Is Hashimoto thyroiditis associated with increasing risk of thyroid malignancies? A systematic review and meta-analysis

Background and purpose Hashimoto thyroiditis (HT) is the most common inflammatory autoimmune thyroid disease and also the most common cause of hypothyroidism in developed countries. There is evidence of the role of HT in developing thyroid cancers (TCs). This study investigated the association between HT and different types of TCs. Methods Results of a comprehensive search in three major databases, as well as hand searching, were screened in title/abstract and full-text stages and the relevant data were extracted from the studies that met the inclusion criteria. Risk of bias (RoB) was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and the meta-analysis was conducted with Comprehensive Meta-Analysis software. Results Out of 4785 records, 50 studies were included in the systematic review, and 27 of them met the criteria for quantitative synthesis. The results indicated a significant role for HT in developing papillary TC (OR: 1.65; 95% CI: 1.04 to 2.61), medullary TC (OR: 2.70; 95% CI: 1.20 to 6.07) and lymphoma (OR:12.92; 95% CI: 2.15 to 77.63); but not anaplastic TC (OR: 1.92; 95% CI: 0.29 to 1.90) and follicular TC (OR: 0.73; 95% CI: 0.41 to 1.27). Also, this study found a significant association between HT and thyroid malignancies (OR: 1.36; 95% CI: 1.05 to 1.77). Conclusion Although we found a significant association between HT and some types of TCs, High RoB studies, high level of heterogeneity, and the limited number of well-designed prospective studies, suggested the need for more studies to reach more reliable evidence.

Autoantibody Release in Children after Corona Virus mRNA Vaccination: A Risk Factor of Multisystem Inflammatory Syndrome?

Multisystem inflammatory syndrome (MIS) is a new systemic inflammatory acute onset disease that mainly affects children (MIS-C) and, at a lesser frequency, adults (MIS-A); it typically occurs 3–6 weeks after acute SARS-CoV infection. It has been postulated and shown in adults that MIS may occur after SARS-CoV-2 vaccination (MIS-V). Our current case is one of the first published cases with a multisystem inflammatory syndrome in an 18-year-old adolescent after the SARS-CoV-2 vaccine from Pfizer/BionTech (BNT162b2), who fulfills the published level 1 criteria for a definitive disease: age < 21 years, fever > 3 consecutive days, pericardial effusion, elevated CRP/NT-BNP/Troponin T/D-dimeres, cardiac involvement, and positive SARS-CoV-2 antibodies. The disease starts 10 weeks after the second vaccination, with a fever (up to 40 °C) and was treated with amoxicillin for suspected pneumonia. The SARS CoV-2-PCR and several antigen tests were negative. With an ongoing fever, he was hospitalized 14 days later. A pericardial effusion (10 mm) was diagnosed by echocardiography. The C-reactive protein (174 mg/L), NT-BNP (280 pg/mL), and Troponin T (28 pg/mL) values were elevated. Due to highly elevated D-dimeres (>35,000 μg/L), a pulmonary embolism was excluded by thoracal computer tomography. If the boy did not improve with intravenous antibiotics, he was treated with intravenous immunoglobulins; however, the therapy was discontinued after 230 mg/kg if he developed high fever and hypotension. A further specialized clinic treated him with colchicine and ibuprofen. The MIS-V was discovered late, 4 months after the onset of the disease. As recently shown in four children with MIS-C after SARS-CoV-2 infection and a girl with Hashimoto thyroiditis after BNT162b2 vaccination, we found elevated functional autoantibodies against G-protein-coupled receptors that may be important for pathophysiology but are not conclusive for the diagnosis of MIS-C. Conclusion: We are aware that a misattribution of MIS-V as a severe complication of coronavirus vaccination can lead to increased vaccine hesitancy and blunt the global COVID-19 vaccination drive. However, the pediatric population is at a higher risk for MIS-C and a very low risk for COVID-19 mortality. The publication of such cases is very important to make doctors aware of this complication of the vaccination, so that therapy with intravenous immunoglobulins can be initiated at an early stage.

Gluten intolerance and hashimoto thyroiditis: an integrated review

The advent of agriculture about 10,000 years ago enabled the massive and widespread use of grains containing gluten in food. Thus, it represented an evolutionary challenge that has not yet been overcome and created the conditions for the development of diseases related to exposure to gluten in humans. The so-called hypersensitivity involves any abnormal reaction resulting from eating a particular food. We are now looking at another interesting phenomenon that is causing great confusion among healthcare professionals. The number of individuals embracing a gluten-free diet appears far greater than the predicted number of celiac patients, fueling a global gluten-free product market approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to gluten intake have emerged as health concerns. Hashimoto's Thyroiditis is an autoimmune disease and the most common cause of hypothyroidism in our environment. It occurs with high familial aggregation and there seems to be a clear genetic predisposition, with an apparent autosomal dominant inheritance of autoantibodies in affected individuals. Food intolerance and allergies and intestinal permeability can accompany hypothyroidism. Food (food intolerance and allergies), bacteria, viruses, chemicals, excess bacterial growth in the intestine, intestinal permeability, and contaminants are the main culprits for the autoimmune thyroid disease – Hashimoto's thyroiditis.

Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution

The tumor microenvironment heterogeneity of papillary thyroid cancer (PTC) is poorly characterized. The relationship between PTC and Hashimoto thyroiditis (HT) is also in doubt. Here, we used single-cell RNA sequencing to map the transcriptome landscape of PTC from eight PTC patients, of which three were concurrent with HT. Predicted copy number variation in epithelial cells and mesenchymal cells revealed the distinct molecular signatures of carcinoma cells. Carcinoma cells demonstrated intertumoral heterogeneity based on BRAF V600E mutation or lymph node metastasis, and some altered genes were identified to be correlated with disease-free survival in The Cancer Genome Atlas datasets. In addition, transcription factor regulons of follicular epithelial cells unveil the different transcription activation state in PTC patients with or without concurrent HT. The immune cells in tumors exhibited distinct transcriptional states, and the presence of tumor-infiltrating B lymphocytes was predominantly linked to concurrent HT origin. Trajectory analysis of B cells and plasma cells suggested their migration potential from HT adjacent tissues to tumor tissues. Furthermore, we revealed diverse ligand–receptor pairs between non-immune cells, infiltrating myeloid cells, and lymphocytes. Our results provided a single-cell landscape of human PTC. These data would deepen the understanding of PTC, as well as the immunological link between PTC and HT.

Episodic Hemiparesis, Cognitive Decline, and Seizures in a Woman With Pernicious Anemia

A 46-year-old woman with a history of pernicious anemia, sought care for intermittent episodes of weakness in her right upper extremity and speech difficulties followed by a headache. It was initially thought that she had migraine headaches. Blood tests showed increased thyrotropin and low free thyroxine levels, and she was diagnosed with Hashimoto thyroiditis. She initiated treatment with levothyroxine. One month later, the patient had a confusional episode and over the course of the following 2 months, the cognitive difficulties progressed. She was brought to the emergency department after a generalized tonic-clonic seizure. On examination, she was profoundly encephalopathic. Formal bedside cognitive testing could not be obtained. Findings of magnetic resonance imaging of the brain were normal. Electroencephalography revealed diffuse slowing. Cerebrospinal fluid analysis showed increased protein concentration and lymphocytic pleocytosis. Thyroid peroxidase antibody value was markedly increased. Thyroglobulin antibody value was also increased. Consistent with her history of pernicious anemia, she was positive for gastric parietal cell antibodies. The clinical presentation was compatible with steroid-responsive encephalopathy associated with autoimmune thyroiditis, also known as Hashimoto encephalopathy. The patient started levetiracetam therapy and had no further seizures. She received intravenous methylprednisolone. At the completion of treatment, her confusion rapidly and substantially improved. She was discharged home on oral prednisone. She also started pantoprazole, calcium, and vitamin D supplementation and Pneumocystis jirovecii prophylaxis. For long-term immunotherapy, she initiated methotrexate. Three months later, the patient and her family reported 90% improvement in her cognitive functioning and resolution of the episodes of hemiparesis. The patient continued tapering prednisone. It was recommended that she continue methotrexate for 5 years before discontinuing. Steroid-responsive encephalopathy associated with autoimmune thyroiditis, also known as Hashimoto encephalopathy, was initially described as strokelike episodes and subacute encephalopathy months after the onset of autoimmune (Hashimoto) thyroiditis.

Are Nutritional Patterns among Polish Hashimoto Thyroiditis Patients Differentiated Internally and Related to Ailments and Other Diseases?

There is not any diet recommended for Hashimoto’s disease, despite that those patients are often undernourished. Because of the high heterogeneity of Hashimoto’s patients, insight into dietary patterns might shed some light on the patient-tailored dietary approach, thus improving their treatment and helping to identify patients with the highest probability of particular nutritional deficiencies. The aim of this study was to identify Hashimoto’s patients’ dietary patterns and their characterization based on both socio-demographic variables and dietary self-assessment. We collected data online from patients with Hashimoto’s disease. The questionnaire formula used in the study was developed based on a validated food frequency questionnaire KomPAN®. K-means pattern analyses were used to characterize patients into patterns based on the frequency of particular types of foods consumption and socio-demographic factors. Four patterns were identified. We labeled them as ‘Convenient’, ‘Non-meat’, ‘Pro-healthy’, and ‘Carnivores’ with participants proportions at approximately one-fourth per each pattern. The patients were mainly of the female gender (94.08%), with a female: male ratio of 15.9. Hashimoto’s patients differed in their food product choices, food choice motives, dieting experience, nutritional knowledge, smoking habits, food allergies and intolerances, and lipid disorders, and thus represent different eating patterns. However, these patterns were not determined by comorbidities or the majority of ailments.

Co-occurrence of Relapsing Polychondoritis and Autoimmune Thyroid Diseases

Background: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilageous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves’ disease (GD) and Hashimoto thyroiditis (HT). However there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed clinical and genetic profiles of patients in whom these diseases co-occur.Methods: We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1 and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD.Results: The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p=2.44×10-7, binomial test). RP patients with GD tended to have nasal involvement (p=0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p=0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP.Conclusions: Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 may characterize the subset of RP patients with GD, which may guide attempts to characterize distinct subtype of RP for precision medicine.

An aggressive case of Warthin-like variant of papillary thyroid carcinoma (PTC)

Introduction/Objective Warthin-like variant of PTC is a rare subtype of PTC, characterized by papillary growth lined with oncocytic neoplastic cells and lymphocytic rich stroma in the stalks of the papillae. It is frequently associated with Hashimoto thyroiditis and has good prognosis due to lower risk of metastasis. An association with BRAF V600E mutation has been reported. Here we report an aggressive case of Warthin-like variant of PTC. Methods/Case Report A 33-year-old Hispanic female presented with a progressively expanding neck mass, difficulty swallowing, voice hoarseness, and neck pain. Ultrasound showed a 3.8 cm left thyroid nodule which on biopsy was positive for PTC. Laboratory tests were positive for anti-peroxidase and anti-thyroglobulin antibodies. A total thyroidectomy was performed. Grossly, the left thyroid lobe nodule was well-circumscribed, unencapsulated, and firm with solid homogenous gray-tan cut surface. Microscopically, the nodule consisted of large eosinophilic cells demonstrating characteristic PTC nuclear features, arranged in papillary structures with the cores packed with prominent lymphoplasmacytic infiltrate consistent with Warthin-like variant of PTC (figure). Separate sub-centimeter foci of PTC with similar features were identified in a background of chronic lymphocytic thyroiditis. Central and left neck dissection showed extensive lymph node metastasis which had features similar to the primary tumor but with less pronounced lymphoplasmacytic cores. The patient is currently 6-month post operation and is receiving iodine ablative therapy. Results (if a Case Study enter NA) NA Conclusion Molecular analysis of the tumor may aid in identifying molecular aberrations responsible for the aggressive nature in this case and potentially guide treatment.