Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.

BACKGROUND: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. METHODS: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. FINDINGS: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. INTERPRETATION: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. FUNDING: Research Foundation Flanders.

A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer.

Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 µg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.

Volume reduction rate of radiofrequency ablation in ≤ 2 cm Bethesda IV thyroid nodules.

OBJECTIVE: This prospective observational study aimed to evaluate the efficacy of radiofrequency ablation (RFA) in treating ≤ 2 cm thyroid nodules with Bethesda IV cytology and C-TIRADS 4A categorization. Additionally, the factors influencing the completed absorption of ablation (CAA) were examined. METHODS: A total of 62 cases with 62 nodules underwent ultrasound-guided RFA and were included in the study. The volume reduction rate (VRR), CAA, and incomplete absorption of ablation (IAA) were assessed at the 1st, 3rd, 6th, and subsequent 6-month follow-ups. Clinical and ultrasound features were compared between the CAA and IAA groups at the 12th month follow-up. RESULTS: The average VRR at the 1st, 3rd, 6th, 12th month, and last follow-up were -88.6%, 16.0%, 59.7%, 82.0%, and 98.2%, respectively. More than half of the nodules achieved a 90% VRR after 1 year of RFA, with 88.7% demonstrating CAA at the end of the study (follow-up duration of 14 to 63 months). Nodules with grade 3 vascularity and those associated with chronic thyroiditis showed delayed CAA at the 12th month follow-up (p = 0.036 and 0.003, respectively). CONCLUSION: RFA is an effective technique for treating ≤ 2 cm thyroid nodules with Bethesda IV cytology and C-TIRADS 4A categorization. Nodules with grade 3 blood supply and patients with chronic thyroiditis exhibited an impact on the completed absorption following RFA. CLINICAL RELEVANCE STATEMENT: Our study has shown that radiofrequency ablation is an effective treatment for ≤ 2 cm thyroid nodules classified as Bethesda IV cytology. However, we identified that high vascularity of the nodule and chronic thyroiditis are adverse factors affecting the completed absorption of the ablation. KEY POINTS: •Radiofrequency ablation (RFA) is an effective technique for treatment of ≤ 2 cm Bethesda IV category thyroid nodules. •Higher blood supply and chronic thyroiditis influence the completed absorption after RFA.

Risk of autoimmune diseases after post-traumatic stress disorder: a nationwide cohort study.

This longitudinal study aimed to investigate the risk of subsequent autoimmune disease in patients with post-traumatic stress disorder (PTSD) in Asian population. Between 2002 and 2009, we enrolled 5273 patients with PTSD and 1:4 matched controls from the National Health Insurance Database of Taiwan, and followed up the patients until December 31, 2011, or death. The investigated autoimmune diseases included thyroiditis, lupus, rheumatic arthritis, inflammatory bowel disease, Sjogren's syndrome, dermatomyositis, and polymyositis. The Cox regression model was used to estimate the risk of developing autoimmune diseases, with adjustment for demographics and psychiatric and medical comorbidities. Furthermore, we examined the psychiatric clinics utility of patients with PTSD indicating the severity of PTSD in association with autoimmune diseases. After adjusting for confounders, patients with PTSD had a 2.26-fold higher risk of developing any autoimmune diseases (reported as hazard ratios with 95% confidence intervals: 1.82-2.80) than the controls. For specific autoimmune diseases, patients with PTSD had a 2.70-fold higher risk (1.98-3.68) of thyroiditis, a 2.95-fold higher risk (1.20-7.30) of lupus, and a 6.32-fold higher risk (3.44-11.60) of Sjogren's syndrome. Moreover, the PTSD severity was associated with the risk of autoimmune diseases in a dose-dependent manner. The patient with the highest psychiatric clinics utility was associated with an 8.23-fold higher risk (6.21-10.90) of any autoimmune diseases than the controls. Patients with PTSD had an increased risk of autoimmune diseases, and such risk was associated with the severity of PTSD in a dose-dependent manner. However, the present study did not provide a direct effect between PTSD and autoimmune diseases, but rather an association. Further studies are warranted to examine the underlying pathophysiological mechanisms.

Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.

OBJECTIVE: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19. METHODS: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase. RESULTS: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses. CONCLUSION: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

PURPOSE: In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. METHODS: We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. RESULTS: There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. CONCLUSION: However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

Advancements in diagnosing IgG4-related disease of the head and neck: Navigating diagnostic pitfalls.

IgG4-related disease (IgG4-RD) is an immune-mediated condition affecting nearly any organ. This review focuses on the nuances of diagnosing IgG4-RD affecting the head and neck. Salivary gland involvement, especially of the submandibular glands, often permits a definitive diagnosis on biopsy. However, elevated IgG4+ plasma cells are nonspecific and can be seen in chronic sialadenitis, lymphoma, and other mimics. Careful correlation of clinical and pathological findings is essential. Given the significant overlap with chronic sinusitis, IgG4-RD of the sinonasal region is difficult to diagnose histologically. Laryngeal and pharyngeal involvement appears rare as an isolated finding of IgG4-RD. Mastoid disease is uncommon and remains a diagnosis of exclusion. Thyroid manifestations pose challenges given unclear diagnostic criteria - Riedel's thyroiditis likely represents IgG4-RD, but the fibrosing variant of Hashimoto's thyroiditis as a form of the so-called 'IgG4-related thyroiditis' requires better characterisation. Eosinophilic angiocentric fibrosis, despite histologic similarities, only partially overlaps with IgG4-RD. This review aims to guide diagnosing IgG4-RD in the head and neck through a systematic, organ-focused discussion of the clinical context, the utility of immunostaining, histological mimics, and controversial issues that pose diagnostic pitfalls. Increased awareness of the nuances and difficulties diagnosing IgG4-RD affecting the head and neck will improve recognition of this protean disease.

Langerhans cell histiocytosis of the thyroid mimicking thyroiditis in a boy: a case report and literature review.

BACKGROUND: Langerhans cell histiocytosis affecting the thyroid commonly presents with nonspecific clinical and radiological manifestations. Thyroid Langerhans cell histiocytosis is typically characterized by non-enhancing hypodense lesions with an enlarged thyroid on computed tomography medical images. Thyroid involvement in LCH is uncommon and typically encountered in adults, as is salivary gland involvement. Therefore, we present a unique pediatric case featuring simultaneous salivary and thyroid involvement in LCH. CASE PRESENTATION: A 3-year-old boy with complaints of an anterior neck mass persisting for 1 to 2 months, accompanied by mild pain, dysphagia, and hoarseness. A physical examination revealed a 2.5 cm firm and tender mass in the left anterior neck. Laboratory examinations revealed normal thyroid function test levels. Ultrasonography revealed multiple heterogeneous hypoechoic nodules with unclear and irregular margins in both lobes of the thyroid. Contrast-enhanced neck computed tomography revealed an enlarged thyroid gland and bilateral submandibular glands with non-enhancing hypointense nodular lesions, and multiple confluent thin-walled small (< 1.5 cm) cysts scattered bilaterally in the lungs. Subsequently, a left thyroid excisional biopsy was performed, leading to a histopathological diagnosis of LCH. Immunohistochemical analysis of the specimen demonstrated diffuse positivity for S-100, CD1a, and Langerin and focal positivity for CD68. The patient received standard therapy with vinblastine and steroid, and showed disease regression during regular follow-up of neck ultrasonography. CONCLUSIONS: Involvement of the thyroid and submandibular gland as initial diagnosis of Langerhans cell histiocytosis is extremely rare. It is important to investigate the involvement of affected systems. A comprehensive survey and biopsy are required to establish a definitive diagnosis.

Hashimoto's Thyroiditis Negatively Influences Intracytoplasmic Sperm Injection Outcome in Euthyroid Women on T4 Substitution Therapy: A Retrospective Study.

OBJECTIVE: The objective of this study was to analyze the impact of thyroid autoimmunity (TAI) on reproductive outcome parameters of intracytoplasmic sperm injection (ICSI) cycles as compared to TAI-negative ICSI cycles. DESIGN: In this single in vitro fertilization (IVF) center retrospective study, 86 infertile women with elevated thyroid peroxidase or TGAb levels, but euthyroid after thyroxine replacement (study group), were compared to 69 female patients with no thyroid abnormalities (controls). Following ICSI treatment fertilization rate (FR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR) were analyzed. MATERIALS, SETTING, METHODS: All subjects with various infertility factors were treated with ICSI in university-based IVF center. Patients in the study group received thyroxine replacement and were euthyroid at IVF treatment. Before the IVF cycles, endocrinological parameters were uniformly assessed: thyroid function and antibodies, reproductive hormones (anti-Müllerian hormone [AMH], follicular stimulating hormone [FSH], luteinizing hormone, E2, PRL, testosterone, DHEAS, 17-OHP, AD) and OGTT (0-60-120 min glucose and insulin). Following descriptive comparison of laboratory parameters, age-adjusted analyses of FR, CPR, MR, and LBR were performed. RESULTS: TAI-positive women were older (mean age 35.31 ± 4.95 vs. 32.15 ± 4.87 years; p = 0.002), had higher FSH (8.4 ± 3.4 vs. 7.4 ± 2.32 U/L; p = 0.024), higher E2 (53.94 ± 47.61 vs. 42.93 ± 18.92 pg/mL; p = 0.025) levels, while AMH (2.88 ± 2.62 vs. 3.61 ± 1.69 ng/mL; p = 0.0002) was lower. There were no differences in TSH levels (1.64 ± 0.96 vs. 1.66 ± 0.65 µIU/mL; p = 0.652) between the two groups. FT3 (2.63 ± 0.58 vs. 2.98 ± 0.55 pg/mL; p = 0.002) was lower and FT4 (1.3 ± 0.29 vs. 1.13 ± 0.21 ng/dL; p = 0.0002) was higher in the TAI-positive group, reflecting clinically irrelevant differences. Egg cell counts (6 ± 3.8 vs. 7.5 ± 3.95; p = 0.015) were lower in TAI and remained so following age adjustment. Although the overall ICSI FR did not differ (62.9% vs. 69.1%, p = 0.12), it was lower for patients under 35 with TAI showing decreasing differences in line with age. The CPR (36.04% vs. 69.56%; p < 0.001) and LBR (23.25% vs. 60.86%; p < 0.001) were lower, the MR (35.48% vs. 12.5%; p = 0.024) was higher in the TAI group, and these differences remained after age adjustment. LIMITATIONS: Since the higher age of the study group may interfere with the effect of TAI, age adjustment calculations were necessary to perform to eliminate this confounding factor. CONCLUSION: Despite optimal thyroid supplementation in clinical or subclinical hypothyroidism, the presence of TAI negatively influences CPR and is connected to a higher MR, thus resulting in a lower LBR after ICSI. Decreased FR with ICSI in TAI patients may also contribute to poorer outcomes, especially in younger women.

ADVANCED DIAGNOSTIC IMAGING AND PATHOLOGIC FINDINGS OF THYROID LESIONS IN TWO SHORT-BEAKED ECHIDNAS (TACHYGLOSSUS ACULEATUS).

Two zoo-maintained short-beaked echidnas (Tachyglossus aculeatus) had long histories of intermittent anorexia and lethargy. Case 1 presented with a recurrence of these signs after transfer to another facility and died shortly after arrival. A focal area of hyperattenuation within the paratracheal tissue of the cranial mediastinum was noted antemortem on CT. Postmortem, this corresponded with severe thyroid follicular hyperplasia with lymphoplasmacytic thyroiditis. Additional findings included a systemic fungal infection without an inflammatory response, suggesting underlying factors such as torpor or immunosuppression. In Case 2, an intrathoracic mass was identified during a preshipment examination. CT confirmed a contrast-enhanced mass compressing the cranial vena cava and right atrium, and the animal was euthanized. The mass was diagnosed histologically as thyroid adenocarcinoma. These cases report thyroiditis and thyroid adenocarcinoma in echidna and describe the use of IV contrast and CT as a diagnostic aid in this species.

A novel hybrid model to predict concomitant diseases for Hashimoto's thyroiditis.

Hashimoto's thyroiditis is an autoimmune disorder characterized by the destruction of thyroid cells through immune-mediated mechanisms involving cells and antibodies. The condition can trigger disturbances in metabolism, leading to the development of other autoimmune diseases, known as concomitant diseases. Multiple concomitant diseases may coexist in a single individual, making it challenging to diagnose and manage them effectively. This study aims to propose a novel hybrid algorithm that classifies concomitant diseases associated with Hashimoto's thyroiditis based on sequences. The approach involves building distinct prediction models for each class and using the output of one model as input for the subsequent one, resulting in a dynamic decision-making process. Genes associated with concomitant diseases were collected alongside those related to Hashimoto's thyroiditis, and their sequences were obtained from the NCBI site in fasta format. The hybrid algorithm was evaluated against common machine learning algorithms and their various combinations. The experimental results demonstrate that the proposed hybrid model outperforms existing classification methods in terms of performance metrics. The significance of this study lies in its two distinctive aspects. Firstly, it presents a new benchmarking dataset that has not been previously developed in this field, using diverse methods. Secondly, it proposes a more effective and efficient solution that accounts for the dynamic nature of the dataset. The hybrid approach holds promise in investigating the genetic heterogeneity of complex diseases such as Hashimoto's thyroiditis and identifying new autoimmune disease genes. Additionally, the results of this study may aid in the development of genetic screening tools and laboratory experiments targeting Hashimoto's thyroiditis genetic risk factors. New software, models, and techniques for computing, including systems biology, machine learning, and artificial intelligence, are used in our study.

miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT. METHODS: Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT. RESULTS: We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1. CONCLUSIONS: Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT.

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-1ß, 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.

Comprehensive analysis of hub biomarkers associated with immune and oxidative stress in Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.

Analysis of the effect of hashimoto's thyroiditis and insulin resistance on ovarian volume in patients with polycystic ovary syndrome.

OBJECTIVE: In this study, patients were divided into two groups. Patients with polycystic ovary syndrome (PCOS) and patients with polycystic ovary syndrome + Hashimoto's Thyroid (PCOS + HT). The effect of insulin resistance on ovarian volume in patients divided into two groups and the change in ovarian volume with the addition of HT to PCOS will be investigated. MATERIAL AND METHODS: 46 PCOS patients and 46 PCOS patients diagnosed with HT were included in this study. A detailed medical history was taken from all participants. Polycystic ovary image was evaluated as below or above 10 ml and antral follicles were counted by transvaginal ultrasound. Insulin resistance of the patients was evaluated according to the fasting insulin (HOMA) index. RESULTS: Insulin resistance was found to be associated with fasting insulin, HOMA index, body mass index and right ovarian volume in patients diagnosed with PCOS. Among the patients diagnosed with PCOS + HT, insulin resistance was found to be significantly correlated with fasting insulin, HOMA index, (BMI), (SHBG) and left ovarian volume. An increase in right ovarian volume was found in 37.5% of patients with PCOS without insulin resistance and in 76.3% of patients with insulin resistance. An increase in left ovarian volume was found in 35.7% of patients without insulin resistance diagnosed with PCOS + HT and in 68.8% of patients with insulin resistance. CONCLUSIONS: This study shows that ovarian volume should be evaluated in every PCOS patient in order to predict insulin resistance, which causes long-term metabolic diseases, and that all PCOS patients with increased ovarian volume should be investigated for insulin resistance. In addition, it has been observed that insulin resistance affects left ovarian volume in patients with PCOS + HT, whereas insulin resistance affects the volume of the right ovary more in patients with PCOS. At least one ovary has been found to be affected by long-term metabolic diseases. While there was a greater increase in ovarian volume with the addition of insulin resistance, no significant change was observed in the number of patients with increased ovarian volume (PCOS-58, PCOS + HT-57) with the addition of HT finding.

Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Painless thyroiditis mimicking relapse of hyperthyroidism during or after potassium iodide or thionamide therapy for Graves' disease resulting in remission.

The diagnosis of painless thyroiditis (PT) during antithyroid drug (ATD) treatment of Graves' disease (GD) is difficult. We evaluated the thyroidal radioactive iodine uptake (RAIU) in 100 patients with relapsed thyrotoxicosis during or after careful ATD treatment. The RAIU was <5%/5 h in 35 patients (35%) (Group A - PT), 5%-15%/5 h in 6 patients (6%) (Group B - indefinite) and >15%/5 h in 59 patients (59%) (Group C - relapsed GD [rGD]). TSH receptor antibody (TBII) was positive in 4 (11.4%), 3 (50.0%) and 39 (only 66.1%) patients in Groups A, B and C, respectively. In Group A, the serum fT4 level spontaneously normalized after 35 (26-56) days, sometimes followed by transient hypothyroidism, confirming the diagnosis of PT. Nineteen (54.3%) had been treated with potassium iodide, and PT frequently occurred ironically when the ATD dosage was reduced. PT repeatedly occurred in nine patients. All went into remission smoothly or developed hypothyroidism, except one patient with strongly positive TBII who developed rGD after the resolution of PT (PT on GD). In 10 (50%) of 20 patients with negative TBII despite rGD in Group C, TBII became positive afterwards. In conclusion, it is important to recognize that PT can occur in the clinical course of GD, resulting in frequent remission despite relapse of PT. The thyroid function reflects the balance between the stimulating TBII activity and the responsiveness of the thyroid tissue (sometimes unresponsive and other times autostimulated). The RAIU is still a valuable tool in cases of ambiguous thyrotoxicosis.

Atezolizumab induced new-onset type 1 diabetes mellitus.

INTRODUCTION: Immune checkpoint inhibitors (ICI) are novel therapeutic strategies in cancer treatment, promoting anti-tumor response by boosting cytotoxic T lymphocytes. Despite their high effectiveness, they can trigger the activation of diverse autoimmune diseases in genetically predisposed individuals. New-onset autoimmune diabetes mellitus type 1 (T1D) is an extremely unusual side effect, described in less than 1% of patients. CASE REPORT: Here we present a 44-year-old male diagnosed with non-surgical hepatocarcinoma, developing programmed death ligand-1 inhibitor-induced autoimmune endocrinopathies, presented as diabetic ketoacidosis and thyroiditis. After two cycles of atezolizumab and bevacizumab, he consulted the emergency department with abdominal pain and diabetes cardinal features (polyuria, polydipsia, vomiting). Blood tests demonstrated hyperglycemia >800 mg/dL, capillary ketonemia >3 mmol/L, metabolic acidosis (pH 7.24 with HCO3 14 mEq/L). Subsequent studies detected a low level of C-peptide, and positive glutamic acid decarboxylase and insulinoma-associated antigen-2 antibodies. Thyroid examination was compatible with thyroiditis, showing a high free thyroxine level (1.91 ng/dL) with low thyrotropin (TSH) (0.08 mIU/L) and negative anti-TSH receptor antibody. MANAGEMENT & OUTCOME: After reaching metabolic stabilization, treatment with Atezolizumab was restarted, with no further complications showing size stability in the computed tomography control. DISCUSSION: T1D related to ICI is a rare condition that presents as a life-threatening emergency and should be recognized and treated early. Blood glucose and glycated hemoglobin determinations should be performed at periodic visits for detection. There are genetic factors that predispose susceptible individuals, but there is no evidence of studies to be performed before the onset of ICI or preventive strategies.

Hyperthyroidism: A Review.

Importance: Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations: The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance: Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.