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PURPOSE: This updated systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT for the detection of recurrent disease in patients with differentiated thyroid cancer (DTC) who have negative 131I whole body scintigraphy and increased antithyroglobulin antibodies (TgAb) levels. METHODS: The current systematic review was carried out following a preset protocol, and the "Preferred Reporting Items for a Systematic Review and Meta-Analysis" served as a guideline for its development and reporting. A comprehensive research of the PubMed/MEDLINE, Embase and Cochrane library databases was conducted until June 2024. RESULTS: Between 2002 and 2023, 13 studies (608 patients) published on this topic were selected. The pooled sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 2-[18F]FDG PET or PET/CT were 84% (95%CI: 78-87%), 82% (95%CI: 78-86%), 72% (95%CI: 67-76%), 90% (95%CI: 87-93%) and 83% (95%CI: 79%-86%) respectively. The pooled positive and negative likelihood ratios (LR+ and LR - ) and the diagnostic odds ratio (DOR) were 0.180 (95%CI: 0.128-0.253), 3.214 (95%CI: 2.357-4.383), and 17.863 (95%CI: 10.475-30.462), respectively. No statistically significant heterogeneity among the studies was found for all the metrics evaluated (I2 < 50%). CONCLUSIONS: 2-[18F]FDG PET/CT demonstrated a good diagnostic performance in patients with DTC and increased TgAb. Although more studies are warranted, the provided evidence-based data should support the integration of 2-[18F]FDG PET/CT in clinical and diagnostic guidelines on DTC patients with increased TgAb.

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OBJECTIVE: Ablation therapy is employed in low-risk differentiated thyroid cancer (DTC) cases to facilitate patient monitoring by reducing thyroglobulin (Tg) levels to measurable levels below after surgery by eliminating residual thyroid tissue. However, there is still uncertainty about the minimum activity dose required for effective ablation. Opting for low-dose [131I]-NaI for ablation offers several advantages for both patients and healthcare services. Particularly in this tumor group with a high life expectancy (approximately 90-95 % at 10 years), [131I]-NaI treatment should not pose a risk to the patient's post-treatment life and should not compromise their quality of life. However, there is a need for a well-defined identification of factors predicting successful ablation. METHODS: Clinical data, laboratory findings, and imaging tests of 287 patients with low-dose 1110 MBq (30 mCi) [131I]-NaI ablation therapy for DTC were retrospectively reviewed. Post-ablation imaging and laboratory findings categorized ablation success/failure. The successful ablation group was determined according to the excellent response criteria outlined in ATA criteria. Relationships between clinical, pathological findings, biochemical common variables, and treatment failure were analyzed. RESULTS: An excellent response was achieved in 77% of the entire group according to ATA criteria post-ablation. Male gender and high Tg levels on the day of ablation (Tg cut-off: 10 ng/mL and 5.35 ng/mL) were associated with unsuccessful ablation. CONCLUSIONS: Our results indicate that a 1110MBq (30mCi) ablation dose is sufficient to achieve an excellent response in most low-risk DTC cases 6-12 months later. When selecting the dose for ablation, besides the histological markers mentioned in guidelines and age, we observed that stimulated Tg values and gender may be important in predicting ablation success.

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In recent years, iodine deficiency-related diseases have been effectively controlled; the prevalence of excessive iodine-induced thyroid diseases has increased, such as hyperthyroidism. However, there are still several controversial outcomes regarding the relationship between excessive iodine intakes and hyperthyroidism. MicroRNAs (miRNAs) extensively participate in the progression of thyroid diseases; nevertheless, the relationship and mechanism between iodine exposure and miRNAs have not been explored in hyperthyroidism patients. In this study, a total of 308 pairs of hyperthyroidism patients and healthy controls were enrolled in. Logistic regression analysis showed that level of water iodine >100 µg/L was an independent risk factor for hyperthyroidism. Compared with the healthy control, the serum thyroglobulin (Tg) content and levels of interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly elevated in hyperthyroidism patients. Further, high-throughput miRNA sequencing was applied to find crucial miRNAs involved in the occurrence of hyperthyroidism related to excessive water iodine. Based on the fold change and Q value, miR-144-3p, miR-204-5p, miR-346, miR-23b-5p, and miR-193b-3p were selected for validation by qRT-PCR. Our results showed that miR-346 and miR-204-5p in the case group were significantly lower than those of the control group, and the similar results found under the level of water iodine >300 µg/L. Nonetheless, no significant difference was found at 10-100 µg/L level of water iodine. Furthermore, the ROC curve indicated that miR-346 and miR-204-5p had the ability to diagnose hyperthyroidism patients. Taken together, excessive water iodine may decrease the expression of miR-346 and miR-204-5p, which mediate the elevation of Tg and cytokines, ultimately making contribution to the development of hyperthyroidism.

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INTRODUCTION: Differentiated thyroid cancer (DTC), the most common endocrine malignancy is subdivided into papillary (the most common) and follicular type. Generally, DTC has a good prognosis with standard treatments such as surgery and, in some cases, radioactive iodine (RAI). Post-treatment follow-up includes thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) measurement and imaging to assess treatment success and detect recurrence. However, TgAb can interfere with Tg measurements, making it essential to measure TgAb at different times (months).  Aim of the study: The aim of this study was to evaluate the changes in TgAb level in DTC patients after thyroidectomy and its association with recurrence. METHODS: This was a retrospective cohort study done at the Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), Basrah, Iraq, for individuals diagnosed with DTC between 2008 and 2023. The data collected were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States). The categories were classified according to the TgAb level as: (i) elevated (>115 IU/ml) and (ii) normal (<115 IU/ml), where TgAb levels measured at 0-6 months, 6-12 months, 24-36 months, 36-48 months, and beyond 48 months. RESULTS: The mean age at diagnosis of the study population (n=108) was 40.15 years with a female-to-male ratio of 4:1. Among these individuals, 52.8% (n=57) were found to be obese. Total thyroidectomy was performed on 84.3% (n=91). Papillary thyroid cancer was diagnosed in 69.5% (n=75). TgAb levels were influenced by body mass index (BMI); higher BMI (>30kg/m2) was associated with less consistent TgAb normalization, particularly beyond 48 months (P = 0.04). The study found no significant differences in TgAb normalization based on gender, age, BMI, type of surgery, type of cancer, American Thyroid Association (ATA) risk of recurrence, or radioactive iodine (RAI) treatment. CONCLUSION:  Factors including gender, age, type of surgery, type of cancer, ATA risk of recurrence, and RAI treatment did not significantly affect TgAb normalization in DTC individuals over the study period. However, higher BMI is associated with less consistent TgAb normalization in the long term.

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BACKGROUND: Papillary thyroid carcinoma (PTC) occasionally invades the trachea and requires airway resection. Tracheal excision site recurrence (ESR) is a serious problem. We investigated predictors of ESR in patients with PTC who underwent airway resection for locally curative surgery. METHODS: We enrolled 149 patients with PTC who underwent airway resection (median age at the initial surgery: 67 years), including partial-thickness resection (n = 73) or full-thickness resection (n = 76), for grossly curative surgery. The median postoperative follow-up period was 93 months. RESULTS: To date, 11 patients (6.7%) underwent ESR: 6 underwent full-thickness resection and 5 underwent partial-thickness resection. The time to ESR ranged from 14 to 113 months (median: 57 months) after the initial surgery. None of the 11 ESR patients underwent adjuvant external beam radiotherapy (EBRT) and none of the 4 airway resection patients who underwent EBRT developed ESR. The 5- and 10-year ESR rates were 4.3% and 11.3%, respectively. In the multivariate analysis (forward-backward stepwise selection method), a Ki-67 labeling index (LI) ≥5% (p = 0.048) and the thyroglobulin doubling rate (Tg-DR) >0.33/year (p = 0.009) (for Tg-antibody negative cases) were independent predictors of ESR. Nine of the 11 patients underwent ESR resection and only one developed a second recurrence. CONCLUSIONS: A high Ki-67 LI was a static predictor, and high Tg-DR was a dynamic predictor, of ESR in patients with PTC following airway resection. In such patients, careful postoperative monitoring for ESR is necessary and adjuvant therapies, such as EBRT, may be considered.

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Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%-50% CD90-positive cells. When seeded onto 96-well Matrigel®-coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4-5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%-30%, 6K-12K cells per well, and 0.03-1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200 µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ∼0.7 µM and ∼0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p'1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization.

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Purpose: This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT). Materials and methods: All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients' disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients' ultimate disease outcomes. Results: A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg ≥20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion: In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators.

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Radioisótopos de Yodo , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Femenino , Masculino , Radioisótopos de Yodo/uso terapéutico , Adolescente , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Estudios Retrospectivos , Pronóstico , Niño , China/epidemiología , Estudios de Seguimiento , Resultado del Tratamiento , Tiroglobulina/sangre , Terapia Combinada

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CONTEXT: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management. OBJECTIVE: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone. DESIGN: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database. PATIENTS: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies. INTERVENTIONS: Serum Tg levels assessed at 1-year follow-up visit. MAIN OUTCOME MEASURE: Detection of structural disease within 5 years of follow-up. RESULTS: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease. CONCLUSIONS: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA.

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Background Despite the excellent prognosis of differentiated thyroid carcinoma, recurrence remains a major concern. However, the persistence of thyroid cancer post-thyroidectomy is not uncommon. We aimed to characterise patients who underwent re-operative surgery for differentiated thyroid carcinoma and analyse the percentage of re-operations that truly were for "recurrent" disease versus the management of persistent disease. Methods We conducted a retrospective review of the hospital database, analysing patients who visited the nuclear medicine department at Mediclinic City Hospital, a tertiary care hospital in Dubai, United Arab Emirates, between 2015 and 2022. The study included patients with differentiated thyroid carcinoma who underwent re-operations after total thyroidectomy. Recurrence was defined as the development of disease after a patient had undetectable thyroglobulin and negative radiological scans within one year of the first surgery. Cases were categorised as "recurrent", "persistent", or "unable to classify" in the event of missing data. Results Out of 836 patients diagnosed with differentiated thyroid carcinoma who visited the nuclear medicine department, 71 underwent re-operations. The mean age of these patients was 44.4 years (CI 41.7-47.0), of whom 78.9% were females. Almost half (46.5%) underwent re-operations within the first year, and 98.6% were diagnosed with papillary thyroid carcinoma. We were able to classify 63.4% of cases (n=45) as persistent disease, while 24 cases were categorised as "unable to classify". Only two cases met the criteria for recurrent disease. Conclusion The majority of cases previously classified as "recurrent" in differentiated thyroid carcinoma were found to be a persistent disease, possibly indicating inadequate therapy. Further research may be required to explore the reasons behind this eye-opening rate of disease persistence. This highlights an area for improvement in the management and future outcomes of differentiated thyroid carcinoma patients.

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Many cellular processes are governed by protein-protein interactions that require tight spatial and temporal regulation. Accordingly, it is necessary to understand the dynamics of these interactions to fully comprehend and elucidate cellular processes and pathological disease states. To map de novo protein-protein interactions with time resolution at an organelle-wide scale, we developed a quantitative mass spectrometry method, time-resolved interactome profiling (TRIP). We apply TRIP to elucidate aberrant protein interaction dynamics that lead to the protein misfolding disease congenital hypothyroidism. We deconvolute altered temporal interactions of the thyroid hormone precursor thyroglobulin with pathways implicated in hypothyroidism pathophysiology, such as Hsp70-/90-assisted folding, disulfide/redox processing, and N-glycosylation. Functional siRNA screening identified VCP and TEX264 as key protein degradation components whose inhibition selectively rescues mutant prohormone secretion. Ultimately, our results provide novel insight into the temporal coordination of protein homeostasis, and our TRIP method should find broad applications in investigating protein-folding diseases and cellular processes.

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Pliegue de Proteína , Humanos , Hipotiroidismo Congénito/metabolismo , Hipotiroidismo Congénito/genética , Proteína que Contiene Valosina/metabolismo , Proteína que Contiene Valosina/genética , Tiroglobulina/metabolismo , Espectrometría de Masas/métodos , Mapas de Interacción de Proteínas , Mapeo de Interacción de Proteínas/métodos , Proteolisis , Proteostasis , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/genética

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Objective: To identify the relationship between thyroid autoimmunity and antinuclear antibody (ANA) prevalence in Chinese pregnant women. Methods: The study involved 1923 first-trimester women who were measured for thyroid stimulating hormone (TSH) level, thyroid autoantibodies (thyroperoxidase antibody [TPOAb] and thyroglobulin antibody [TgAb]) and ANA titer. Social demographic data were collected through standardized questionnaires. Results: In this study, 23.3% of pregnant women tested positive for TPOAb and 9.9% tested positive for TgAb. Women with a positive ANA were more likely to be TPOAb-positive or TgAb-positive than women with a negative ANA (adjusted odds ratio [AOR] 1.96, 95% confidence interval [CI] 1.47-2.62 for TPOAb [+]; AOR 3.12, 95% CI 2.18-4.48 for TgAb[+]). In addition, ANA titers were closely associated with thyroid autoimmunity. Women with an ANA titer of >1:320 had a significant higher risk of being TPOAb positive or TgAb positive (AOR 4.49, 95% CI 1.48-13.66 for TPOAb [+]; AOR 5.51, 95% CI 1.65-18.49 for TgAb [+]). The higher the ANA titer, the greater the risk of developing thyroid autoimmunity, especially for those with a high ANA titer. Conclusions: ANA positivity is strongly correlated with thyroid autoimmunity. Further study is warranted to clarify the causal relationship between thyroid autoimmunity and ANA in pregnant women.This research is essential to evaluate and predict the risk of co-existing autoimmune disorders,leading to improved care for pregnancy and neonatal health.

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Anticuerpos Antinucleares , Autoanticuerpos , Autoinmunidad , Humanos , Femenino , Embarazo , Estudios Transversales , Adulto , China/epidemiología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Prevalencia , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/sangre , Adulto Joven , Glándula Tiroides/inmunología

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Subclinical hypothyroidism and thyroid autoimmunity in pregnancy are common conditions. They are both associated with adverse maternal and offspring outcomes. Women with thyroid autoimmunity should be monitored with regular thyroid function tests preconception and during gestation to identify women who develop hypothyroidism. The effectiveness of thyroid hormone treatment in reducing adverse outcomes in pregnancy has been studied in a number of randomized controlled trials. Current evidence shows obstetrical benefits of levothyroxine treatment in pregnant women with a thyroid-stimulating hormone level greater than 4 mU/L.

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Hipotiroidismo , Complicaciones del Embarazo , Humanos , Embarazo , Femenino , Hipotiroidismo/inmunología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/complicaciones , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/tratamiento farmacológico , Tiroxina/uso terapéutico , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/tratamiento farmacológico , Autoinmunidad/efectos de los fármacos

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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.

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Hipotiroidismo Congénito , Tiroglobulina , Humanos , Tiroglobulina/genética , Femenino , Masculino , Hipotiroidismo Congénito/genética , Niño , Preescolar , Secuenciación de Nucleótidos de Alto Rendimiento , Fenotipo , Lactante , Disgenesias Tiroideas/genética , Mutación , Adolescente , Adulto , Recién Nacido

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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.

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Radioisótopos de Yodo , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/sangre , Adulto , Cáncer Papilar Tiroideo/radioterapia , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/sangre , Estudios de Seguimiento , Pronóstico , Anciano , Tiroglobulina/sangre , Resultado del Tratamiento , Adulto Joven , Factores de Riesgo , Carcinoma Papilar/radioterapia , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía

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BACKGROUND: Various prognostic factors are expected to refine the American Thyroid Association (ATA) recurrence risk stratification for patients with papillary thyroid cancer (PTC). However, it remains unclear to what extent integrating these factors improves patient treatment decision-making. METHODS: We developed two predictive models for structural incomplete response (SIR) at the one-year follow-up visit, based on comprehensive clinical data from a retrospective cohort of 2539 patients. Model 1 included the recurrence risk stratification and lymph node features (i.e., number and ratio of metastatic lymph nodes, N stage). Model 2 further incorporated preablation stimulated thyroglobulin (s-Tg). An independent cohort of 746 patients was used for validation analysis. We assessed the models' predictive performance compared to the recurrence risk stratification using the integrated discrimination improvement (IDI) and the continuous net reclassification improvement (NRI). The clinical utility of the models was evaluated using decision curve analysis. RESULTS: Both Model 1 and Model 2 outperformed the recurrence risk stratification in predicting SIR, with improved correct classification rates (Model 1: IDI=0.02, event NRI=42.31%; Model 2: IDI=0.07, event NRI=53.54%). The decision curves indicated that both models provided greater benefits over the risk stratification system in clinical decision-making. In the validation set, Model 2 maintained similar performance while Model 1 did not significantly improve correct reclassification. CONCLUSION: The inclusion of lymph node features and s-Tg showed potential to enhance the predictive accuracy and clinical utility of the existing risk stratification system for PTC patients.

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Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients.

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BACKGROUND: Thyroid cancer has an overall favorable prognosis, but no pre-operative biochemical marker has been shown to distinguish between low and high-risk disease or predict response to therapy. METHODS: We retrospectively reviewed 162 patients that underwent thyroid surgery for thyroid cancer between 2006 and 2022 in whom a pre-operative thyroglobulin level (Tg) was measured. We subdivided patients into low, intermediate and high-risk thyroid cancer and based on their response to therapy per ATA guidelines. RESULTS: We showed that as pre-operative Tg level increased, patients were more likely to have high-risk disease (p â€‹< â€‹0.01). We found a linear association between the primary tumor size and high-risk histology with pre-operative Tg (p â€‹< â€‹0.01). Pre-operative Tg level was significantly associated with response to therapy following initial surgical management. Specifically, as pre-operative Tg increases, patients were less likely to achieve an excellent response (p â€‹< â€‹0.01). CONCLUSIONS: Our retrospective analysis demonstrated that pre-operative Tg is significantly associated with ATA structural risk of recurrence and response to therapy and may have the potential to guide initial therapy and follow-up management.

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Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease in which the immune system attacks the myelin sheath of the central nervous system (CNS). It has been proposed that autoimmune conditions may occur together and an individual's immune system may attack more than one system. Autoimmune thyroid disease is one of the most common comorbidities along with MS. Since thyroid hormones are crucial for normal brain function and remyelination, we aimed to determine the prevalence of thyroid dysfunction in a group of MS patients compared with healthy controls. Methods: This cross-sectional study was conducted in medical clinics affiliated to Shiraz University of Medical Sciences, South of Iran. To prevent the effects of MS modifying drugs on thyroid function, we examined 73 newly diagnosed MS patients, which had not been treated yet, compared to 72 healthy individuals. Results: After measurement of the serum level of TSH, Anti TPO-Ab, and Anti TG-Ab, we found a significantly higher prevalence rate of abnormal TSH levels (high or low) in the MS group (p = 0.02). We also found a higher frequency of thyroid dysfunction in the female MS group (p = 0.01). However, there was no significant difference in the two other anti-thyroid antibodies among the groups. Our results demonstrate a significant and positive linear relationship between age and TSH levels (R = 0.402; p < 0.001) and also age and Anti TPO-Ab levels (R = 0.397; p < 0.001) among the MS population. Conclusion: We found a higher prevalence of TSH alteration among the MS population. Anti TPO-Ab and Anti TG-Ab levels did not differ among groups. These findings suggest that MS patients might be at an increased risk for thyroid dysfunction. However, further studies are required to determine the underlying cause. The linear relationship between age and TSH and Anti TPO-Ab levels in MS patients suggest that there is an association between TSH dysfunction and age.

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Malignant struma ovarii is an exceedingly rare pathology with a paucity of established criteria regarding management and surveillance with recommendations largely based on case reports and retrospective data. Many authors have supported stratification of malignant struma ovarii into low vs high-risk disease with more conservative management reserved for those deemed low-risk. Here we present a unique case of recurrent metastatic malignant struma ovarii after surveillance was undertaken in the setting of initially low-risk disease.

RESUMEN

Iodine deficiency results in elevated thyroglobulin (Tg) concentrations, with high iodine Tg being more immunogenic than low iodine Tg. The study investigated the correlation between serum iodine concentration and thyroglobulin autoantibody (TgAb) levels across diverse iodine nutritional statuses as determined by urine iodine concentration (UIC). Demographic information was collected from 1,482 participants through a questionnaire. Blood and spot urine were collected to measure thyroid-stimulating hormone (TSH), TgAb, thyroid anti-peroxidase antibody (TPOAb), serum iodine (SIC), serum non-protein-bound iodine (snPBI), urine iodine (UIC), creatinine (UCr). The median UIC and SIC were 146.5 µg/L and 74.9 µg/L, respectively. A linear relationship was observed between SIC, snPBI, and serum-protein-bound iodine (sPBI) (P < 0.001). The 90% reference intervals for SIC, snPBI, and sPBI were 50.7-120.7 µg/L, 21.9-52.9 µg/L, and 19.7-77.9 µg/L, respectively. The prevalence of elevated TgAb levels was significantly higher in women than in men (P < 0.001). Both low and high levels of snPBI and sPBI were associated with an increased risk of elevated TgAb levels. In women, the risk of positive TgAb in the group below the reference value of snPBI (OR = 2.079, 95%CI: 1.166, 3.705) and sPBI (OR = 2.578, 95%CI: 1.419, 4.684) was higher. In men, the risk of positive TgAb in the group below the reference value of SIC was higher (OR = 3.395, 95%CI: 1.286, 8.962). Iodine might exert an influence on TgAb levels through its binding to proteins, primarily Tg, thereby altering the iodine content of Tg. The interplay of gender factors further enhanced the risk of TgAb emergence.