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Purpose: To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions. Methods: Cross sectional, single center study, involving all consecutive patients (N = 3015) who were submitted to thyroid surgery between 2001–2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed. Results: No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99–2.28) and certain (OR: 1.74, 95% CI: 1.09–2.78) thyroid autoimmunity (p = 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08–1.45, p = 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24–0.67, p < 0.001). The most frequent genetic alteration was BRAFV600E mutation, found in 56.3% of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAFV600E mutation was observed. Conclusions: Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression. [ABSTRACT FROM AUTHOR]

Context Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions. Objective This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD. Methods This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7719 ultrasonography images from 351 patients with GD and 2980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0_2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image preprocessing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform. Results The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0_2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99. Conclusion Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis. [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested a correlation between alopecia areata (AA) and thyroid dysfunction (TD). However, the causal relationship between AA and TD remains uncertain. The purpose of this study is to investigate the causal relationship between these two conditions. Understanding the potential causal relationship between AA and TD is valuable for elucidating the pathogenesis of AA and for designing innovative methods to prevent and treat AA and its related complications. Methods: All data for this two‐sample Mendelian randomization (MR) study were sourced from public databases. This study selected hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, and Graves' disease as exposure factors, with AA as the outcome variable. Data for hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, Graves' disease, and AA were obtained from related genome‐wide association studies (GWAS). Various MR analysis methods such as inverse variance weighted (IVW), MR‐Egger, and weighted median were utilized. Additionally, Cochrane's Q test was used to detect heterogeneity in MR results, and the MR‐Egger intercept test and MR pleiotropy residual sum and outlier (MR‐PRESSO) test were used to detect horizontal pleiotropy. A leave‐one‐out analysis was conducted to investigate the sensitivity of this association. Results: We found statistically significant genetic predictions of AA with hypothyroidism, Hashimoto's thyroiditis, and subacute thyroiditis (IVW OR = 1.4009815, 95% confidence interval [CI]: 1.1210399–1.750829; p = 0.003030698, OR = 1.396101, 95% CI: 1.030134–1.89208; p = 0.03144273, OR = 0.732702, 95% CI: 0.604812–0.887634; p = 0.001483368). Furthermore, tests for pleiotropy showed no evidence of pleiotropy, enhancing the credibility of the study results. Finally, the leave‐one‐out test demonstrated the stability and robustness of this association. Conclusion: This study provides new evidence of a potential genetic link between thyroid issues and AA. By employing the two‐sample MR method to eliminate confounding factors and reverse causation, unbiased results were obtained, confirming a causal relationship between hypothyroidism, Hashimoto's thyroiditis, subacute thyroiditis, and AA. This lays the foundation for further mechanistic studies and potential clinical applications. Future research should further explore the specific biological mechanisms between TD and the onset of AA. [ABSTRACT FROM AUTHOR]

Introduction: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare autoimmune disorder affecting the central nervous system, characterized by a spectrum of neurological and psychiatric symptoms. Aim: This case study aims to highlight the diagnostic challenges and the successful management of SREAT syndrome in a young woman with autoimmune thyroiditis. Case study: A 21-year-old woman with documented Hashimoto's thyroiditis and polycystic ovary syndrome was admitted to the Clinic of Neurology following a 5-minute tonic seizure and subsequent confusion state lasting several hours. Initial brain MRI showed no abnormalities, and EEG revealed generalized slowness. Comprehensive laboratory assessments, including a complete blood count, biochemical analysis, and electrolyte panels, all yielded normal results. Further investigation revealed a significantly elevated anti-thyroid peroxidase antibody (anti-TPO) titer exceeding 1000 IU/mL. The suspicion of SREAT syndrome was considered. Pulse therapy with methylprednisolone was associated with rapid recovery. The patient was discharged from the hospital with an oral corticosteroid tapering regimen. Results and discussion: The administration of pulse therapy with methylprednisolone resulted in a rapid and very good response in the patient, evidenced by the resolution of seizure activity and improvement in confusion. Laboratory investigations, particularly the markedly elevated anti-TPO titer, supported the diagnosis of SREAT syndrome. The subsequent management with an oral corticosteroid tapering regimen maintained the patient's clinical stability. Conclusions: This case highlights the importance of considering autoimmune encephalopathy in patients with a history of autoimmune thyroiditis presenting with neurological and psychiatric symptoms. Further research is warranted to better understand the underlying pathomechanisms. [ABSTRACT FROM AUTHOR]

A common immune-related adverse event (irAE) with immune checkpoint inhibitors (ICIs) is thyroid dysfunction (TD-irAEs). The clinical presentation can be varied, and its association with prognosis remains unclear. We investigated the characteristics of TD-irAEs and their association with clinical outcomes among cancer patients treated with ICIs in a real-life setting. Response to treatment was assessed using RECIST v1.1. We calculated the probability of recurrence and survival associated with TD-irAEs using multivariable-adjusted regression and Cox proportional hazards models. In this single-center retrospective analysis, we included 238 patients (72% male) with a median age of 69.5 years. Primary tumors were melanoma (23.1%), lung (60.5%), or urothelial cancer (16.4%), treated with atezolizumab (23.1%), pembrolizumab (44.5%), ipilimumab (0.4%), and/or nivolumab (25.6%). Seventy (29%) patients developed TD-irAEs in a median time of 69 days (41-181). The incidence of TD-irAEs with combination therapy was higher than with monotherapy (67% vs 6.3%, P = 0.011). TD-irAE patients showed a higher objective response rate (ORR) than those without TD-irAEs (60% vs 42.3%, P = 0.013) and longer overall survival (OS) 45 vs 16 months, P < 0.006. Patients who developed TD-irAEs had a relative reduction of 77% (OR 0.23, 95% CI 0.11-0.47) in the risk of progression and of 47% in the risk of mortality (HR 0.53, 95% CI 0.36-0.80), independent of age, sex, primary tumor, or ICI regimen. TD-irAEs occur in nearly 30% of our patients receiving ICIs. In our analysis, TD-irAEs appeared to be associated with higher ORR and longer OS and showed a reduction in the risk of progression and mortality. [ABSTRACT FROM AUTHOR]

Background: The rearranged during transfection (RET) proto-oncogene fusion is common in papillary thyroid cancer (PTC), varying across ethnic groups. However, comprehensive comparisons of RET fusion types are limited. This study aims to identify predominant RET fusions and analyze their clinicopathological characteristics in a cohort of Chinese thyroid cancer cases. Methods: This single-center retrospective cohort study analyzed thyroid cancer data, utilizing next-generation sequencing on formalin-fixed, paraffin-embedded tissue samples. Detailed clinicopathological data of thyroid cancer cases with RET fusions were collected. Results: Among 2300 thyroid cancer cases, RET fusions were exclusively found in PTC or differentiated high-grade thyroid carcinoma (DHGTC) cases (2234 cases), absent in other types (66 cases). Of the 2234 PTC or DHGTC cases, 113 (5.06%) exhibited RET fusions, including 100 primary cases. Coiled-coil domain containing 6 (CCDC6)-RET fusions predominated (78.0%, 78/100), with nuclear receptor coactivator 4 (NCOA4)-RET fusions representing 22.0% (22/100). NCOA4-RET fusions were more prevalent in patients aged 45 years and older (54.5% vs. 28.2%, p = 0.021) and DHGTC cases (p < 0.05) and associated with higher rates of lymph node metastases (90.9% vs. 67.9%, p = 0.032). CCDC6-RET fusion exhibited a higher prevalence of Hashimoto's thyroiditis (HT) (67.9% vs. 22.7%, p < 0.001) and elevated thyroglobulin antibody levels (14.11 [1.86–174.32] IU/mL vs. 2.01 [1.14–15.41] IU/mL, p = 0.018). Moreover, CCDC6-RET fusion predominantly occurred in classical PTC (56.4%, 44/78) and infiltrative follicular PTC (17.9%, 14/78), whereas NCOA4-RET fusion was more frequent in classical PTC (36.4%, 8/22), solid PTC (27.3%, 6/22), and DHGTC (27.3%, 6/22). RET fusions with compound mutations were associated with older age (≥45 years) and bilateral thyroid involvement. Follow-up data showed a higher recurrence rate in the RET fusion group compared with the BRAFV600E mutation group (5.0% vs. 0.0%, p = 0.018). Although the NCOA4-RET group showed a numerically higher recurrence rate compared with CCDC6-RET (9.1% vs. 3.8%), this difference was not statistically significant (p = 0.559). Conclusions:RET fusions are specific to PTC or DHGTC cases among Chinese thyroid cancer cases. CCDC6-RET and NCOA4-RET fusions exhibited distinct clinicopathological features, with NCOA4-RET being more aggressive. [ABSTRACT FROM AUTHOR]

Objective: Increased frequency of autoimmune thyroid disease, particularly Hashimoto's thyroiditis (HT) was reported several studies in the literature, in individuals with childhood-onset systemic lupus erythematosus (cSLE). Our study aimed to investigate the prevalence and contributing factors of thyroid dysfunction and HT among cSLE patients. Methods: Thyroid function tests were obtained cross-sectionally from cSLE patients. Demographic, clinical, and laboratory characteristics and activity scores were collected from medical records. Patients diagnosed with cSLE were compared to the healthy control group for the frequency of thyroid dysfunction. The Mann-Whitney U, independent samples t test, and the Chi-square or Fisher's exact test were used to compare study groups. A p -value below 0.05 was considered statistically significant. Results: Out of 73 cSLE patients, 14 (19.1%) had subclinical hypothyroidism, 9 (12.3%) had clinical hypothyroidism, 12 (16.4%) were diagnosed with HT, and 12 (16.4%) had a family history of HT. Thyroid USG was performed in 5 euthyroid patients and 1 borderline subclinical hypothyroid patient with positive thyroid autoantibody and reported as diffuse heterogeneous echogenicity enlargement in the thyroid gland. There were no significant differences in clinical and laboratory data or medication used between the groups with and without HT; however, patients with HT had a higher frequency of clinical hypothyroidism and family history of HT. Cumulative prednisolone dose was significantly lower in patients diagnosed with HT. The frequency of HT was considerably higher in patients with cSLE compared to the healthy control group. Conclusion: The results demonstrate an increased incidence of HT in cSLE patients, even if they are euthyroid, and recommend that cSLE patients be screened more frequently. [ABSTRACT FROM AUTHOR]

Objectives/introductionMethodsResultsConclusionTo evaluate the presence and concentration of antithyroid peroxidase (TPOAb) and antithyroglobulin (TGAb) antibodies at the onset of Hashimoto’s Thyroiditis (HT) and their association with disease characteristics and reproductive parameters before and after diagnosis.This is a cross-sectional study with 65 women with HT followed in an outpatient clinic. The data was collected by interviews and review of medical records. The variables were characteristics of the disease; TPOAb and TGAb measurements; pregnancies; live children; premature births; pregnancy losses and infertility. We used the chi-square or Fisher’s exact tests, the Mann–Whitney test and the Spearman correlation. The significance level was set at 5%.The mean age at diagnosis was 38 (SD ± 11.1) years and the duration of the disease was 7.5 (SD ± 5.3) years; 46% of the women reported infertility periods. 59/65 (90.7%) women had TPOAb and 42 (64.6%) had TGAb antibodies. Comparison between the groups with and without TPOAb or TGAb showed no differences between all variables studied. We found positive correlations between TPOAb concentration and preterm births and thyroid volume; and TGAb concentration was positively correlated with age.The presence of autoantibodies did not influence reproductive parameters; TPOAb concentration was correlated with premature births and thyroid volume. [ABSTRACT FROM AUTHOR]

Purposes: To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Methods: Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. Results: There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Conclusion: Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively. [ABSTRACT FROM AUTHOR]

Background: Epigenetic age accelerations (EAAs) are a promising new avenue of research, yet their investigation in subacute thyroiditis (SAT) remains scarce. Our study endeavors to fill this void by exploring the potential causal association between EAAs and SAT. Methods: Our study utilized publicly available genome-wide association study (GWAS) data of European ancestry to conduct a bidirectional Mendelian randomization (MR) study. Five MR methods were employed to measure causal association between EAAs and SAT multiple analyses were utilized to perform quality control. Results: Our study evaluated causal association between SAT and four EAAs, included GrimAge acceleration (GrimAA), Hannum age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), intrinsic epigenetic age acceleration (IEAA). Results showed that there is a significant causal association between PhenoAA and SAT (OR 1.109, 95% CI 1.000–1.228, p = 0.049, by IVW method). On the contrary, SAT was associated with IEAA (OR 0.933, 95% CI 0.884–0.984, p = 0.011, by IVW method; OR 0.938, 95% CI 0.881–0.998, p = 0.043, by weighted median method). Leave-one-out sensitivity analysis, heterogeneity test, pleiotropy test, and MR-PRESSO analysis provide good quality control. Conclusion: The bidirectional MR analysis concluded that an increase in PhenoAA was correlated with a higher risk of SAT, indicating a potential causal relationship between PhenoAA and risk of SAT. Conversely, SAT was found to be closely associated with IEAA, suggesting that SAT may accelerate the aging process. Slowing down biological aging has emerged as a new research direction in curbing SAT. [ABSTRACT FROM AUTHOR]

Introduction: Activation of the MAPK pathway by genetic mutations (such as BRAF and RET) initiates and accelerates the growth of papillary thyroid carcinoma (PTC). However, the correlation between genetic mutations and clinical features remains to be established. Therefore, this study aimed to retrospectively analyze major genetic mutations, specifically BRAF mutations and RET rearrangements, and develop a treatment algorithm by comparing background and clinical characteristics. Method: One hundred thirteen patients with primary PTC were included in this study. BRAF mutations were detected via Sanger sequencing and RET rearrangements were detected via fluorescence in situ hybridization (FISH) analysis, and reverse transcription polymerase chain reaction (RT-PCR). The patients were categorized into two groups based on the presence of BRAF mutations and RET rearrangements and their clinical characteristics (age, sex, TNM, stage, extratumoral extension, tumor size, unifocal/multifocal lesions, vascular invasion, differentiation, chronic thyroiditis, preoperative serum thyroglobulin level, and 18F-fluorodeoxyglucose (FDG) uptake) were compared subsequently. Result: After excluding unanalyzable specimens, 80 PTC patients (22 males and 58 females, mean age: 57.2 years) were included in the study. RET rearrangements were positive in 8 cases (10%), and BRAF mutation was positive in 63 (78.6%). The RET rearrangement group was significantly associated with younger age (p = 0.024), multifocal lesion (p = 0.048), distant metastasis (p = 0.025) and decreased 18F-fluorodeoxyglucose uptake (p < 0.001). The BRAF mutation group was significantly associated with unifocal lesions (p = 0.02) and increased 18F-FDG uptake (p = 0.004). Conclusion: In this study, an increase in M classification cases was found in the RET rearrangements group. However, genetic mutations were not associated with the clinical stage, and no factors that could be incorporated into the treatment algorithm were identified. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study was to evaluate the prevalence and impact of impaired thyroid-stimulating hormone (TSH) levels on the reproductive outcomes of in vitro fertilization patients diagnosed with endometriosis and compared to controls without endometriosis. Design: This is a retrospective cohort study on prospectively collected data. Setting: The study was conducted at tertiary care university hospital. Participants: Participants were infertile women with histopathological diagnosis of endometriosis. Methods: For 12 months (January 2018 to January 2019), women were deemed suitable and subsequently divided according to serum TSH levels above or below 2.5 mIU/L and compared to patients without endometriosis. Needed sample size was at least 41 patients for each cohort of women. Co-primary outcomes were the live birth rate (LBR), clinical pregnancy rate (CPR), and pregnancy loss rate (PLR). Results: Overall, 226 women (45 with endometriosis and 181 controls without endometriosis) were included. Diagnoses of Hashimoto thyroiditis were significantly more frequent in women with rather than without endometriosis (14/45 [31.1%] vs. 27/181 [14.9%]; p = 0.012). Similarly, in women with endometriosis, Hashimoto diagnosis rates were higher with TSH ≥2.5 mIU/L compared to TSH <2.5 mIU/L (9/15 [60%] vs.5/30 [16.6%]; p = 0.001) so were the Hashimoto diagnosis rates in control group (women without endometriosis) with TSH ≥2.5 mIU/L compared to TSH <2.5 mIU/L (17/48 [35.4%] vs. 10/133 [7.5%], respectively; p = 0.001). Effect size analysis confirmed an increased risk of Hashimoto thyroiditis in women with endometriosis and TSH ≥2.5 mIU/L compared to women with endometriosis and TSH <2.5 mIU/L (risk ratio [RR] 3.60 [95% CI 1.46–8.86]) and in women with endometriosis and TSH ≥2.5 mIU/L compared to non-endometriotic euthyroid patients (RR 7.98 [95% CI 3.86–16.48]). Dysmenorrhea risk was higher in endometriotic euthyroid women compared to euthyroid patients with no endometriosis (RR 1.87 [95% CI 1.21–2.87]). The risk was still increased in euthyroid women with endometriosis relative to dysthyroid women with no endometriosis (RR 1.97 [95% CI 1.11–3.50]). There were no significant differences between the four groups for CPR, LBR, PLR and retrieved oocytes, immature oocytes, degenerated and unfertilized oocytes, cultured blastocysts, embryos and transferred embryos. Limitations: Limitations of the study were retrospective design, limited sample size, and use of different ovarian stimulation protocol. Conclusions: Thyroid autoimmunity seems more common in women with endometriosis and TSH over 2.5 mIU/L. However, there was no significant impact on in vitro fertilization and reproductive outcomes related to the coexistence of endometriosis, Hashimoto disease, and higher TSH levels. Due to limitations of the study, additional evidence is required to validate the abovementioned findings. [ABSTRACT FROM AUTHOR]

Objective: Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer). Methods: We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)‐Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia. Results: MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00–1.02, p =.01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected. Conclusion: This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between peripheral blood microribonucleic acid (miRNA)-142-3p, miR-125a-5p levels and thyroid function and T helper cells (Th)1/Th2 and Th17/T regulatory cell (Treg) cells balance in patients with Hashimoto's thyroiditis (HT). Methods: 90 HT patients admitted to our hospital from January 2020 to August 2023 were selected as HT group and 90 healthy people in the same period were selected as control group, HT patients were divided into normal thyroid function group (26 cases), subclinical hypothyroidism group (31 cases) and clinical hypothyroidism group (33 cases) according to the degree of hypothyroidism. The levels of miR-142-3p and miR-125a-5p in peripheral blood were detected by real-time fluorescence quantitative polymerase chain reaction, thyroid function indexes [thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT)] were detected by enzyme-linked immunosorbent assay, the proportions of Th1, Th2, Th17 and Treg cells in peripheral blood were detected by flow cytometry, and the ratios of Th1/Th2 and Th17/Treg were calculated. The correlation between miR-142-3p, miR-125a-5p and thyroid function, Th1, Th2, Th17, Treg in peripheral blood of HT patients was analyzed by Pearson/Spearman correlation analysis. Results: The ratios of miR-142-3p, miR-125a-5p, TgAb, TPOAb, TSH, Th1, Th17, Th1/Th2 and Th17/Treg in peripheral blood in HT group were higher than those in control group, while the ratios of FT3, FT4, Th2 and Treg were lower than those in control group (P<0.05). The ratios of miR-142-3p, miR-125a-5p, TgAb, TPOAb, TSH, Th1, Th17, Th1/Th2 and Th17/Treg in peripheral blood in normal thyroid function group, subclinical hypothyroidism group and clinical hypothyroidism group increased in turn, while the ratios of FT3, FT, Th2 and Treg decreased in turn (P<0.05). Pearson/Spearman correlation analysis showed that, miR-142-3p and miR-125a-5p in peripheral blood of HT patients were positively correlated with TgAb, TPOAb, TSH, Th1, Th17, Th1/Th2 and Th17/Treg, and negatively correlated with FT3, FT4, Th2 and Treg (P<0. 05). Conclusions: The levels of miR-142-3p and miR-125a-5p in peripheral blood of HT patients are increase, which are relate to hypothyroidism and imbalance of Th1/Th2 and Th17/Treg cells. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48–0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3–4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16–2.04), 1.14 (95% CI: 0.82–1.58), 1.66 (95% CI: 1.40–1.97), 1.53 (95% CI: 1.35–1.75), and 1.24 (95% CI: 1.11–1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51–0.81) for CNND, 0.83 (95% CI: 0.73–0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58–0.86) for ETE, 0.84 (95% CI: 0.75–0.94) for AJCC Stage 3–4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66–1.90, p = 0.67) and 0.60 (95% CI: 0.28–1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) are a common and growing type of cancer treatment, but they can cause side effects. This study aims to understand these side effects in patients with kidney cancer and bladder cancer. We compared the types and severity of side effects between these two groups to determine if there are differences. We also compared them to other tumor types to see if there is a unique pattern. The findings will help doctors better predict and manage side effects. This will hopefully lead to improving patient care for those receiving ICI treatment. Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 1 February 2011 and 7 April 2022 at a comprehensive cancer center and its outreach clinics. Dichotomous outcomes were modeled using multivariable logistic regression. Survival outcomes were compared using multivariable Cox regression. Results: Among 3101 patients, 196 had renal cell carcinoma (RCC) and 170 had urothelial tumors. RCC patients were more likely to experience irAEs (OR 1.78; 95% CI 1.32–2.39), whereas urothelial carcinoma patients were not (OR 1.22; 95% CI 0.88–1.67). RCC patients were more prone to dermatitis, thyroiditis, acute kidney injury, and myocarditis, compared to other tumors, while urothelial carcinoma patients were not. The impact of irAEs on survival was not significantly different for GUcs compared to other tumors. Conclusions: RCC primaries have a significantly different irAE profile than most tumors, as opposed to urothelial primaries. Further, RCC was more likely to experience any irAEs. Heterogeneity of survival benefits by irAEs was not seen. [ABSTRACT FROM AUTHOR]

Les thyroïdites sont des affections courantes, le plus souvent bénignes et qui s'accompagnent d'une perturbation biologique du bilan thyroïdien. Néanmoins, leur résolution est parfois spontanée. Le terme "thyroïdite" regroupe plusieurs maladies caractérisées par l'inflammation de la glande thyroïdienne. Les patients décrivent souvent une douleur au cou qui est parfois associée à la présence d'un goitre. Les causes sont multiples. L'affection la plus commune est la thyroïdite d'Hashimoto, caractérisée par une hypothyroïdie. À l'inverse, la thyroïdite de Basedow est marquée par une hyperthyroïdie. Ce sont deux maladies auto-immunes dont le diagnostic repose, en plus du dosage de la thyréostimuline et des hormones thyroïdiennes T4L et T3L, sur le dosage d'anticorps spécifiques. Il existe également des thyroïdites d'origine iatrogène : l'amiodarone, un anti-arythmique dont la prescription est réservée aux cardiologues, est source de dysthyroïdie et nécessite une surveillance étroite. La thyroïdite du post-partum est une thyroïdite transitoire, parfois persistante, qui a lieu dans l'année qui suit une grossesse ou une fausse couche. Enfin, des thyroïdites sont d'étiologies infectieuses, telles que la thyroïdite subaiguë de De Quervain, d'origine virale. Le traitement mis en œuvre sera adapté à la cause de la thyroïdite et suivi par un endocrinologue. Thyroiditis are common conditions, mostly benign and accompanied by a biological disruption in the thyroid function. In fact, their resolution can sometimes be spontaneous. The term 'thyroiditis' encompasses several diseases characterized by inflammation of the thyroid gland. Patients often describe a neck pain that may be associated with the presence of a goiter. The causes are multiple. The most common condition is Hashimoto's thyroiditis, characterized by hypothyroidism. Conversely, Basedow's thyroiditis is characterized by hyperthyroidism. These are two autoimmune diseases whose diagnosis, in addition to the measurement of thyrotropin and thyroid hormones T4 and T3, relies on the measurement of specific antibodies. There are also iatrogenic thyroiditis: amiodarone, an antiarrhythmic drug prescribed by cardiologists, can cause thyroid dysfunction and requires close monitoring. Postpartum thyroiditis is a transient, sometimes persistent thyroiditis that occurs within a year following a pregnancy or miscarriage. Finally, some thyroiditis have infectious origins, such as De Quervain's subacute thyroiditis, which is of viral origin. The treatment implemented will be tailored to the aetiology of the thyroiditis and monitored by an endocrinologist. [ABSTRACT FROM AUTHOR]

L'hypothyroïdie résulte d'une carence en hormones thyroïdiennes de manifestations cliniques variables, avec parfois un goitre pouvant nécessiter une échographie. Il s'agit le plus souvent d'un hypofonctionnement primaire de la thyroïde consécutif à une thyroïdite auto-immune ou médicamenteuse, voire à une carence en iode. Plus rarement, l'hypothyroïdie peut être centrale dans le cadre d'une insuffisance hypophysaire. Le diagnostic biologique de l'hypothyroïdie périphérique repose sur une TSH sérique élevée (normes : 0,4-4 mUI/L hors grossesse et personnes âgées). Une TSH comprise entre 4 et 10 mUI/L sera contrôlée à six semaines. À toute TSH d'emblée supérieure à 10 mUI/L ou toute TSH confirmée entre 4-10 mUI/L, on ajoutera un dosage en cascade de T4L pour établir le caractère avéré (T4L diminuée) ou fruste (T4L normale) de l'hypothyroïdie. Le diagnostic étiologique commence par le dosage des anticorps anti-thyroperoxydase (ATPO) complété du dosage des anticorps anti-thyroglobuline (ATG) si les ATPO sont négatifs, voire de la iodurie des 24 heures. Le traitement par L-thyroxine est systématique seulement en cas d'hypothyroïdie avérée, et évalué en suivant la TSH sérique à six semaines, puis en espaçant le suivi dès que la TSH sera normalisée de façon stable. Dans les autres situations, un simple suivi de la TSH est recommandé à un an. On associera un dosage de T4L en cas de TSH instable. Hypothyroïdism is a deficiency of thyroid hormones with variable clinical manifestations, sometimes with a goiter that may require an ultrasound scanning. It results mainly from primary thyroid dysfunction secondary to autoimmune or drug-induced thyroiditis, and sometimes to iodine deficiency. Less frequently, hypothyroidism can be central in the context of pituitary insufficiency. Bio-logical diagnosis of peripheral hypothyroidism is based on an elevated serum TSH (norms: 0.4-4 mIU/L excluding pregnancy and the elderly). A TSH of between 4-10 mIU/L will be checked at six weeks. To any TSH above 10 mIU/L or any TSH confirmed between 4-10 mIU/L, fT4 assay allows the distinction between proven hypothyroidism (decreased fT4) and sub-clinical hypothyroidism (normal T4L). The etiological diagnosis relies on anti-thyroperoxidase antibodies (ATPO) assay completed by anti-thyroglobulin antibodies (ATG) assay if negative, and 24-hours ioduria if necessary. L-thyroxine supplementation is systematic only in cases of proven hypothyroidism and assessed by monitoring the TSH at six weeks, then spacing the monitoring as soon as the TSH has stabilized. In all the other situations, a simple control of TSH assay is recommended at one year. A T4L dosage will be added in case of unstable TSH. [ABSTRACT FROM AUTHOR]

Bailing capsule (BLC), a drug that is clinically administered to modulate the autoimmune system, exhibits promising therapeutic potential in the treatment of thyroiditis. This study elucidates the chemical profile of BLC and its potential therapeutic mechanism in thyroiditis, leveraging network pharmacology and molecular docking techniques. Utilizing ultra‐high‐performance liquid chromatography coupled with linear trap‐Orbitrap mass spectrometry (UHPLC‐LTQ‐Orbitrap MS), 58 compounds were identified, the majority of which were nucleosides and amino acids. Utilizing the ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC QqQ MS/MS) strategy, 16 representative active components from six batches of BLCs were simultaneously determined. Network pharmacology analysis further revealed that the active components included 5′‐adenylate, guanosine, adenosine, cordycepin, inosine, 5′‐guanylic acid, and l‐lysine. Targets with higher connectivity included AKT1, MAPK3, RAC1, and PIK3CA. The signaling pathways primarily focused on thyroid hormone regulation and the Ras, PI3K/AKT, and MAPK pathways, all of which were intricately linked to inflammatory immunity and hormonal regulation. Molecular docking analysis corroborated the findings from network pharmacology, revealing that adenosine, guanosine, and cordycepin exhibited strong affinity toward AKT1, MAPK3, PIK3CA, and RAC1. Overall, this study successfully elucidated the material basis and preliminary mechanism underlying BLC's intervention in thyroiditis, thus laying a solid basis for further exploration of its in‐depth mechanisms. [ABSTRACT FROM AUTHOR]

Background/Aim: Hashimoto thyroiditis (HT) association with thyroid lymphoma is well established; however, the association with papillary thyroid cancer (PTC) is still unclear. Thyroid cancer incidence has shown an increasing trend in recent years. It is characterized by slow growth, making it generally amenable to successful treatment. Materials and Methods: We aimed to identify genes considered as promising biomarkers of the progression from thyroiditis to thyroid cancer in public gene expression datasets. Results: We identified 70 differentially expressed genes (DEGs) and used them to prioritize biological risk genes for thyroiditis and thyroid cancer. Statistics and a scoring system based on six functional annotations of significant biological impact identified four genes of interest: CXCR4, IL6ST, PPARG and TP53. Kaplan–Meier plots were used to assess the expression levels related to overall survival. Furthermore, a manual bibliographic search was carried out for each gene, and a protein–protein interaction (PPI) network was built to verify their known associations. Conclusion: The results showed that all four genes (CXCR4, IL6ST, PPARG, TP53) were highly relevant to thyroiditis and thyroid cancer, thus making them worthy of further investigation to understand their relationship with these two diseases. [ABSTRACT FROM AUTHOR]

Background and Objectives: The available research suggests that dietary patterns with high inflammatory potential, as indicated by a high DII score, may exacerbate inflammation and potentially influence thyroid function. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of a diet and thyroid function in adults with Hashimoto's thyroiditis (HT). Materials and Methods: A total of 149 adults diagnosed with Hashimoto's thyroiditis were enrolled in this observational, cross-sectional, multicenter study. The Dietary Inflammatory Index (DII®) was calculated using a 141-item food frequency questionnaire (FFQ). The serum levels of the thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPO-Ab), and high-sensitivity C-reactive protein (hsCRP) were determined. Results: The DII® scores ranged from −3.49 (most anti-inflammatory) to +4.68 (most pro-inflammatory), whereas three DII® tertile ranges were defined as <−1.4, −1.39 to +1.20, and >+1.21, respectively. Participants in tertile 1 (more anti-inflammatory diet) had significantly higher levels of fT4 than those adhering to a more pro-inflammatory diet (p = 0.007). The levels of hsCRP and TSH appeared to increase with increasing the DII® score, but without statistical significance. A significant association was found between the DII® and TSH (β = 0.42, p < 0.001) and between DII® and free thyroxine (β = 0.19, p < 0.001). After adjustment for age, gender, energy intake, and physical activity, a significant positive correlation remained between the DII® and TSH (β = 0.33, p = 0.002) and between the DII® and body mass index (BMI) (β = 0.14, p = 0.04). Conclusions: Adherence to an anti-inflammatory diet appears to be beneficial in patients with Hashimoto's thyroiditis, suggesting that dietary modification aimed at lowering DII® levels may be a valuable strategy to improve clinical outcomes in these patients. [ABSTRACT FROM AUTHOR]

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Branchiogenic fistulas are congenital alterations that affect the cervical compartments. Those of the fourth branchial cleft are rarest and can begin late with very serious complications. The suppurative thyroiditis can be a complication of these alterations. We describe a case of 3-year-old girl with high fever, left cervical swelling and increased inflammation indices. The neck ultrasound showed an abscess of the left thyroid lobe and a fluid mass with aerial content in laterocervical region. On MRI, the fluid mass extended from the left piriform sinus to the mediastinum. Fluoroscopy also highlighted a fistolose trait that extended from the left side wall of the esophagus, anteriorly towards the trachea. Treatment of these pathologies must be early and a late diagnosis can put patients' lives at risk.

Nivolumab is now preferred as first-line and second-line treatment for advanced esophageal cancer, while regorafenib improves survival in refractory gastroesophageal cancer. The combined use of nivolumab and regorafenib has shown promising results. Nivolumab-induced thyroid dysfunction is a common immune-related adverse event (irAE), while type 1 diabetes mellitus induced by immune checkpoint inhibitors is rare and usually permanent. It is unclear whether the combination of regorafenib and nivolumab increases the risk of irAEs. We report a patient with recurrent esophageal squamous cell carcinoma who was treated with nivolumab plus regorafenib and developed thyroiditis and diabetic ketoacidosis. The rechallenge was successful, and the patient achieved a good treatment response.

Abstract Introduction Differentiating malignant thyroid nodules from benign ones is challenging. Sonography is a non‐invasive modality that can be helpful in this regard and is far better than invasive methods like fine needle aspiration (FNA). This study aimed to assess the diagnostic value of colour Doppler ultrasonography in distinguishing malignant and benign nodules of thyroid gland. Methods The study involved patients with thyroiditis and thyroid nodules, who underwent sonography. Ultrasound findings were assessed. All the nodules were classified according to the FNA into malignant, follicular nodules and lymphatic. Then, sonography findings were compared between these three groups. Results There were 216 nodules, including 108 (50%) malignant nodules, 80 (37%) benign and 28 (13%) lymphatic follicles, were evaluated. Micro‐calcification was present in 50 (46.3%) malignant cases, 11 (13.7%) benign cases and 2 (2.1%) lymphatic follicles. Decreased or mixed vascularity was reported in 43 (69%) malignant nodules, 4 (5%) benign cases and 7 (25%) lymphatic follicles. Also, 9.7% and 42% of malignant and benign nodules had peripheral circular vascularity, respectively; however, none of the lymphatic follicles had this finding. With 89% specificity, 49% sensitivity and 73.5% accuracy, calcification with or without decreased or mixed vascularity could differentiate benign and malignant nodules. Conclusion Decreased or mixed vascularity with or without calcification shows high sensitivity in differentiating malignant and benign nodules.

Studies have been conducted on the relationship between depression and thyroid diseases and function, its causal relationship remains unclear. Using summary statistics of genome-wide association studies of European and East Asian ancestry, we conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid function (European: normal range TSH, T4, T3, fT4, TPOAb levels and TPOAb-positives; East Asian: T4) and thyroid diseases (hypothyroidism, hyperthyroidism, and Hashimoto's thyroiditis), and used Mediation analysis to evaluate potential mediators (alcohol intake, antidepressant) of the association and calculate the mediated proportions. It was observed a significant causal association between MDD on hypothyroidism (P = 8.94 × 10−5), hyperthyroidism (P = 8.68 × 10−3), and hashimoto's thyroiditis (P = 3.97 × 10−5) among European ancestry, which was mediated by Alcohol intake (alcohol intake versus 10 years previously for hypothyroidism (P = 0.026), hashimoto's thyroiditis (P = 0.042), and alcohol intake frequency for hypothyroidism (P = 0.015)) and antidepressant (for hypothyroidism (P = 0.008), hashimoto's thyroiditis (P = 0.010)), but not among East Asian ancestry (P MDD-hypothyroidism = 0.016, but β direction was different; P MDD-hyperthyroidism = 0.438; P MDD-hashimoto ' s thyroiditis = 0.496). There was no evidence for bidirectional causal association between thyroid function mentioned above and MDD among both ancestry (all P > 0.05). We importantly observed a significant causal association between MDD on risk of hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, and Alcohol intake and antidepressant as mediators for prevention of hypothyroidism, hashimoto's thyroiditis attributable to MDD. • We conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid diseases among European and East Asian ancestry and Mediation analysis to evaluate potential mediators (alcohol intake and antidepressant). • It was observed a significant causal association between MDD on hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, in which MDD on hypothyroidism and hashimoto's thyroiditiswas were mediated by Alcohol intake and antidepressant, but not among East Asian ancestry. • These findings may lead to a shift in personalizing treatment in the future. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of acute suppurative thyroiditis (AST) in an adult with type 1 diabetes. AST is a rare condition, more commonly seen in children, and is considered an endocrine emergency with a mortality rate ranging from 3.7% to 9.0%. The patient initially presented with symptoms of subacute thyroiditis (SAT) but rapidly progressed to septic shock, highlighting the challenges in differentiating between the two conditions. The case also highlights the rare occurrence of AST as a presentation of disseminated methicillin-resistant Staphylococcus aureus (MRSA) infection in a patient with type 1 diabetes, without additional immunocompromising factors. [Extracted from the article]

Objective This study investigated the onset and the choice of treatment in children with very early onset of type 1 diabetes mellitus (T1D). Methods The study included 5,763 patients from the German Diabetes Patient Follow-up registry with onset of T1D in the first 4 years of life from January 2010 – June 2022. The analysis included diabetes-specific parameters, anthropometric data, and mode of treatment at onset, within the first and second year of T1D. Three groups were compared according to age at onset (G1: 223 patients 6–<12 months, G2: 1519 patients 12–<24 months, G3: 4001 patients 24–48 months). Results In 12.3% of all cases in childhood and adolescence, the incidence of diabetes in the first 4 years of life was rare. At the onset, clinical status was worse and diabetic ketoacidosis (DKA) rates were higher in G1 and G2 (52.3% and 46.5%, respectively) compared to G3 (27.3% (p<0.001)). G1 and G2 were significantly more likely to be treated with insulin pump therapy (CSII) 2 years after onset (98.1% and 94.1%, respectively)) compared to G3 (85.8%, p<0.001). Median HbA1c after 2 years did not differ between groups (G1: 7.27% (56.0 mmol/mol), G2: 7.34% (56.7 mmol/mol) and G3: 7.27% (56.0 mmol/mol)) or when comparing CSII vs MDI. The rate of severe hypoglycemia (SH) and DKA during the first 2 years of treatment did not differ among the three groups, ranging from 1.83–2.63/100 patient-years (PY) for DKA and 9.37–24.2/100 PY for SH. Children with T1D under 4 years of age are more likely to be diagnosed with celiac disease but less likely to have thyroiditis than older children with T1DM. Conclusions Young children with T1D had high rates of DKA at onset and were predominantly treated with insulin pump therapy during the first 2 years. The median HbA1c for all three groups was<7.5% (58 mmol/mol) without increased risk of SH or DKA. The use of continuous glucose monitoring (CGM) was not associated with lower HbA1c in children under 48 months. [ABSTRACT FROM AUTHOR]

Aim This study aimed to demonstrate the role of Epstein-Barr Virus (EBV) in papillary thyroid carcinomas (PTC) developing on the background of Hashimotoʼs thyroiditis (HT). Methods The presence of EBV in tumoral tissue, lymphocytes, and peritumoral normal thyroid tissue was investigated using the in situ hybridization method in paraffin blocks. The subtypes of PTC, tumor diameter, TNM stage, multifocality, invasion of thyroid capsule, perineural invasion, and muscular tissue invasion were identified and compared according to EBV involvement. Results Eighty-one patients with HT diagnosis, with 93.8% (n=76) female and 6.2% (n=5) male, were included in the study. Papillary microcarcinoma was the pathological diagnosis in 24.2% (n=15) of the cases. EBV was identified in 58.06% (n=36) of the tumor cells nuclei, 58.06% (n=36) in the tumor cell cytoplasm, 16.12% (n=10) in tumor infiltrative lymphocytes, and 53.2% (n=33) in normal parenchymal follicle epithelial cells (NPFEC). In the T2 stage, the rate of EBV nuclear positivity in patients was significantly higher (p=0.034). The classic variant of papillary carcinoma was accompanied by a significantly higher rate of EBV-negative NPFEC (67.6%, p=0.049). In multifocal tumors, EBV positivity was found to be significantly higher in lymphocytes in the surrounding tissues (58.3%, p=0.034). Conclusion A significant increase in EBV positivity in the surrounding tissue lymphocytes was observed in multifocal PTC developing on a background of HT. This suggests a possible association between HT and EBV. [ABSTRACT FROM AUTHOR]

Background/Objective: Autoimmune thyroid diseases (AITD) affect 2 to 5% of the general population. This study aimed to determine changes in activity of A-Tg and A-TPO antibodies before, during, and after pregnancy in women with previous AITD. Methods: This was a single-center study with a retrospective review of the medical records of 30 female patients aged 25–41 years who came to our endocrinology service in the city of Santo André, state of São Paulo, Brazil, to investigate thyroid diseases. The following data were reviewed: total triiodothyronine (totalT3), total thyroxine (totalT4), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-TSH receptor antibodies (anti-TSH receptor or anti-thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase (A-TPO), and anti-thyroglobulin (A-Tg)). These data were reviewed for 30 patients before and during the three trimesters of pregnancy and during the three months after pregnancy. Results: During gestation, we observed a progressive decrease in the blood values of A-TPO and A-Tg, which reached their lowest values in the third trimester of pregnancy, but after birth, they returned to values statistically equivalent to those before pregnancy. Analyzing the three trimesters and the post-pregnancy period, A-TPO increased 192% between the first trimester and postpartum (p = 0.009); it increased 627% between the second trimester and postpartum (p < 0.001); and it increased >1000% between the third trimester and postpartum (p < 0.001). There was no significant difference in the A-TPO values between the pre- and post-gestational periods (p = 1.00), between the first and second trimesters (p = 0.080), or between the second and third trimesters (p = 0.247). Conclusions: According to the results presented here, we observed changes in the activities of A-Tg and A-TPO antibodies during and after pregnancy in women with previous AITD. In women who intend to become pregnant, are pregnant, or have given birth within three months, it is essential to monitor A-TPO, A-Tg, and thyroid function as well as serum thyroid hormones and TSH to identify thyroid dysfunction in a timely manner and adjust the treatment strategy to avoid the deleterious effects of hypothyroidism on both mother and baby during and after pregnancy. [ABSTRACT FROM AUTHOR]

Background: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI]. Methods: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit. Results: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026]. Conclusions: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs. [ABSTRACT FROM AUTHOR]

Background: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV. Methods: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022. Results: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007). Conclusions: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases. [ABSTRACT FROM AUTHOR]

Background: To evaluate the malignancy risk of sonographic (US) indeterminate lymph node (LN)s at the central compartment in thyroid cancer patients with US‐thyroiditis (ST). Methods: Among the central compartments of suspicious, indeterminate, and probably benign LN US categories, the malignancy rates were compared between ST and non‐US‐thyroiditis (non‐ST) groups. Those of indeterminate category were compared with suspicious and probably benign categories. Results: At 531 central compartments from 349 patients, the malignancy rate was lower in ST group (34.4% [44/128]) than non‐ST group (43.4% [175/403]), although statistically not significant (p = 0.08). The malignancy rate of indeterminate category in ST group (35.7% [5/14]) was lower than non‐ST group (71.9% [23/32]) (p = 0.047). Within ST group, the malignancy rate of indeterminate category (35.7% [5/14]) did not differ from probably benign category (29.1% [30/103]) (p = 0.756), but was lower than suspicious category (81.8% [9/11]) (p = 0.042). Conclusions: The malignancy risk of US indeterminate LNs at the central compartment in thyroid cancer patients with US thyroiditis was lower than that in patients without US thyroiditis. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has been introduced as a standard of care for several cancers, and its use is on the rise. However, the enhanced immune system frequently causes immune-related adverse events. Depending on the affected organ and tissue and the severity of the toxicity, immunotherapy is generally held, and steroids or immunosuppressive agents are introduced, impacting cancer treatment. Therefore, prompt identification of toxicity at an early stage and multidisciplinary management are mandatory. Since imaging is crucial to guide clinicians in managing immune-related adverse events, this imaging-based review presents the most frequent complications identifiable on imaging. Clues for identification and the most important differential diagnoses are discussed to enhance knowledge among imaging specialists and clinicians regarding these complications. Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent within the first few months. Any organ and tissue can be affected, ranging from mild to life-threatening. While some manifestations are common and more often mild, such as dermatitis and colitis, others are rarer and more severe, such as myocarditis. Management depends on the severity, with treatment being held for >grade 2 toxicities. Steroids are used in more severe cases, and immunosuppressive treatment may be considered for non-responsive toxicities, along with specific organ support. A multidisciplinary approach is mandatory for prompt identification and management. The diagnosis is primarily of exclusion. It often relies on imaging features, and, when possible, cytologic and/or pathological analyses are performed for confirmation. In case of clinical suspicion, imaging is required to assess the presence, extent, and features of abnormalities and to evoke and rule out differential diagnoses. This imaging-based review illustrates the diverse system-specific toxicities associated with immune checkpoint inhibitors and chimeric antigen receptor T-cells with a multidisciplinary perspective. Clinical characteristics, imaging features, cytological and histological patterns, as well as the management approach, are presented with insights into radiological tips to distinguish these toxicities from the most important differential diagnoses and mimickers—including tumor progression, pseudoprogression, inflammation, and infection—to guide imaging and clinical specialists in the pathway of diagnosing immune-related adverse events. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of Kabuki syndrome (KS) complicated by severe immune thrombocytopenia (ITP) and autoimmune thyroiditis (AIT). KS is a congenital disorder associated with mutations in the KMT2D or KDM6A genes. The presence of autoimmune disorders, such as ITP and AIT, in KS patients is rare. The article presents a case study of a 9-year-old boy with KS who had a novel pathogenic KMT2D mutation, delayed development, organ malformations, and severe ITP and AIT. The study highlights the importance of mutation identification for predicting disease phenotypes and autoimmune complications in KS. [Extracted from the article]

Introduction Benign paroxysmal positional vertigo (BPPV) is the peripheral vestibular dysfunction that most affects people worldwide, but its etiopathogenesis is still not fully understood. Considering the etiological diversity, some studies highlight the association between BPPV and thyroid diseases. Objective To investigate the association between thyroid diseases and BPPV. Data Synthesis Systematic review and meta-analysis of epidemiological studies searched in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases. Studies that were fully available and investigated the association between BPPV and thyroid diseases were selected. The articles that composed the meta-analysis were analyzed using the dichotomous model, the Mantel-Haenszel statistical test, odds ratio (OR), and a 95% confidence interval (CI). Of the 67 articles retrieved from the databases, 7 met the eligibility criteria of the systematic review, and 4 had data necessary to perform the meta-analysis. Qualitative analysis revealed that the studies were conducted in the European and Asian continents. The predominant methodological design was the case-control type, and thyroid dysfunctions, hypothyroidism, and Hashimoto thyroiditis occurred more frequently. The meta-analysis showed no association between hypothyroidism and BPPV; however, there was a statistically significant relationship between Hashimoto thyroiditis and BPPV. Conclusion The meta-analysis results suggest a possible association between BPPV and Hashimoto thyroiditis. Nevertheless, we emphasize the need for further studies to elucidate the evidence obtained. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) has been considered a T cell-mediated autoimmune demyelinating disorder. Nuclear factor κB (NF-κB) is one of the master transcription factors that regulate the activity of inflammatory cells the present study aimed to investigate the NFKB/P65 mRNA levels in patients with MS and to assess its role in the prediction of Hashimoto' thyroiditis (HT). Methods: 50 patients with clinically definite relapsing-remitting multiple sclerosis (according to the McDonald criteria 2017) compared to 50 healthy age and sex-matched controls. Thyroid serum antibodies, IgG index (IgG), and oligoclonal band (OCB) were assessed. The relative expression of NFKB/P65 mRNA was measured using real-time quantitative PCR. Results: there were significantly higher values of NFKB/P65 mRNA levels in patients with HT (2.4±0.54) compared to other patients without HT (1.3±1.45) and control group (0.8±0.17), p <0 .001. Significant associations were confirmed between NFKB/P65 mRNA correlated to thyroid autoimmunity and MS manifestations, p <0. 001. Linear regression revealed that only FT4 and TSH were independent variables correlated with NFKB/P65 mRNA, p < 0.001. Regarding prediction of MS, ROC curve revealed that the sensitivity of NFKB/P65 mRNA was 96 %, and specificity was 88% at cutoff 0.98 with (95% CI = 0.909-0.999). Concerning HT prediction, the cutoff 1.42 with (95% CI = 0.843-1.000)with a sensitivity of 93.8 % and, a specificity of 87.4%. Conclusions: NFKB/P65 mRNA increased in patients with MS more specifically in HT. Thus, NFKB/P65 mRNA could be used as noninvasive prediction markers of MS and HT. [ABSTRACT FROM AUTHOR]

Objective: To investigate the ultrasonographic characteristics and risk factors of hypothyroidism in subacute thyroiditis diagnosed by different ultrasonography. Methods: 121 patients with subacute thyroiditis who were treated in our hospital from October 2022 to April 2023 were enrolled for the first thyroid ultrasound examination and clinical data were followed up for 6 months. The longitudinal and transverse section of the bilateral lobar thyroid gland was examined and recorded by conventional ultrasound mode (2D, Doppler), and then the elastic imaging mode was activated for scanning. The general clinical data of subacute thyroiditis patients with hypothyroidism and those without hypothyroidism were compared, and the early ultrasonographic characteristics of two-dimensional, Doppler and elastic ultrasonography were compared. Univariate analysis and multivariate Logistic regression were used to analyze the risk factors of hypothyroidism in subacute thyroiditis patients. ROC curve was used to analyze the value of elastic modulus, strain rate, superior thyroid artery resistance index and velocity in predicting hypothyroidism in patients with subacute thyroiditis. Results: 121 patients with subacute thyroiditis were followed up in 115 cases, of which 29 had hypothyroidism and 86 had no hypothyroidism. The proportion of hypothyroidism was 25.22(29/115). According to statistical analysis, the period of hypothyroidism in subacute thyroiditis patients was related to the peak velocity and resistance index of the superior thyroid artery involved in the lateral lobe and focal area (P>0.05). The elastic modulus and strain rate of subacute thyroiditis patients with hypothyroidism were significantly higher than those without hypothyroidism (P>0.05). ROC curves of peak velocity, resistance index, elastic modulus and strain rate of thyroid artery in focal area for hypothyroidism in subacute thyroiditis patients showed that the AUC of elastic modulus was 0.898, the approximate exponent was 0.770, the sensitivity was 82.8%, the specificity was 94.2%, and the cut-off value was 114.5. The strain rate AUC was 0.74, the Jorden index was 0.422, the sensitivity was 72.4%, the specificity was 69.8%, and the cutoff value was 8.2. The resistance index AUC was 0.76, the Yoden index was 0.562, the sensitivity was 65.5%, the specificity was 90.7%, and the cut-off value was 0.66. The flow velocity AUC of superior thyroid artery was 0.838, the Yoden index was 0.608, the sensitivity was 72.4%, the specificity was 88.4%, and the truncation value was 25.94. The results of univariate analysis showed that the comparison of FT3, FT4, TRAb, ESR and hs-CRP between subacute thyroiditis and no thyroiditis showed statistical significance(P<0.05). The results of Logistic regression analysis indicated that elevated FT4, TRAb, ESR, and hs-CRP were risk factors for hypothyroidism in subacute thyroiditis (P<0.05). Conclusion: The combination of two-dimensional ultrasound, Doppler ultrasound and elastic ultrasound can predict hypothyroidism early after subacute thyroiditis. The risk factors for hypothyroidism in subacute thyroiditis are levels increased of FT4, TRAb, ESR and hs-CRP. [ABSTRACT FROM AUTHOR]

Background. In December 2019, the World Health Organization was notified about cases of pneumonia of unknown etiology originating in Wuhan, Hubei province, China. Hashimoto’s thyroiditis and other thyroid disorders including Graves’ disease affects almost 5 % of the general population. Hashimoto’s thyroiditis is a chronic disease in which the body interprets the thyroid gland and its hormone products as threats, therefore producing special antibodies that target thyroid cells, thereby destroying them. It may present with hypothyroidism or hyperthyroidism and with or without goiter. Basic questions in the consideration of a clinical case: what is COVID-19, and health complications? What concerns are related to pain in the front of the neck? How much has COVID-19 affected the occurrence of thyroid problems? Сase report. A 40-year-old man presented to the infectious disease clinic with a fever (37.9 °C), sore throat, body aches, and lethargy for 3 days on January 25, 2021. Due to the clinical features and the COVID-19 pandemic, a nasopharyngeal swab was used for sampling, and SARS-CoV-2 test was positive (mRNA in real time RT-PCR). On the 13th day, the patient’s general condition improved, but he complained of sore throat. On re-examination, we noticed a slight tenderness in the neck in the thyroid area. On thyroid ultrasound, a heterogeneous thyroid gland with ill-defined bilateral hypoechoic areas revealed subacute thyroiditis. The same patient presented to the infectious clinic with a fever (37.1 °C), sore throat, body aches and fatigue on June 28, 2022. After 5 days, the test for SARS-CoV-2 was negative, but, after one month of recovery, blood samples were analyzed to identify the functional state of the thyroid gland, and we obtained results with high values of thyroid-stimulating hormone. Conclusions. COVID-19 is a new disease for which larger-scale research is still ongoing, potential complications of COVID-19 and organ involvement are still being elucidated in the literature. Pain in the front of the neck, which can be combined with the upper part of the respiratory tract, especially in the conditions of COVID-19, should not be overlooked and requires further examinations. Subacute thyroiditis is a rare complication of COVID-19 that should be considered, especially in the progression of COVID-19 and the appearance of Hashimoto’s thyroiditis. [ABSTRACT FROM AUTHOR]

Background. Autoimmune thyroid diseases (AITDs), which include diffuse toxic goiter (DTG), or Graves’ disease, and autoimmune thyroiditis (AIT), are the most common organ-specific autoimmune diseases. Since recently the population of Ukraine is in a state of chronic stress associated with military operations on the territory of our country, it is important to clarify the nature of stress impact on cellular immunity in patients with autoimmune thyroid pathology. The purpose of the study was to establish the features of the cellular link of the immune response to stress in patients with autoimmune thyroiditis and diffuse toxic goiter. Materials and methods. Sixty patients with AITDs were examined in the clinic of V. Danilevsky Institute for Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine, 32 patients with AIT and 28 with DTG. In 24 cases, AITDs were newly diagnosed during the armed conflict (12 patients with DTG and 12 patients with AIT), and in 36 cases, the disease had a long course (16 patients with DTG and 20 patients with AIT, the manifestation took place until 2022). The relative (%) levels of CD3, CD4, CD8, CD16 and CD22 were determined in order to characterize immune homeostasis in patients with AITDs. Immunoregulatory indices were calculated as integral criteria of regulatory and effector links of immunity: suppression — CD4/CD8 as one of the key indicators of immune status, as well as indices of B cell help — CD4/CD16 and CD8/CD16. Results. The presence of DTG newly diagnosed in wartime is accompanied by a significant decrease in CD3 compared to the long-term course (55.67 ± 1.08 vs. 59.12 ± 1.14, P < 0.05). At the same time, in the group of patients with AIT newly diagnosed during military operations, a decrease in CD3 was less pronounced than on the background of DTG (58.30 ± 2.12 vs. 55.67±1.08). The wartime factor contributes to a more pronounced decrease in CD3 against the background of DTG versus AIT (55.67 ± 1.08 vs. 58.30 ± 2.12). Against the background of DTG and AIT in sub- groups with newly diagnosed disease, CD4 levels were higher than in the long-term course (36.33 ± 1.47 vs. 38.87 ± 1.12 in DTG and 35.35 ± 1.08 vs. 36.33 ± 1.47 in AIT). CD16 was lower in patients with DTG when the disease was detected during military operations and probably differed from the group with a long course of the disease (16.58 ± 0.94 vs. 18.68 ± 0.82, Р < 0.05). CD22 level was significantly lower in patients with DTG newly diagnosed during the war than at the long course (20.00 ± 1.01 vs. 23.19 ± 1.09, P < 0.05). The groups of patients with AIT or DTG newly diagnosed during the war had no significant difference in the levels of CD22 but on the background of AIT, the indicators were higher than in DTG (22.53 ± 1.41 vs. 20.00 ± 1.01). At the same time, with a long course of AIT and DTG, CD22 levels were higher in the DTG group (21.65 ± 1.58 vs. 23.19 ± 1.09). Conclusions. In patients with DTG and AIT, indicators of the cellular immune response have a multidirectional orientation, which depends, among other things, on the time of the disease and the stress that caused it. Immunoregulatory indices of suppression and B cell help significantly differ depending on the type of autoimmune disease and the time of its manifestation. [ABSTRACT FROM AUTHOR]