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.

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.

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.

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.

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.

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.

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 meta-analysis of unilateral axillary approach for robotic surgery compared with open surgery for differentiated thyroid carcinoma.

OBJECTIVE: The Da Vinci Robot is the most advanced micro-control system in endoscopic surgical instruments and has gained a lot of valuable experience today. However, the technical feasibility and oncological safety of the robot over open surgery are still uncertain. This work is to systematically evaluate the efficacy of the unilateral axillary approach for robotic surgery compared to open surgery for differentiated thyroid carcinoma. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were utilized to search for relevant literatures of robotic thyroid surgery using unilateral axillary approach compared to open thyroid surgery, and a meta-analysis was performed using RevMan software version 5.3. Statistical analysis was performed through Mantle-Haenszel and inverse variance methods. RESULTS: Twelve studies with a total of 2660 patients were included in the meta-analysis. The results showed that compared with the open group, the robotic group had a longer total thyroidectomy time, shorter hospital stay, less intraoperative bleeding, more postoperative drainage, fewer retrieved central lymph nodes, and higher cosmetic satisfaction (all P < 0.05). In contrast, temporary and permanent laryngeal recurrent nerve injury, temporary and permanent hypoparathyroidism or hypocalcemia, brachial plexus nerve injury, number of retrieved central lymph nodes, number of retrieved lymph nodes in the lateral cervical region, number of lymph node metastases in the lateral cervical region, hematoma, seroma, lymphatic leak, stimulated thyroglobulin (sTg) and unstimulated thyroglobulin (uTg), and the number and recurrence rate of patients with sTg <1ng/ml were not statistically different between the two groups (P > 0.05). CONCLUSIONS: The unilateral axillary approach for robotic thyroid surgery may achieve outcomes similar to those of open surgery. Further validation is required in a prospective randomized controlled trial.

Predictors of recurrence after total thyroidectomy in 1,611 patients with papillary thyroid carcinoma: postoperative stimulated serum thyroglobulin and ATA initial and dynamic risk assessment.

Objective: Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). Subjects and methods: We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. Results: After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-riskto high-risk patients with postoperative s-Tg > 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. Conclusion: The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based ondynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.

[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.

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.

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.

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.

A Flexible Mouse Model of Autoimmune Thyroiditis Induced by Immunization with an Adenovirus Containing Full-Length Thyroglobulin cDNA.

The main challenge in the "post-GWAS" era is to determine the functional meaning of genetic variants and their contribution to disease pathogenesis. Development of suitable mouse models is critical because disease susceptibility is triggered by complex interactions between genetic, epigenetic, and environmental factors that cannot be modeled by in vitro models. Thyroglobulin (TG) is a key gene for autoimmune thyroid disease (AITD) and several single nucleotide polymorphisms (SNPs) in the TG coding region have been associated with AITD. The classical model of experimental autoimmune thyroiditis (EAT), based on immunization of genetically susceptible mouse strains with purified TG protein in adjuvant, does not allow testing the impact of TG sequence variants on the development of autoimmune thyroiditis. Here we describe a protocol for the induction of EAT by immunization of mice susceptible to thyroiditis with an adenovirus vector carrying full-length human TG cDNA (Ad-TG EAT). We also provide support protocols for evaluation of autoimmune thyroiditis including serological assessment of TG antibodies, in vitro splenocyte proliferation assay and cytokines secretion, thyroid histology, and evaluation of thyroid lymphocytic infiltration by immunostaining. This protocol for EAT induction allows manipulation of the TG cDNA to introduce variants associated with AITD, enabling the testing of the functional effects of susceptible variants and their haplotypes on the immunogenicity of TG. Furthermore, the Ad-TG EAT mouse model is a valuable model for studying the interactions of the TG variants with non-genetic factors influencing AITD development (e.g., cytokines, iodine exposure) or with variants of other susceptible genes (e.g., HLA-DRß1). © 2024 Wiley Periodicals LLC. Basic Protocol: Development of a mouse model of autoimmune thyroiditis induced by immunization with adenovirus containing full-length thyroglobulin cDNA Support Protocol 1: Splenocytes isolation Support Protocol 2: T cell stimulation and carboxyfluorescein diacetate succinimidyl ester (CFSE) based cell proliferation assay Support Protocol 3: Cytokine assays: measuring levels of interferon gamma (IFNγ) and interleukins IL-2, IL-4, and IL-10 in splenocyte supernatants Support Protocol 4: Evaluating thyroid histology and infiltration with immune cells: hematoxylin-eosin staining of mice thyroid glands Support Protocol 5: Immunohistochemistry of thyroid tissues: Immunofluorescence protocol of paraffin-embedded thyroid sections Support Protocol 6: Anti-thyroglobulin antibody measurement in mice sera by enzyme-linked immunosorbent assay (ELISA).

Platelet-rich plasma efficacy in alopecia areata patients with normal and elevated levels of antibodies against thyroglobulin and thyroid peroxidase.

AIM: To evaluate and compare the efficacy of platelet-rich plasma (PRP) therapy in alopecia areata (AA) patients with normal and with elevated levels of anti-thyroglobulin antibodies and/or anti-thyroid peroxidase antibodies.

Prospective evaluation of 68 Ga-NODAGA-RGD PET-CT in patients of carcinoma thyroid with thyroglobulin elevated negative radioiodine scintigraphy (TENIS) with a head-to-head comparison with FDG-PET/CT.

BACKGROUND AND AIM: This study aimed to examine the expression of RGD binding integrins in patients of elevated serum thyroglobulin (Tg) level with negative radioiodine scintigraphy (TENIS) employing 68 Ga-NODAGA-RGD PET-CT. MATERIAL AND METHODS: This was a prospective study involving 30 proven cases of TENIS with histopathological diagnosis of differentiated thyroid carcinoma post-surgery. In addition to observing the lesional concentration on 68 Ga-NODAGA-RGD PET-CT, a 4-point visual grading system (grade I-IV), was undertaken to estimate the degree of radiotracer avidity, for potential of theranostics. RESULTS: On 18 F-FDG-PET/CT, the uptake was seen in 182 lesions out of a total of 200 (91%). 68 Ga-NODAGA-RGD PET-CT showed expression in a total of 110/200 (55%) lesions. On patient-specific analysis, 68 Ga-NODAGA-RGD PET-CT was positive for the disease in 21/30 patients (70%) and negative in 9/30 (30%) patients. The overall patient-specific sensitivity and specificity of 68 Ga-NODAGA-RGDPET-CT were 75% and 100%, respectively. 18 F-FDG PET-CT was positive for the disease in 26/30 patients (86.66%) and negative in 4/30 (13.33%) patients. The overall patient-specific sensitivity and specificity of 18 F-FDG-PET/CT were 92.86% and 100%, respectively. The 4-point visual grading system revealed 14/200 (7%) lesions demonstrating Grade I uptake, 49/200 (24.5%) lesions grade II uptake, 17/200 (8.5%) lesions grade III uptake and 40/200 (20%) lesions grade IV uptake. CONCLUSION: The results suggested that RGD-binding integrin is expressed in a sizeable fraction of metastatic lesions of TENIS cases, albeit demonstrating a varying degree of uptake. Out of the soft tissue, lung, and bone lesions, metastatic bone lesions showed more RGD affinity than other sites. The patients with substantial RGD uptake on a 4-point visual grading system may be potential targets for RGD-based therapy.

Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer.

OBJECTIVE: We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. METHODS: Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. RESULTS: Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. CONCLUSION: Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.

False diagnosis of recurrent thyroid carcinoma: the importance of testing for heterophile antibodies.

Thyroglobulin (Tg) levels are important to predict recurrence in differentiated thyroid cancer patients.However, false-positive results can hence the request of unnecessary tests and treatments. We reported two cases of interference in thyroglobulin measurement and the workup to investigate them. Both patients achieved an excellent response to therapy after total thyroidectomy and one patient had also received radioiodine treatment. During the follow-up, Tg levels increased and there was no evidence of recurrent disease in the imaging studies. The Tg levels by the Access platform were positive but the results by Elecsys platform and LC-MS/MS were undetectable, leading to the hypothesis of heterophile antibodies (HAbs) interference. The possibility of HAbs interference must be considered when the Tg levels do not fit in the clinical picture. The measurement of Tg by another immunoassay or by LC-MS/MS may be useful in these situations.