later converted to hypothyroidism. The onset of thyrotoxicosis after the treatment and time course of changing in thyroid function were varied among these cases. All three cases had normal thyroid function prior to the treatment.Case 1: 63-year-old M with bladder cancer, NSCLC and multiple brain metastases developed overt thyrotoxicosis with TSH 0.02 (0.34 - 4.82 mIU/mL) and Free T4 2.2 (0.8 - 1.5 ng/dL) at 108 days after the first cycle of Pembrolizumab. He had high TgAb (856) and TPO antibodies (196). In 14 days, he converted to hypothyroidism confirmed by TSH 14.6 and Free T4 0.8. Patient was started on Levothyroxine.Case 2: 69-year-old M with Stage IV NSCLC presented with thyrotoxicosis (TSH 0.01, Free T4 1.9) at days 41 after starting Pembrolizumab. TPO antibodies and TgAb were negative. During 51 days of follow up, he converted to hypothyroidism (TSH 8.89 and continued to trend up above 60). He eventually required levothyroxine therapy.Case 3: 57-year-old M with invasive verrucous squamous cell carcinoma of the perineum, urethra and prostate had normal TSH at baseline. Within 39 days after the first dose of pembrolizumab, TSH dropped to 0.013 and Total T4 increased to 14.8 (4.5 - 12.1 ug/dL), consistent with overt hyperthyroidism. In 108 days, patient developed hypothyroidism with Free T4 0.7.Discussion:All 3 cases we present did not have overt signs or symptoms of hyperthyroidism. Thyrotoxicosis spontaneously resolved without requiring steroid treatment. Studies suggest symptomatic treatment of beta blockers in cases of tachycardia, otherwise steroid use is not routinely recommended in PD1-induced thyroiditis.One cohort study analyzed the dynamic course of thyroid functions in patients receiving Pembrolizumab. Among the patients who developed thyrotoxicosis while on PD-1 inhibitor therapy, median onset time was 47 days (14–447 days). The median time for transition from thyrotoxicosis to hypothyroidism was 42 days (21–169 days).Conclusion:Our case series highlight the variations in the time course and nature of the Pembrolizumab-induced thyroiditis. Clinicians should be aware of the relatively short period of fluctuations of thyroid functions in patients treated with PD-1 inhibitors.

SAT-416 Novel Autoantibodies for Thyroid-Specific Transcriptional Factors in Patients with Immune-Related Adverse Events Involving the Thyroid Gland

Background: Immune-related adverse events by immune checkpoint inhibitors often involve several endocrine-related organs. PD-1 pathway blockade therapy by anti-PD-1 antibodies including nivolumab frequently causes thyroid dysfunction (thyroid irAE). Thyroid irAE seems to be distinctive compared to conventional painless thyroiditis in terms of a clinical course: transient thyrotoxicosis and subsequent persistent hypothyroidism [1]. Our retrospective cohort study regarding nivolumab provided several suggestions [2]. The thyroid irAE (+) group had a longer median overall survival than the thyroid irAE (−) group in patients with lung cancer, but this observation was not seen in patients with malignant melanoma: In addition, 5 of 17 patients tested at the point of thyroid dysfunction development were double negative for TPOAbs and TgAbs, known thyroid autoantibodies. From these findings, we set a hypothesis that antibodies for unknown antigens mediate prognostic effects of thyroid irAEs if tumor tissues express the same antigens. Methods: We performed co-immunoprecipitation using Protein G beads, sera of three patients with thyroid irAEs, and lysates of HEK293T cells overexpressing candidate proteins tagged with FLAG and HiBit (NKX2-1, PAX8, FOXE1, and HHEX). The pellets were analyzed by western blot. Results: FOXE1 bands were augmented in patient 1 with lung cancer, a PAX8 band in patient 2 with malignant melanoma, and bands of FOXE1, PAX8, and HHEX in patient 3 with renal cell carcinoma, compared to a control sample of a normal subject. We performed subcutaneous injections of purified IgG fraction from the serum of patient 3 to C57BL/6 mice every 2 weeks. The mice were sacrificed after 4 weeks, but no significant changes were observed in their thyroid glands and thyroid function. Conclusions: We identified novel autoantibodies for FOXE1, PAX8, and HHEX, thyroid-specific transcriptional factors. In our experiments, the pathogenicity of antibodies were not suggested. Considering our previous observation that the thyroid gland expresses both PD-L1 and PD-L2, ligands of PD-1 receptor [1], PD-1 pathway blockade may particularly disrupt immune tolerance of the thyroid gland, resulting in autoantibody production. Because thyroid irAEs have been revealed to be a prognostic factor, these novel autoantibodies are candidate biomarkers for PD-1 pathway blockade therapy.

Abstract #805894: All that Lithium Can Do! - A Rare Case of Painless Thyroiditis and Hyperthyroidism in Subclinical Hypothyroidism

Abstract #805894: All that Lithium Can Do! - A Rare Case of Painless Thyroiditis and Hyperthyroidism in Subclinical Hypothyroidism

Thyrotropin Receptor Antibody Immunoassays May Not Be Reliable in Confirming Diagnosis of Painless Thyroiditis

Scintigraphy using 99mTc-pertechnetate (TS) is the diagnostic test to differentiate thyroiditis following Graves' disease (GD) from painless thyroiditis (PT). However, TS may be contraindicated or unavailable. We compared the diagnostic effectiveness of two TSH receptor antibody (TRAb) immunoassays in untreated PT, already confirmed by qualitative and quantitative(99m) Tc-pertechnetate thyroid uptake (TCTU). TRAb assay and TS were performed in suspected PT patients. All 67 subjects (27 males) with confirmed diagnosis of PT based on qualitative (subjective) low uptake and quantitative uptake below 0.4% (Normal TcTU: 0.4-4%). During the period of study, we used two 2nd generation TRAb assays. Mean age, TSH, free T4 and TcTU were 40.5± 12.7 years, 0.066±0.089 mIU/L, 2.46±2.18 ng/mL and 0.188±0.0503% respectively. Fifteen (22.39%) of our PT patients were TRAb positive. Sensitivity, specificity, accuracy, PPV and NPV of TRAb in predicting thyroiditis were 81%, 75%, 78.2%, 83.6% and 74.4% in Assay 1. The same parameters were 74%, 64%, 71.2%, 76.8% and 62.7% respectively in TRAb Assay 2. However, ROC curve did not reveal any difference between the two assays. Negative TRAb value does not reliably distinguish PT from mild GD, in situations where TS is contraindicated or unavailable.

Allopurinol-induced hypersensitivity syndrome followed by painless thyroiditis in a patient with asymptomatic hyperuricemia.

Allopurinol-induced hypersensitivity syndrome followed by painless thyroiditis in a patient with asymptomatic hyperuricemia.

Painless destructive thyroiditis in a patient with resistance to thyroid hormone: a case report

BackgroundResistance to thyroid hormone (RTH) usually features a syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) without suppression of the typical high thyroid hormone levels. However, some patients with RTH show thyroid-stimulating hormone (TSH) suppression due to thyrotoxicosis. We report a case of painless thyroiditis in a patient with RTH that was misdiagnosed as Graves’ disease because of TSH-suppressed thyrotoxicosis.Case presentationA sixteen-year-old boy consulted a local general physician for fatigue. He had a goiter, and biochemical analysis showed TSH < 0.1 μIU/mL, free triiodothyronine (FT3) of 2.70 pg/mL, and free thyroxine (FT4) of 3.6 ng/dL. He was diagnosed with Graves’ disease and was treated with 20 mg thiamazole. One year later, he was referred to the department of endocrinology because of SITSH. He was finally diagnosed with RTH due to the finding of a heterozygous missense mutation (methionine 334 threonine) in the thyroid hormone receptor β gene. Three years after cessation of thiamazole, his hyperthyroxinemia showed marked exacerbation with TSH suppression. We diagnosed him with painless destructive thyroiditis because of low technetium-99 m (Tc-99 m) uptake in the thyroid. Extreme hyperthyroxinemia was ameliorated, with a return to the usual SITSH levels, within 1 month without any treatment.ConclusionThe present case demonstrates that diagnosing RTH is difficult when patients show hyperthyroxinemia with complete suppression of TSH to undetectable levels, and the data lead to misdiagnosis of RTH as Graves’ disease. The initial diagnosis is important, and Tc-99 m scintigraphy is useful for the differential diagnosis of thyrotoxicosis accompanying RTH.