Clinical and molecular study of patients with thyroid dyshormogenesis and variants in the thyroglobulin gene.

Introduction: Defects in any thyroid hormone synthesis steps cause thyroid dyshormonogenesis (THD). THD due to thyroglobulin (TG) gene variants is a cause of congenital hypothyroidism (CH) with a wide clinical spectrum, ranging from mild to severe permanent hypothyroidism. We present high-throughput sequencing results of patients with TG variants. Methods: A CH high-throughput sequencing-panel of the main genes involved in the regulation of thyroid hormonogenesis was performed to identify those TG variants that may be related to patient THD phenotype. Results: We identified 21 TG gene variants in 19 patients (11.8%) which could explain their phenotype. Ten of those (47.6%) were not previously described. CH was biochemically severe in these 19 patients. Eight of them were reevaluated after one month of discontinuing LT4 treatment and all had severe permanent hypothyroidism. We also identified another 16 patients who presented heterozygous TG variants, of whom, at reevaluation, five had mild permanent and only one had severe permanent hypothyroidisms. Discussions: In this study, 10 novel and 11 previously reported variants in the TG gene have been identified that could explain the phenotype of 19 patients from non-consanguineous families from a large THD cohort. Although not all these TG gene variants can explain all the patients' THD phenotypes, some of them had severe or mild permanent hypothyroidism at reevaluation.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. METHODS: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. RESULTS: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001. CONCLUSION: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

Evaluation of the value of combined thyroid function-related indexes in the prognosis prediction of patients with differentiated thyroid cancer.

This study aims to evaluate the prognostic significance of thyroid function-related indices in patients with differentiated thyroid cancer (DTC). This retrospective analysis included 90 patients diagnosed with DTC and treated at our hospital from January 2010 to January 2019. Patients were classified into 2 groups based on whole-body imaging results: 67 with a favorable prognosis and 23 with a poor prognosis. The study compared clinical data and thyroid function indices between these groups to assess their efficacy in prognostic prediction. Patients in the poor prognosis group had a higher occurrence of T3-4 stage cancer (P = .006) and ≥2 lymph node metastases (P = .019). Notably, levels of total thyroxine (TT4), thyroid-stimulating hormone (TSH), and thyroglobulin antibody (Tg-Ab) were significantly elevated in this group (P < .001 for each). Receiver operating characteristic analysis revealed substantial predictive accuracy for TT4, TSH, and Tg-Ab (area under curve of 0.747, 0.820, and 0.720, respectively). The columnar graphical model used for prediction demonstrated a high concordance index (C-index = 0.919), superior to single-indicator evaluations. Thyroid function indices, specifically TT4, TSH, and Tg-Ab, play a crucial role in the prognostic assessment of patients with DTC. The column-line diagram model effectively enhances prophetic prediction, aiding in clinical decision-making.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.

The Effect of Mediterranean Diet on Thyroid Gland Activity.

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korcula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.

The efficacy and assessment value of the level of thyroglobulin wash-out after fine-needle aspiration cytodiagnosis in the evaluation of lymph node metastasis in papillary thyroid carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and clinical value of US, FNAC,FNA-Tg and FNAC + FNA-Tg, as well as the cutoff values of FNA-Tg to evaluate LN metastasis. METHODS: We analyzed the diagnostic value of different US signs, the efficiency of US, FNAC, FNA-Tg and FNAC + FNA-Tg among the LN- and LN + groups, and the cutoff value of FNA-Tg to evaluate LN metastasis. We punctured LNs multiple times and measured the levels of FNA-Tg. Furthermore, the LNs were marked with immunohistochemical Tg and LCA to distinguish the presence of Tg in the para-cancerous tissue of the LNs. RESULTS: The s-Tg and FNA-Tg of the LN + group were higher than those of the LN- group (P = 0.018, ≤ 0.001). The LN + group had more abnormal US signs than the LN- group. The cutoff value of FNA-Tg was 3.2 ng/mL. US had a high sensitivity (92.42), but the specificity was not satisfactory (55.1). FNA-Tg had a higher sensitivity (92.42 vs. 89.39), specificity (100 vs. 93.88), and accuracy (92.42 vs. 83.27) than FNAC. However, the sensitivity of FNAC + FNA-Tg increased further, while the specificity and accuracy decreased slightly. The presence of Tg in the normal lymphocytes adjacent to the cancer was confirmed. CONCLUSION: Ultrasonography provides a noninvasive, dynamic, multidimensional assessment of LNs. With a cutoff value of 3.2 ng/mL, FNA-Tg has higher accuracy and a lower false-negative rate than various single diagnoses. However, FNAC combined with FNA-Tg does not cause additional pain to patients and offers a higher diagnostic efficacy and clinical value.

Thyroglobulin specific IgE and a possible link to suspected penicillin induced allergic skin manifestations - cross sectional study.

Porcine thyroglobulin was important in the discovery of alpha-Gal allergy. Here, the linkage of porcine thyroglobulin-specific IgE with IgE positivity to routinely assessed allergens and to the incoming diagnosis within a population of suspected atopic individuals is explored. IgE, IgA, total IgG and IgG subclasses to porcine thyroglobulin, IgE to bovine, human thyroglobulin and meat extract were measured with ELISA. The following correlations were observed in IgE binding to porcine and bovine thyroglobulin (r = 0.910, p = 1x10-17), porcine and human thyroglobulin (r = 0.635, p = 4x10-6), human and bovine thyroglobulin (r = 0.746, p = 6x10-9) and porcine thyroglobulin and meat extract (r = 0.482, p = 0.0009). Only one out of ten samples which showed binding to porcine thyroglobulin in ELISA tested positive with ImmunoCAP alpha-Gal, implying different epitope/s. Increased IgE binding was detected towards a more electronegative fraction of porcine thyroglobulin separated according to charge and the binding could be partially inhibited by galactose. Anti-thyroglobulin IgE was found in 29.7% of the population, in subjects who were significantly younger, p < 0.0001 and it occurred more frequently in patients referred for testing penicillin specific IgE (OR 2.48, p = 0.0059) and were negative. IgE specific to porcine, bovine and possibly human thyroglobulin may be implicated in post-infectious skin manifestation misinterpreted as penicillin allergy.

Efficacy of Empirical 131 I Radioiodine Therapy in Well-Differentiated Thyroid Carcinoma Patients With Thyroglobulin-Elevated Negative Iodine Scintigraphy Syndrome : A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to perform a systematic review and meta-analysis on the efficacy of empirical high-dose radioiodine therapy in treating differentiated thyroid cancer patients with thyroglobulin (Tg)-elevated negative iodine scintigraphy (TENIS) syndrome. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant studies published until April 2022. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and registered in an international prospective register of systematic reviews (PROSPERO). Meta-analyses of proportions and odds ratios were performed to assess the beneficial effect of empirical high-dose radioiodine therapy in patients with TENIS syndrome. Subgroup analysis was also performed according to the presence of micrometastasis or macrometastasis. RESULTS: We identified 14 studies including 690 patients who received empirical high-dose radioiodine therapy for TENIS syndrome. Those who had micrometastasis exhibited additional lesions not previously observed on diagnostic whole-body scan (prop = 0.64, 95% confidence interval [CI], 0.51-0.77) and had reduced serum Tg levels (prop = 0.69; 95% CI, 0.52-0.84) after empirical radioiodine treatment. No such findings were observed among patients with macrometastasis. Moreover, we found that the empirical radioiodine treatment group had lower serum Tg levels than did controls (odds ratio = 0.27; 95% CI, 0.09-0.87), which suggests a lower risk of disease progression. CONCLUSIONS: Our findings indicate that empirical high-dose radioiodine therapy promoted beneficial effects and could be recommended for patients with TENIS syndrome, especially those with micrometastasis.

Identification of southern Taiwan genetic variants in thyroid dyshormonogenesis through whole-exome sequencing.

Thyroid dyshormonogenesis (TDH) is responsible for 15%-25% of congenital hypothyroidism (CH) cases. Pathogenetic variants of this common inherited endocrine disorders vary geographically. Unraveling the genetic underpinnings of TDH is essential for genetic counseling and precise therapeutic strategies. This study aims to identify genetic variants associated with TDH in Southern Taiwan using whole exome sequencing (WES). We included CH patients diagnosed through newborn screening at a tertiary medical center from 2011 to 2022. Permanent TDH was determined based on imaging evidence of bilateral thyroid structure and the requirement for continuous medication beyond 3 years of age. Genomic DNA extracted from blood was used for exome library construction, and pathogenic variants were detected using an in-house algorithm. Of the 876 CH patients reviewed, 121 were classified as permanent, with 47 (40%) confirmed as TDH. WES was conducted for 45 patients, and causative variants were identified in 32 patients (71.1%), including DUOX2 (15 cases), TG (8 cases), TSHR (7 cases), TPO (5 cases), and DUOXA2 (1 case). Recurrent variants included DUOX2 c.3329G>A, TSHR c.1349G>A, TG c.1348delT, and TPO c.2268dupT. We identified four novel variants based on genotype, including TSHR c.1135C>T, TSHR c.1349G>C, TG c.2461delA, and TG c.2459T>A. This study underscores the efficacy of WES in providing definitive molecular diagnoses for TDH. Molecular diagnoses are instrumental in genetic counseling, formulating treatment, and developing management strategies. Future research integrating larger population cohorts is vital to further elucidate the genetic landscape of TDH.

Comparative study of the effects of different surface-coated silver nanoparticles on thyroid disruption and bioaccumulation in zebrafish early life.

The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 µg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28-2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO3, PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease.

Determination of the levels and possible associations of alpha2-macroglobulin with autoantibodies in the serum of patients with various forms of autoimmune thyroiditis.

Antibodies to thyroid peroxidase (AB-TPO), antibodies to thyroglobulin (AB-TG), and the content of α2-macroglobulin (α2-MG) have been studied in serum samples of patients with autoimmune thyroiditis (AIT). All the patients were divided into 3 groups depending on age: 25-35, 36-50, 51-65 years. We found a significant change in the thyroid panel parameters in AIT, but without significant changes in the average concentration of α2-MG in the age groups of patients. This may be due to the accumulation and retention of complexes of defective forms of α2-MG in the circulation associated with their decreased ability to bind to receptors.

Prognostic value of postoperative anti-thyroglobulin antibody in patients with differentiated thyroid cancer.

Purpose: Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. Methods: We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Results: Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb ≤47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Conclusion: Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients.

A homogeneous electrochemiluminescence immunoassay platform based on carbon quantum dots and magnetic beads enrichment for detection of thyroglobulin in serum.

Considering the high probability of recurrence or metastasis after thyroidectomy, it is meaningful to develop a rapid, sensitive and specific method for monitoring thyrophyma-related biomarkers. In this study, a homogeneous electrochemiluminescence immunoassay (HO-ECLIA) coupled with magnetic beads (MBs)-based enrichment tactic was established for the determination of thyrophyma-related thyroglobulin (Tg). Importantly, owing to the abundant surface groups and good biocompatibility of carbon quantum dots (CQDs), the incorporation of CQDs onto the Tg antigen surface was achieved, resulting in the formation of Tg-encapsulated CQDs (CQDs-Tg), which served not only as an ECL probe but as a biorecognition element. Under optimal experimental conditions, the proposed platform demonstrated a wide linear range from 0.01 to 100 ng·mL-1 with a detection limit of 6.9 pg·mL-1 (S/N = 3), and performed well in real serum sample analysis against interference. Collectively, the proposed platform exhibited the rapid response, satisfactory sensitivity and specificity toward Tg in complex serum milieu, and held a considerable potential for clinical prognosis monitoring of thyrophyma.

Changes in thyroid hormone concentrations over time in dogs with autoimmune thyroiditis.

OBJECTIVE: The objective of this study was to follow long-term changes in the concentration of thyroid hormones in dogs with subclinical thyroiditis. SAMPLES: Samples were obtained from 125 dogs with subclinical thyroiditis. The study population included 70 female and 55 male dogs. The mean testing interval was 3.9 years from initial testing (SD, 2.3 years; range, 1 to 9 years). METHODS: Dogs with subclinical thyroiditis were identified retrospectively using results from the Orthopedic Foundation for Animals Canine Thyroid Profile performed by the Endocrinology Section of the Michigan State University Veterinary Diagnostic Lab. Owners were invited to submit follow-up serum samples with their veterinarian along with a medical history form, including subsequent treatments. RESULTS: At the time of retesting, 30% of the dogs had progressed to hypothyroidism and/or were treated with thyroxine. Fifty percent maintained positive or equivocal thyroglobulin autoantibody (TgAA) results while remaining euthyroid. Fourteen percent of the dogs became TgAA negative and remained euthyroid. In 6% of the cases tested, proper medical histories were not available, and a final classification could not be determined. CLINICAL RELEVANCE: These results indicate that most dogs with elevated thyroglobulin autoantibodies either exhibit persistent autoimmune thyroiditis with continued risk of hypothyroidism or progress to hypothyroidism when monitored for more than 1 year. Thyroid function in dogs with subclinical thyroiditis should be monitored every 12 months or if there is change in the clinical presentation.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications.

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Effect of anti-thyroid antibodies on recurrent miscarriage: A meta-analysis.

SETTING: Previous studies addressed the association between anti-thyroid antibodies and recurrent miscarriage (RM), however, the role of anti-thyroid antibodies in RM patients is debatable. OBJECTIVES: Therefore, we conducted this meta-analysis and the aim of this current study was to assess whether anti-thyroid peroxidase (anti-TPO) and/or anti-thyroglobulin (anti-TG) antibody positivity was associated with RM. DESIGN: A meta-analysis was conducted. PARTICIPANTS: Recurrent miscarriage patients. METHODS: STATA 12.0 software were applied to compute odds ratios (ORs)/relative risks (RRs) and 95% CIs regarding association between anti-TPO and anti-TG antibodies and the prevalence of RM. RESULTS: N = 28 studies (8875 participants) explored effect of anti-thyroid antibodies on RM. Analysis of the 28 studies revealed significant association between anti-TPO, anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.02; 95% CI: 1.63-2.51, p < 0.001; I2 = 44.3%, p value for Q test = 0.004). Analysis of the 20 studies revealed significant association between anti-TPO antibodies and the prevalence of RM with a random effects model (OR/RR = 1.59; 95% CI: 1.25-2.03, p < 0.001; I2 = 43.1%, p value for Q test = 0.022). Analysis of the 14 studies revealed significant association between anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.25; 95% CI: 1.56-3.23, p < 0.001; I2 = 49.2%, p value for Q test = 0.019). CONCLUSIONS: Based on the currently available analysis, our findings suggest that women with anti-TPO and/or anti-TG antibodies have a higher risk of RM than that in negative antibody women. Further investigation is needed to better clarify the exact role of the anti-thyroid antibodies in RM and whether treatment is of benefit. LIMITATIONS: First, differences from various detection methods and reagents used in different studies may affect the diagnostic interpretation of anti-thyroid antibodies, which might influence the accuracy of this meta-analysis. Second, positive anti-thyroid antibodies seem likely to be part of a more general disorder of maternal immune system, due to restrictions of funding and condition, a complete autoantibody screening investigation is hardly to conduct in all participants, and this could be a possible limitation of all included studies. Third, there is no mention of thyroxine therapy on RM, making the meta-analysis even more limited.

Oncologic outcomes and surgical completeness of remote-access thyroidectomy: a systematic review and network meta-analysis.

BACKGROUND: The oncologic safety and surgical completeness of remote-access thyroidectomies are not yet clearly established. This study evaluates the oncologic outcomes and surgical completeness of three prevalent remote-access thyroidectomies: the gasless transaxillary approach (GTAA), bilateral axillo-breast approach (BABA), and transoral approach (TOA), in comparison with conventional transcervical thyroidectomy (CTT). METHODS: Literature searches were conducted in PubMed, EMBASE, and the Cochrane Library databases, covering the period from 2000 to 2023. Network meta-analyses were performed on selected studies, focusing on recurrence and surgical completeness. Surgical completeness was assessed using stimulated serum thyroglobulin levels and the count of retrieved lymph nodes. RESULTS: The review included 48 studies, encompassing a total of 16,356 patients. The number of retrieved lymph nodes was comparable among BABA, TOA, and CTT, while GTAA might be less effective. Stimulated serum thyroglobulin levels showed no significant differences across the four groups. However, the proportion of patients with stimulated thyroglobulin levels below 1.0 ng/mL was significantly lower in GTAA compared to the other groups. The overall recurrence rates were 1.31% for CTT, 0.89% for GTAA, 0.62% for BABA, and 0% for TOA, with no significant differences in recurrence rates when adjusted for follow-up duration. CONCLUSIONS: This study demonstrated that the oncologic outcomes of GTAA, BABA, and TOA are comparable to those of CTT, based on recurrence rates. In terms of surgical completeness, BABA and TOA showed equivalence to CTT, whereas GTAA might be inferior to the other techniques.

The clinical value of iodine-125 seed implantation in the treatment of iodine-refractory differentiated thyroid carcinoma.

Objective: To explore the clinical benefits of 125I seed implantation for iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods: A retrospective analysis was conducted on 36 patients with RAIR-DTC who underwent radioactive 125I seed implantation from January 2015 to February 2022, involving 73 lesions. Prescription dose: 80~120 Gy. All cases were followed up at 1, 3, and 5 months postoperatively to monitor changes in tumor size, serum thyroglobulin (Tg), and serum anti-thyroglobulin antibody levels in thyrotropin-inhibited states, pain scores, and postoperative adverse reactions. The data were processed and analyzed using IBM SPSS 26.0. LER (Local Effective Rate) and LCR (Local Control Rate) were expressed as n (%), tumor diameter, Tg, and pain scores were represented as Median (Q1, Q3). Pairwise comparisons were conducted using the Wilcoxon signed-rank test, and a p-value of less than 0.05 indicated statistical significance. Results: Tumor size was significantly reduced after treatment (all P < 0.001): tumor length diameters were 32.67 (17.70, 45.72) mm, 27.45 (12.30, 39.98) mm, 20.70 (11.98, 37.58) mm, and 20.39 (10.56, 33.20) mm in the preoperative, 1-, 3-, and 5-months postoperative periods, respectively. Additionally, two consecutive post-treatment results were more minor and statistically significant than the previous results (P < 0.001). The LER at 1-, 3-, and 5-months post-surgery was 23.73%, 38.98%, and 52.54%, respectively, while the LCR at the same time points was 98.31%, 96.61%, and 94.92%, respectively. Patients' serum Tg levels decreased significantly after surgery. (P < 0.001). Serum Tg levels were measured before surgery and 1-, 3-, and 5-months post-surgery. The results showed that serum Tg levels were 249.45 (79.39, 4718.75) ng/ml, 193.40 (44.53, 2829.00) ng/ml, 192.10 (25.58, 1758.00) ng/ml, and 136.25 (16.57, 1553.25) ng/ml, respectively. Two consecutive post-treatment results were more minor and statistically significant than the previous results (P < 0.001). The patients' pain symptoms were significantly relieved after 125I brachytherapy (P < 0.001). The pain scores before 125I seed implantation and at 1, 3, and 5 months after the operation were 5.00 (4.00, 6.00), 3.00 (2.25, 4.00), 2.00 (2.00, 3.00), and 2.00 (1.00, 3.00), respectively. Conclusion: Most lesions treated with 125I seed implantation in RAIR-DTC patients showed shrinkage and improved pain symptoms. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT06362772.

[Molecular mimicry between human thyroid peroxidase, thyroglobulin, cosinophil peroxidase, IL-24 and microorganisms antigens]. / Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos.

OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.

OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.