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Differentiated thyroid carcinoma is the most common endocrinological malignancy with an increasing incidence over the last 30 years, with women being more frequently affected. In indicated cases, total thyroidectomy followed by adjuvant radioiodine administration is performed, despite current trends towards less aggressive treatment. We would like to investigate the possible adverse effects of radioiodine (RAI) on ovarian function using a simple serum biomarker. Anti-Müllerian hormone (AMH) appears to be the best endocrine marker for assessing physiological age-related oocyte loss for healthy women. The aim of our ongoing prospective study is to determine serum AMH to estimate ovarian reserve for premenopausal women treated with RAI. Over the course of one year, 33 serum samples from women with thyroid cancer and 3 serum samples from healthy women were examined. AMH levels were compared before radioiodine treatment and at regular intervals after treatment. Mean of the AMH level was 5.4 ng/ml (n=33) prior to RAI. The average level of AMH decreased to 1.8 ng/ml in 4-6 months after treatment. In 22.2 % of patients AMH dropped to 0 ng/ml from a non-zero value. Thereafter, we observed an increase in AMH, the average value was 2.7 ng/ml in 8-12 months. We demonstrated a significant decrease in AMH shortly after radioiodine treatment and a subsequent trend of increase at one year after treatment. Consequently, predicting the adverse effects of radioiodine by assessing a serum biomarker could help to select an appropriate treatment strategy for young women planning pregnancy.

Polybrominated diphenyl ethers (PBDEs), a category of persistent organic pollutants (POPs), are ubiquitous in the environment and have been reported to have endocrine-disrupting and tumor-promoting activities. However, the evidence for the correlation between plasma PBDEs levels, thyroid homeostasis and thyroid carcinoma in humans remains limited. Herein, we analyzed eight PBDE congeners in 53 patients undergoing thyroid surgery. BDE-209 was identified as the most abundant PBDE congener in plasma (median, 11.36 ng/g lipid). BDE-100 concentration was positively associated with free triiodothyronine (FT3), indicating a potential interference with thyroid function. Point-biserial correlation analysis revealed positive associations between certain plasma PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-154) and aggressive pathological parameters. There was no significant correlation between PBDEs and BRAF or RAS mutations in PTC patients, indicating that PBDEs may not directly promote the initiation and progression of thyroid cancer through these genetic mutations. It implies the complexity of the relationship between PBDEs exposure and thyroid cancer development. Although not statistically significant, Bayesian kernel-machine regression (BKMR) analysis of single-exposure effects model found that BDE-47 and BDE-99 were positively associated with the risk of malignant neoplasms. The present study not only contributes to the growing evidence regarding the impact of PBDEs on thyroid function but also provides new insights into the association between exposure to certain PBDE congeners and the aggressive pathological parameters of thyroid cancer. Large-scale prospective studies are still needed to support our findings., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: TENIS syndrome is characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin (Tg) levels, and negative whole-body 131 I scans. In such patients, somatostatin receptor imaging with 68 Ga-DOTATATE PET/CT (somatostatin receptor [SSR] PET/CT) and 18 F-FDG PET/CT (FDG PET/CT) can identify metastases and were compared under 2 conditions: elevated (eTSH) and suppressed (sTSH) TSH serum levels. Potential candidates for peptide receptor radionuclide therapy (PRRNT) were identified in 15 patients prospectively enrolled. All patients underwent 4 examinations. Images were blindly evaluated for differences in SUV max values and lesion detectability. Reference standard consisted of neck ultrasound, CT, MRI, PET/CT, biopsy, and follow-up. Three patients were received PRRNT., Results: sTSH SSR PET/CT detected a greater number of cervical ( P = 0.0253 and P = 0.0176) and distant LNs ( P = 0.0253 and P = 0.0391) when compared with sTSH FDG PET/CT, respectively, in a per-patient and on a per-lesion based analysis. Likewise, eTSH SSR PET/CT detected a greater number of patients with local recurrences ( P = 0.0455) and distant LN metastases ( P = 0.0143). Per-lesion analysis revealed greater number of cervical and distant LNs ( P = 0.0337 and P = 0.0039, respectively) when compared with eTSH FDG PET/CT. There was no difference in detection of distant metastases by both tracers for lung and bone metastases (κ = 1). Both skeletal and pulmonary lesions were also detected by conventional CT part of FDG or DOTATATE PET/CT scans. TSH stimulation had no additional value in a per-patient analysis for both FDG and DOTATATE PET scans (κ varying from 0.6087 to 1). However, TSH stimulation led to more lesion identifications in DOTATATE PET/CT; most of those metastases were not confirmed by the reference standard leading to a decrease in specificity (84% vs 74%). One of 3 patients submitted to 3 cycles of PRRNT presented with a visual partial response, a 20% reduction in quantitative analyses, and stable disease regarding Tg and TgAb levels., Conclusions: Patients with TENIS syndrome can be imaged with SSR PET/CT as well as FDG PET/CT with high overall accuracy regardless of TSH levels (86% to 92% and 92% to 85%, respectively, with eTSH and sTSH). SSR PET/CT detected a greater number of locoregional and distant LN metastases than FDG PET/CT with both sTSH and eTSH. One of 3 patients submitted to PRRNT presented a partial response to treatment. Our findings may impact in patient restaging, management, and theranostics strategies with radiolabeled somatostatin analogs., Competing Interests: Conflicts of interest and sources of funding: This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. The authors declare no financial (or other) conflict of interest relating to Employment or Leadership Position, Consultant or Advisory, Stock Ownership, Honoraria, Expert Testimony, Patents, Royalties, Licenses, or other Remuneration. D.E.Z.-W. had a National Council of Technological and Scientific Development Scholarship (CNPq) (303068/2021-3), and L.S.A. had a CAPES-Print Funding for doctorate Scholarship (CAPES) (88887.716546/2022-00)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2024 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Detectable, and especially rising postthyroidectomy serum calcitonin and carcinoembryonic antigen levels, as per American Thyroid Association guidelines, indicate potential disease presence, requiring frequent calcitonin measurement or imaging for early detection of persistent or recurrent medullary thyroid carcinoma. Thus, defining the clinical cutoff value of detection of calcitonin assays relative to imaging and clinical status is crucial for patient care. This study aimed to evaluate postoperative calcitonin levels using the new Siemens Atellica assay system to determine the most appropriate levels for clinical decision-making., Methods: A retrospective analysis was conducted using Siemens Atellica for calcitonin testing on 56 samples from 40 patients between September 27, 2022 and August 11, 2023. Only calcitonin results performed at least 3 months post-total thyroidectomy were included. Imaging studies, within 6 months of the calcitonin report, were assessed. Carcinoembryonic antigen results were also reviewed., Results: Precision analysis at 2.94 and 5.24 pg/mL revealed coefficients of variation at 16.49% and 8.87%, respectively. For the evidence of post-total thyroidectomy persistent or recurrent medullary thyroid carcinoma confirmed by imaging, using a 1.89 pg/mL cutoff for calcitonin yielded 43% sensitivity and 67% specificity. Using a 5.00 pg/mL cutoff resulted in 0% sensitivity and 100% specificity., Conclusions: Our findings indicate the potential suitability of a 5 pg/mL calcitonin cutoff on the Siemens Atellica platform for evaluating tumor persistence or recurrence in post-thyroidectomy patients in our institution. However, individual laboratories should establish their own clinical cutoff value when evaluating calcitonin levels for monitoring tumor recurrence post-thyroidectomy., Competing Interests: Disclosure The authors declare that the article does not contain previously published material, and is not under consideration for publication elsewhere. Each author has made an important scientific contribution to the study and is thoroughly familiar with the primary data. All the authors listed have read the complete manuscript and have approved submission of the paper. The manuscript is a truthful original work without fabrication, fraud or plagiarism. The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions., Methods: Cross sectional, single center study, involving all consecutive patients (N = 3015) who were submitted to thyroid surgery between 2001-2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed., Results: No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99-2.28) and certain (OR: 1.74, 95% CI: 1.09-2.78) thyroid autoimmunity (p = 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08-1.45, p = 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24-0.67, p < 0.001). The most frequent genetic alteration was BRAF V600E mutation, found in 56.3% of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAF V600E mutation was observed., Conclusions: Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Conceptually, thyroid tumor desmoplasia may be better suited for excluding node metastases in sporadic MTC than preoperative serum calcitonin levels., Methods: This analysis included 181 patients with unilateral sporadic MTC graded on the 7-grade desmoplasia scale after thyroidectomy and neck dissection., Results: When thyroid tumor desmoplasia reached 1% and ≥50%, node metastases increased from 0% to 7% (median of 0 metastases) and 83% (median of 7.5 metastases), microscopic lymphatic invasion from 0% to 3% and 35%, extrathyroid extension from 0% to 5% and 22%, and extranodal growth from 0% to 0% and 44%, whereas biochemical cure declined from 100% to 95% and 25%. Thyroid tumor diameters and basal calcitonin overlapped widely among the seven desmoplasia groups, precluding differentiation by thyroid tumor size or serum calcitonin levels., Conclusions: Thyroid tumor desmoplasia, unlike serum calcitonin levels, discriminates extremely well between node-negative and node-positive sporadic MTC, opening new avenues for precision surgery., (© 2024 Wiley Periodicals LLC.)

Background: The treatment for papillary thyroid microcarcinoma (PTMC) is controversial. Central lymph node metastasis (CLNM) is one of the main predictors of recurrence and survival, accurate preoperative identification of CLNM is essential for surgical protocol establishment for PTMC. The objective of this study was to establish a nomogram to predict the possibility of CLNM in PTMC patients., Methods: A total of 3023 PTMC patients were randomly divided into two groups by a ratio of 7 to 3, the training group (n = 2116) and validation group (n = 907). The LASSO regression model and multivariate logistic regression analysis were performed to examine risk factors associated with CLNM. A nomogram for predicting CLNM was established and internally validated. Meanwhile, we follow-up the serum thyroid function FT3, FT4, TSH, Tg, TGAb and TPOAb in 789 PTMC patients for 4 years after surgery and compared the differences between the CLNM (+) and CLNM (-) groups, respectively., Results: The LASSO regression model and multivariate logistic regression analysis showed that younger age, lower BMI, being male, location in the lower pole, calcification, 1 ≥ diameter ≥ 0.5 cm, multifocality lesions, extra thyroidal extension (ETE), enlargement of central lymph node (ECLN), lateral lymph node metastasis (LLNM) and higher carcinoembryonic antigen were the ultimate risk factors for determining CLNM. A nomogram for predicting CLNM was constructed based on the influencing factors and internally validated. By establishing the prediction model, the AUC of CLNM in the training and validation groups were 0.73 (95% CI, 0.70-0.76) and 0.75 (95% CI, 0.71-0.79) respectively. Results of the DCA showed that the model is clinically useful when deciding on intervention in the most range of the threshold probability. A 4-year follow-up of thyroid function showed that FT3 and FT4 remained at stable levels after 3 months postoperative and were higher in the CLNM (+) group than in the CLNM (-) group. Hypothyroidism appeared predominantly within 3 months after surgery. The overall incidence of the CLNM (+) group and CLNM (-) groups were 16.46% and 12.04%, respectively., Conclusion: The nomogram model constructed in this study has a good predictive effect on CLNM in PTMC patients and provides a reasonable reference for clinical treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Lou, Li, Li, Ma and Wang.)

Purpose: Pregnant women with a diagnosis of differentiated thyroid cancer (DTC) were potentially high-risk but largely ignored study population. We aimed to explore whether gestational thyrotropin levels were associated with progression of DTC., Methods: We conducted a retrospective cohort study at Peking University Third Hospital in Beijing, China from January 2012 to December 2022. We included pregnant women with a pre-pregnancy DTC managed by active surveillance (under-surveillance DTC) or surgical treatment (after-surgery DTC). Dynamic changes of gestational thyrotropin levels across multiple time points were characterized by both statistical (average level, change instability, longitudinal trajectory) and clinical (thyroid dysfunction, thyrotropin suppression, and achievement of thyrotropin suppression target) indicators. Outcomes were clinician-validated progression of DTC, measured separately for patients under surveillance (tumor enlargement or lymph node metastasis) and those after surgery (≥ 3 mm growth in the size of existing metastatic foci, development of new lymph node metastases, ≥ 2 mm growth in the size of existing cancer foci in the contralateral thyroid, or biochemical progression)., Results: Among 43 and 118 patients with under-surveillance and after-surgery DTC, we observed no evidence of associations between any of the quantitative or clinical indicators of gestational thyrotropin levels and progression-free survival, after a median of 2.63 (IQR: 0.90-4.73) and 4.22 (2.53-6.02) year follow-up, respectively (all P values > 0.05)., Conclusions: Gestational thyrotropin levels appeared to play a minor role in the progression of under-surveillance or after-surgery DTC. Clinicians might focus on the risk of adverse pregnancy outcomes when optimizing thyrotropin levels for pregnant women with a diagnosis of DTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Fu, Xiao, Mei, Zhang, Zhang, Chen, Shan, Sun, Song, Yuan and Liu.)

Fine-needle aspiration cytology (FNAC), used in suspicious cervical lymph nodes of unknown origin is frequently inconclusive and prone to false negatives. In order to evaluate the usefulness of measuring thyroglobulin in the washing with saline solution of the puncture needle for the diagnosis of metastasis of papillary carcinoma of the thyroid, an optimal thyroglobulin cutting point has to be calculated, being positive or negative depending on whether the thyroglobulin levels are higher or lower than the cutting point. We have retrospectively studied 33 patients (19 women and 14 men) with an average age of 49.3 years, with papillary carcinoma of the thyroid and suspected lymph node metastasis. Of them 16 (47.1%) had a positive FNAC. To determine thyroglobulin predictive capacity with regards to the metastasis of papillary carcinoma of the thyroid a ROC analysis was carried out with an under curve area UCA: 0.987 (CI 95%: 0.808-1.000) obtaining, using Youden's J statistic, 0.4 ng/ml as the thyroglobulin cutting point with best predictive capacity. The study of the relationship between thyroglobulin and the preservation/non-preservation of the thyroid showed statistically significant differences (P=.023). Our results validate 0.4 ng/ml of thyroglobulin as an optimal cutting point of the presence of metastasis of papillary carcinoma of the thyroid in lymph nodes. When reviewing the bibliography, a great diversity of cutting points may be found, which is explained mainly by the great inter-observer and inter-assay variability. That is why we recommend calculating each laboratory's own optimal cutting point; and determine in subsequent studies two cutting points depending on whether or not thyroid is preserved., (Copyright © 2024 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Purpose: The aim of this study was evaluate biochemical incomplete response (BIR) in Middle Eastern differentiated thyroid cancer (DTC), identify factors that could predict BIR before radioactive iodine (RAI) ablation and to investigate the long-term clinical outcome of DTC patient exhibiting BIR to initial therapy., Methods: We retrospectively evaluated 1286 DTCs from Middle Eastern ethnicity who underwent total thyroidectomy and RAI therapy. Demograpic and clinico-pathological factors predicting BIR were evaluated. The outcome of these patients was analyzed using primary outcome of structural disease and disease-free survival (DFS)., Results: With a median follow-up of 10 years, 266 (20.7%) patients had BIR. High pre-ablation stimulated thyroglobulin (presTg), presence of lymph node metastasis, male gender and delayed initial RAI therapy (≥3 months) after thyroidectomy were significant independent predictors of BIR. Upon evaluating long-term clinical outcomes in 266 patients with BIR, we found 36.8% of patients developed structural disease. Male sex (OR = 1.56; 95% CI = 1.05-2.30; p = 0.0272) and increasing Tg after initial therapy (OR = 4.25; 95% CI = 1.93-10.82; p = 0.0001) were independent risk factors for structural disease in patients with BIR. DFS was significantly worse if both these risk factors existed concomitantly (p < 0.0001)., Conclusion: To achieve the fair efficacy of RAI therapy, early prediction of BIR before RAI ablation is desirable. Our finding of the clinico-pathological factors (high presTg level, LNM, delayed RAI therapy and male gender) could serve as easy and robust early predictors of BIR. In addition, DTC patients exhibiting BIR had a high risk of structural disease and hence personalized management approach would be preferable for BIR patients to ensure best clinical outcome., (© 2024. The Author(s).)

Background: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms., Methods: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis., Results: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (P trend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (P trend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer., Conclusions: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To investigate the clinical value of blood routine derivative biomarkers and thyroid function biomarkers in differentiating different thyroid diseases., Methods: The differences of blood routine derived indexes neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), platelet-large cell rate (P-LCR) and thyroid function indexes between benign and malignant thyroid diseases were compared, and the differences of each index between different benign thyroid diseases were further compared. Univariate regression analysis model was used to analyze the clinical value of various indexes. Receiver operating characteristic curve (ROC) was used to calculate the area under the curve (AUC)., Results: There were statistically significant differences in PLR, NLR and P-LCR between patients with benign and malignant thyroid diseases (P < 0.05 for each). The results of univariate logistic regression analysis showed that P < 0.05 for all indicators except LMR, when PLR and NLR value increased by 1, the risk of thyroid malignancy decreased by 1 % and 21 %, when P-LCR value increased by 1, the risk of thyroid malignancy increased by 4 %., Conclusions: PLR, NLR and P-LCR are helpful to distinguish different benign thyroid diseases and to diagnose benign and malignant thyroid diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Previous studies have indicated an association between vitamin D and thyroid- and parathyroid-related diseases. However, it remains unclear whether it is a cause of the disease, a side effect of treatment or a consequence of the disease. The Mendelian randomisation (MR) study strengthens the causal inference by controlling for non-heritable environmental confounders and reverse causation. In this study, a two-sample bidirectional MR analysis was conducted to investigate the causal relationship between serum vitamin D levels and thyroid- and parathyroid-related diseases. Inverse variance weighted, weighted median and MR-Egger methods were performed, the Cochran Q test was used to evaluate the heterogeneity and the MR-PRESSO and MR-Egger intercepts were utilised to assess the possibility of pleiotropy. The Bonferroni-corrected significance threshold was 0·0038. At the Bonferroni-corrected significance level, we found that vitamin D levels suggestively decreased the risk of benign parathyroid adenoma (OR = 0·244; 95 % CI 0·074, 0·802; P = 0·0202) in the MR analyses. In the reverse MR study, a genetically predicted risk of thyroid cancer suggestively increased the risk of elevated vitamin D (OR = 1·007; 95 % CI 1·010, 1·013; P = 0·0284), chronic thyroiditis significantly increased the risk of elevated vitamin D (OR = 1·007; 95 % CI 1·002, 1·011; P = 0·0030) and thyroid nodules was significantly decreased the vitamin D levels (OR = 0·991; 95 % CI 0·985, 0·997; P = 0·0034). The findings might be less susceptible to horizontal pleiotropy and heterogeneity ( P > 0·05). This study from a gene perspective indicated that chronic thyroiditis and thyroid nodules may impact vitamin D levels, but the underlying mechanisms require further investigation.

Thyroid nodules are a very common finding and have a malignancy rate of 7%-15%. Some malignant nodules have an indolent behavior and may not affect mortality if left untreated. Active surveillance (AS) is a strategy to prevent overtreatment in patients with papillary thyroid microcarcinomas (PTMCs). This review was conducted to evaluate the status of AS for low-risk PTMC in Latin America, including cultural and logistical challenges, disease progression data, and financial viability. We searched PubMed (MEDLINE), SciELO, LILACS, and Web of Science for articles published after 2014 and enrolling adult Latin American patients. Articles cited in the selected studies were also retrieved. We analyzed the AS protocols, technical or logistical challenges, patient adherence, reasons for AS interruption, surgical conversion rates, duration of AS, and disease progression during AS in our region. Three articles were included in the analysis, all of which considered AS a viable option and reported tumor progression and outcomes similar to those reported in other countries. Neck ultrasound and serum levels of thyroglobulin, thyroid-stimulating hormone (TSH), thyroxine (T4), and antithyroglobulin antibodies were included in the follow-up. No cases of new distant metastases were reported, and the outcomes were favorable when surgery was required. Anxiety was the main reason for AS interruption. We conclude that AS can be an acceptable approach and is safe and effective in Latin America, although more prospective studies are needed to consolidate this strategy in our region. Adequate infrastructure, follow-up, and patient education, as well as multidisciplinary healthcare teams trained in conducting AS must be ensured for successful results., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reporte

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: This study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC)., Methods: This prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis., Results: Serum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC., Conclusion: Serum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: The survival rate of patients with medullary thyroid carcinoma (MTC) who fail to achieve a biochemical cure after surgery is reduced. This study aimed to investigate the prognostic factors affecting the survival of MTC patients who do not achieve a biochemical cure after surgery., Methods: Cox univariate and multivariate proportional hazard models were used to determine the influence of different variables on overall survival (OS). Pearson's chi-square test was used for categorical variables, and paired t-test was used for continuous variables., Results: In our study of 277 MTC patients treated between 2012 and 2022, there were 96 with raised postoperative 1-month calcitonin (Ct) levels (0-9.52 pg/ml). The overall survival (OS) rates of patients with high postoperative 1-month Ct values at 1, 3, and 5 years were 97.9%, 94.6%, and 86.8%, respectively. The univariate analysis revealed that patients with a postoperative 1-month Ct > 441.9 pg/ml had a greater risk of mortality than patients with postoperative 1-month Ct values ranging from 9.52 to 73.4 pg/ml (p = 0.043). Subsequent analyses revealed that receiving targeted therapy did not improve the OS of patients with distant metastasis among those with high postoperative 1-month Ct values (p = 0.527)., Conclusion: This study confirmed that MTC patients who did not achieve biochemical remission after surgery had an increased risk of death when the Ct level was > 441.9 pg/ml 1 month after surgery. Additionally, for MTC patients who have not achieved biochemical remission and have experienced disease progression or distant metastasis after surgery, the use of targeted therapy does not prolong survival., (© 2024. The Author(s).)

Objective: This study aims to analyze the relationship between papillary thyroid carcinoma (PTC) and various factors., Methods: The study involved two groups-PTC patients and non-PTC controls. We utilized binary logistic regression and Least Absolute Shrinkage and Selection Operator (Lasso) regression for variable selection and risk factor analysis. Correlation analysis was performed using Spearman's rank correlation. The diagnostic value of thyroid stimulating hormone (TSH) levels for PTC was assessed using Receiver Operating Characteristic (ROC) curves., Results: PTC patients exhibited higher body mass index (BMI) (23.71 vs. 22.66, p<0.05) and TSH levels (3.38 vs. 1.59, p<0.05). Urinary iodine concentration (UIC) was an independent predictor of PTC (OR=1.005, p<0.05). The optimal TSH threshold for PTC diagnosis was 2.4 mIU/L [The Area Under the Curve (AUC)=67.3%, specificity=71.4%, sensitivity=70.1%]. TSH levels positively correlated with BMI (r=0.593, p<0.05) and UIC (r=0.737, p<0.05)., Conclusions: UIC may be an independent predictor of PTC, and TSH levels have some diagnostic value for identifying PTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Feng, Gao, Liu, Meng, Fan, Liu and Du.)

Thyroglobulin (Tg) is an important tool to evaluate the persistence and recurrence risk in differentiated thyroid cancer (DTC). We aimed to evaluate the correlation between pre-radioiodine therapy stimulated Tg (pre-RAI Tg) levels and the first response to treatment evaluation, and to establish a cut-off pre-RAI Tg threshold for predicting an initial excellent response. Retrospective cohort study of DTC patients who underwent total thyroidectomy and radioiodine therapy. Response to therapy was evaluated 6 to 24 months after initial therapy, and patients were classified as: excellent response (ER); indeterminate response (IndR) and incomplete response (IncR). Total patients: 166 among which 85.5% female with mean age of 47.6 ± 13 years. The ER had a significantly lower pre-RAI Tg in comparison to IndR (p<0.001) and IncR (p<0.001), and pre-RAI Tg were different between the IndR and IncR (p=0.02). A cut-off pre-RAI Tg value at 7.55ng/ml was obtained by receiver operating characteristics curve for differentiating ER from IndR and IncR. The area under curve was 0.832 (95% CI 0.76-0.91). In multivariate analysis, ATA low-risk (RR 1.61, 95% CI 1.06-2.43, p=0.025) and Tg below 7.55ng/ml (RR 2.17, 95% CI 1.52-3.10, p<0.001) were associated with ER. After a median of 7.4-year follow-up, 124 (74.7%) patients were allocated into ER, 22 (13.2%) into IndR, and 20 (12%) into IncR. In conclusion, pre-RAI Tg predicts first evaluation of treatment response. Pre-RAI Tg cut-off was a key predictor of initial excellent response to therapy and may be an important tool in the follow-up of DTC patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Although standard operational procedures for pre-therapeutic dosimetry already exist for the determination of the maximum safe activity to treat differentiated thyroid cancer patients, empiric activity administration of 131 I is still the most frequent way of treatment. In this way, the absorbed dose to the blood/bone marrow remains unknown., Purpose: In this work, we present a strategy to estimate radiation dose to the blood in an outpatient setting., Methods: A mobile application was developed, which together with an off-the-shelf compact semiconductor radiation detector allows the determination of whole-body time-integrated activity coefficients. The methodology was tested in a cohort of 79 differentiated cancer patients who received therapeutic 131 I activities. Post-therapeutic whole-body time-integrated activity coefficients were compared against pre-therapeutic estimates in a subset of 13 patients., Results: The 95% limits of agreement between pre whole-body and post whole-body time integrated activity coefficients were [-14.4; 6.6] h when considering outliers and [-6.2; 3.6] h without outliers. A high dispersion in blood dose coefficients was found, with a four-fold difference between the highest and lower values. Blood doses were significantly higher for patients treated with dosimetrically guided activities than for empirical activities (median dose = 118 vs. 49 cGy, respectively). Blood dose coefficients were significantly lower for patients prepared with recombinant human thyroid stimulating hormone (rhTSH) than for patients prepared with thyroid hormone withdrawal. A low correlation between blood dose and administered activity was found in empirically treated patients (R 2  = 0.26)., Conclusions: We successfully implemented a post-therapeutic internal dosimetry methodology for differentiated thyroid cancer therapy with 131 I, which allows to estimate dose to the blood from outpatient measurements with mobile devices. The proposed methodology avoids the need of daily visits to the nuclear medicine department, thus reducing the burden for the patient and for the staff., (© 2024 American Association of Physicists in Medicine.)

Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1-4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Early diagnosis of thyroid cancer is hampered by the inability of fine-needle aspiration biopsy (FNAB) to accurately classify ∼30% of cases while preoperative cancer staging detects lymph nodal involvement in only half of cases. Liquid biopsy may present an accurate, non-invasive alternative for preoperative thyroid nodule assessment. Thyrotropin receptor (TSHR) mRNA, a surrogate marker for circulating cancer cells (CTC), may be an option for early detection of malignancy from peripheral blood, but requires methodological improvements. We aimed to investigate if TSHR mRNA can be detected in low sample volumes by employing an ultrasensitive method - droplet digital PCR (ddPCR)., Methods: Less than 5 mL of blood was collected from 47 patients with thyroid nodules (25 benign and 22 malignant). RNA was isolated from the fraction of mononuclear cells where CTCs segregate. Samples were analysed for the presence of TSHR mRNA by ddPCR., Results: Thyrotropin receptor mRNA was detectable in 4 mL sample volumes, with the test having good specificity (80%) but modest diagnostic accuracy (68.1%). Combining TSHR mRNA with ultrasound features and FNAB diagnosis, the test reaches high rule-out performances (sensitivity = 90% and NPV = 88.2%). Strikingly, TSHR mRNA correctly classified all samples with thyroid capsule invasion, lymph node metastasis and extrathyroidal extension. If aggressiveness is defined using these parameters, TSHR mRNA test reaches 100% sensitivity and 100% NPV for detecting high-risk cases., Conclusions: Employing ddPCR for TSHR mRNA improves its measurement by enabling detection in sample volumes common for laboratory testing. The test displays high prognostic performance, showing potential in preoperative risk assessment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The prevalent histological variant within differentiated thyroid carcinoma is papillary thyroid carcinoma, also known as PTC. The study investigated the clinical performance of serum hsa&#95;circ&#95;0001955 in predicting the prognosis of PTC treated with radical thyroidectomy and iodine 131 nail clearance. The relative expression of serum circ&#95;0001955 of PTC patients was detected before and after accepting radical thyroidectomy combined with 131I thyroid remnant ablation by RT-qPCR. Serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels were quantified by an automatic chemiluminescence immunoassay analyzer. Multivariate logistic regression analysis was employed to investigate the risk factors associated with the prognosis of PTC patients with postoperative 131I therapy. The serum circ&#95;0001955 levels in 127 PTC patients were higher than that in 96 multinodular goiter patients and 110 healthy controls before treatment and had diagnostic values for PTC patients. After 131I treatment, serum circ&#95;0001955 levels and Tg value have a correlation with potential recurrence (WBS positive). Serum circ&#95;0001955, Tg, and TgAb value, and their combination may have diagnostic value in predicting recurrence. Serum circ&#95;0001955 levels in patients with PTC after radical thyroidectomy and iodine 131 thyroidectomy may help predict recurrence.

Medullary thyroid carcinoma (MTC) comprises less than 5% of thyroid cancers but is responsible for over 10% of deaths related to thyroid cancer. Regional lymph node metastasis is common and associated with mortality, thus total thyroidectomy with central compartment lymph node dissection is the standard surgical treatment for MTC. In this best practice submission, we aim to review the existing literature and determine whether calcitonin levels can serve as a reliable method for risk-stratifying MTC without overt lymph node involvement., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Calcitonin is a sensitive marker for medullary thyroid carcinoma (MTC) diagnosis and postsurgical follow-up. This study aimed to define the gender and tumor size-specific calcitonin cutoff values for diagnosing MTC., Methods: This retrospective study recruited 95 MTC patients and 10,523 non-MTC patients who underwent thyroid nodule surgery at Zhongshan Hospital between January 2015 and June 2023. Receiver operating characteristic (ROC) curves were used to assess calcitonin cutoff values for diagnosing MTC., Results: Calcitonin levels in non-MTC patients were influenced by gender, CKD stage and age, with gender being the highest ranked predictor. In MTC patients, calcitonin levels were associated with tumor diameter, lymph node metastasis, and TNM stage. In the entire study population, calcitonin cutoff values to diagnose MTC were 17.75 pg/mL for males (sensitivity: 97.60%, specificity: 99.40%) and 7.15 pg/mL for females (sensitivity: 94.34%, specificity: 99.22%). In patients with a thyroid nodule diameter ≤10 mm, the calcitonin cutoff values to diagnose MTC were 17.50 pg/mL for males (sensitivity: 95.00%, specificity: 99.27%) and 7.15 pg/mL for females (sensitivity: 90.91%, specificity: 99.04%). In patients with a thyroid nodule diameter >10 mm, the calcitonin cutoff values to diagnose MTC were 104.80 pg/mL for males (sensitivity: 100.00%, specificity: 100.00%) and 32.60 pg/mL for females (sensitivity: 96.77%, specificity: 100.00%)., Conclusion: We have identified the gender and tumor size-specific cutoff values for the diagnosis of MTC. Cutoff values based on gender and tumor diameter may help to improve the accuracy of preoperative diagnosis of MTC, which is worth to be verified by future studies., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Zhongshan Hospital affiliated to Fudan University. Consent to participate Written informed consent was obtained from the parents., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown., Patients and Methods: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC., Results: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes., Conclusion: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis., (© 2024. The Author(s).)

Introduction: The thyroid cancer has the ninth larger incidence of cancer in the world. Investigations related to the exposure to metals have become important due to the sensibility of the thyroid gland to them. Studies reveal that carcinogenic progressions are associated to the deficiency of the essential trace elements. In this context, the zinc is highlighted, essential for the metabolism of the thyroidal hormone and has a potential relation with the pathogenesis of the thyroid cancer. The objective of this systematic review and meta-analysis is to evaluate the low serum zinc as a risk factor for thyroid cancer in adults., Methods and Analysis: PubMed/MEDLINE, Scopus, Embase and LILACS databases will be searched for observational studies investigating the low serum zinc as a risk factor for thyroid cancer in adults. No language or publication period restrictions will be imposed. The primary outcome will be that the low serum zinc is a risk factor for thyroid cancer. Three independent reviewers will select the studies and extract data from the original publications. The risk-of-bias will be assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data synthesis will be performed using the R software (V.4.3.1) and to assess heterogeneity, we will compute the I2 statistic and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence., Prospero Registration Number: International Prospective Register of Systematic Reviews (PROSPERO) CRD42023463747., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Soares et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To analyze the relationship between serum microRNA-221 and microRNA-451 expression and the pathological features and prognosis of patients with thyroid papillary carcinoma., Methods: Cross-sectional study that included 120 patients with papillary thyroid cancer treated at the hospital and 120 healthy volunteers selected as the control group who underwent physical examination. The relative expression levels of microRNA-221 and microRNA-451 were compared between the thyroid papillary carcinoma group (prior to treatment) and the control group. Additionally, microRNA-221 and microRNA-451 expression levels were analyzed in patients with papillary thyroid carcinoma across different pathological characteristics., Results: Serum microRNA-221 relative levels were significantly higher (p<0.001) in the papillary carcinoma group compared to the control group, while microRNA-451 levels were higher in the control group (p<0.001). In the papillary carcinoma group, microRNA-221 expression was significantly higher in patients with extracapsular invasion (p<0.001), lymphatic metastasis (p=0.003), and poor prognosis (p<0.001). Conversely, microRNA-451 expression was significantly lower (p<0.001) in patients with extracapsular invasion, lymphatic metastasis and poor prognosis. In the multivariate logistic regression analysis, morphological features suggestive of an aggressive clinical behavior (extracapsular invasion and lymphatic metastasis) were related to high expression of microRNA-221 and low expression of microRNA-451 in patients with thyroid papillary carcinoma (p<0.001)., Conclusions: Serum microRNA-221 and microRNA-451 expression levels are significantly higher and lower, respectively, in patients with papillary thyroid carcinoma, particularly in patients with morphological features suggestive of an aggressive clinical behavior (extracapsular invasion and lymphatic metastasis) and, therefore, of a poor prognosis.

As the most common endocrine cancer, thyroid cancer (TC) has sharply increased globally over the past three decades. The growing incidence of TC might be counted by genetics, radiation, iodine, autoimmune disease, and exposure to environmental endocrine-disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs), being typical EDCs, have been widely utilized in plastics, electronics, furniture, and textiles as flame retardants since the 1980s, and research has indicated a significant correlation between their exposure and the risk of TC. Even so, PBDEs exposure impact on the metabolic signature for TC remains unexplored. In this study, eight congeners of PBDEs were determined in serum from 111 patents with papillary thyroid cancer (PTC) and 111 healthy participants based on case-control epidemiology using gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (GC-APCI-MS/MS). Based on the tertile distribution of total PBDEs concentrations in 59 participants, metabolomics analysis was further performed by ultra-high performance liquid chromatography coupled to hybrid quadrupole-Orbitrap MS. In the partial correlation analysis, the 29 identified metabolites were correlated with PBDEs exposure (P < 0.05). In addition, PBDEs disrupted the metabolism of glycerophospholipids, sphingolipids, taurine, and hypotaurine, indicating that neurotransmitters, oxidative stress, and inflammation are the vulnerable pathways affected in PTC. Furthermore, (±)-octopamine and 5-hydroxyindole, both of which modulate the actions of neurotransmitters, emerged as potential disturbed metabolite markers for TC following exposure to PBDEs. This study analyzed the impact of PBDEs on PTC in terms of the metabolic changes and further explored possible biomarkers, which helped us have a deep understanding of the possible mechanism of the effects of PBDEs on TC., (© 2024. The Author(s).)

Objective: Levothyroxine (LT 4 ) monotherapy is the current recommended approach for treating pediatric patients post-total thyroidectomy (TT) based on the assumption that peripheral conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ) normalizes thyroid hormone levels. In adults, approximately 15% of post-TT patients on LT4 monotherapy have altered T 4 :T 3 ratios with ongoing debate in regard to the clinical impact with respect to health-related quality of life (hrQOL). The ability to normalize T 3 and T 4 levels on LT 4 monotherapy for pediatric patients' post-TT is important but not previously described. This study reports data on T 3 levels in athyreotic pediatric patients to determine if a similar cohort of patients exists on LT4 monotherapy targeting normalization of TSH (LT4 replacement) or suppression (LT4 suppression)., Methods: Thyroid function tests (TFTs) were retrospectively extracted from medical charts for patients <19 years old who underwent TT for definitive treatment of Graves' disease (GD) or differentiated thyroid cancer (DTC) between 2010-2021. LT4 dosing was selected to normalize the TSH in GD patients (LT4 replacement) or suppress TSH in DTC patients (LT4 suppression). Pre- and post-surgical TSH, T3 and T4 levels were compared., Results: Of 108 patients on LT 4 replacement (n=53) or LT 4 suppression (n=55) therapy, 94% (102/108) of patients demonstrated T 3 levels in the normal range post-TT. However, the majority of patients on LT 4 replacement (44/53; 83%) and LT 4 suppression (31/55; 56%) displayed post-TT T 3 levels in the lower half of the normal range despite 50% (22/44) and 48% (15/31) of these patients, respectively, having post-TT fT 4 levels above the upper limit of the normal range., Conclusion: A significant number of pediatric patients do not achieve similar T 3 and T 4 :T 3 levels pre- and post-TT. Future multi-center, prospective studies evaluating LT 4 monotherapy in comparison to combined LT 4 /LT 3 therapy are warranted to determine the potential clinical impact of altered T3 levels in athyreotic pediatric patients., Competing Interests: AB is a consultant for IBSA Pharm and Rare Thyroid Therapeutics/Egetis Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baran, Isaza, Bojarsky, Alzoebie, Song, Halada, Sisko, Gonzales, Mostoufi-Moab and Bauer.)

Context: Telomerase reverse transcriptase (TERT) promoter-mutated thyroid cancers are associated with a decreased rate of disease-free and disease-specific survival. High-quality analytical validation of a diagnostic test promotes confidence in the results that inform clinical decision-making., Objective: This work aimed to demonstrate the analytical validation of the Afirma TERT promoter mutation assay., Methods: TERT promoter C228T and C250T variant detection in genomic DNA (gDNA) was analyzed by assessing variable DNA input and the limit of detection (LOD) of variant allele frequency (VAF). The negative and positive percentage agreement (NPA and PPA) of the Afirma TERT test was examined against a reference primer pair as was the analytical specificity from potential interfering substances (RNA and blood gDNA). Further, the intrarun, interrun, and interlaboratory reproducibility of the assay were tested., Results: The Afirma TERT test is tolerant to variation in DNA input amount (7-13 ng) and can detect expected positive TERT promoter variants down to 5% VAF LOD at 7 ng DNA input with greater than 95% sensitivity. Both NPA and PPA were 100% against the reference primer pair. The test remains accurate in the presence of 20% RNA or 80% blood gDNA for an average patient sample that typically has 30% VAF. The test also demonstrated a 100% confirmation rate when compared with an external next-generation sequencing-based reference assay executed in a non-Veracyte laboratory., Conclusion: The analytical robustness and reproducibility of the Afirma TERT test support its routine clinical use among thyroid nodules with indeterminate cytology that are Afirma Genomic Sequencing Classifier suspicious or among Bethesda V/VI nodules., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive thyroid cancers with poor prognosis. At present, there are a limited number of research reports on PDTC and ATC. The study aimed to analysis the predictive value of hematologic parameters and clinicopathological features of PDTC and ATC., Methods: This study retrospectively analyzed 67 patients at Tianjin Medical University Cancer Hospital from 2007 to 2019. We analyzed the clinicopathological features and survival outcomes of PDTC and ATC., Results: This study showed that positive D-dimer, a high NLR, and a high PLR were more common in death patients. At the end of follow-up, 22 (32.8%) patients were alive at the time of study and 45 (67.2%) patients died from thyroid carcinoma. Disease-related death rates were 93.8% in ATC and 42.9% in the PDTC group. The median overall survival (OS) was 2.5 (0.3-84) months for patients with ATC, and 56 (3-113) months of PDTC patients. Univariate analysis showed that age at diagnosis and surgery were associations with OS in ATC patients, what's more, age at diagnosis, a high NLR, a high PLR, and positive D-dimer were associations with OS in PDTC patients. Multivariate analysis revealed that age at diagnosis was an independent association with OS in ATC patients., Conclusions: The hematologic parameters and clinicopathological features may provide predictive value of prognosis for patients with PTDC and ATC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To explore the impact of lymph node diameter on the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of cervical metastatic lymph nodes (CMLNs) from thyroid cancer., Methods: A total of 32 patients with 58 CMLNs from thyroid cancer underwent ultrasound-guided MWA and were included in the retrospective study. Patients were divided into three groups based on the mean largest diameter of the CMLNs: Group A (diameter ≤10mm), Group B (10mm < diameter ≤20mm), and Group C (diameter >20mm). The research involved comparing changes in cervical metastatic lymph nodes and serum thyroglobulin (sTg) levels, as well as the incidence of complications, before and after microwave ablation across three groups of patients., Results: The technical success rate of this study was 100% (32/32), and they showed no major complications. Compared with measurements taken before MWA, the mean largest diameter and volume of CMLNs, as well as the sTg level, showed significant reductions ( p < 0.05) at the last follow-up in all three patient groups. Group A and B exhibited higher lymph node volume reduction rates and complete disappearance rates compared to Group C. However, the recurrence rate in the three groups were in the following order: Group C > Group B > Group A. The occurrence rate of mild complications was Group A > Group C > Group B., Conclusion: MWA is a safe and effective method for treating CMLNs, with advantages for localized nodes but limitations for larger ones. Careful consideration and personalized plans are advised, based on comprehensive evidence assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Chen, Li, Li and Zhu.)

Purpose: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery., Methods: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS)., Results: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307)., Conclusion: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6β-hydroxycortisol, deoxycholic acid, and 1β-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: Progastrin-releasing peptide (ProGRP) is the precursor of the gastrin-releasing peptide, a neuropeptide secreted by cells of neural and endocrine origin. Recently, ProGRP has emerged as a circulating biomarker for small cell lung cancer (SCLC), a subtype of aggressive and poorly differentiated neuroendocrine neoplasm (NEN). Given the ability of the neuroendocrine SCLC cells to secrete this peptide, we performed an in-depth narrative review aimed at collecting, summarizing, and critically analyzing the available literature about the possible value of ProGRP as a biomarker for pulmonary NENs other than SCLC, and for NENs of non-pulmonary origin., Methods: We conducted an extensive search on international databases (PubMed, Web of Science, and Scopus)., Results: We selected 21 pertinent published articles (12 original studies and 9 case reports). Overall, the original studies included 1,711 patients, and the case reports described the clinical course of 10 patients., Conclusion: The data analyzed suggest a potential role for ProGRP as a diagnostic biomarker for typical and atypical lung carcinoids, pulmonary large cell neuroendocrine carcinoma, medullary thyroid carcinoma, non-pulmonary neuroendocrine carcinomas, prostate cancer with neuroendocrine differentiation, and the pancreatobiliary neuroendocrine carcinoma. Despite these promising results, additional studies are needed, to clarify the role of ProGRP as the diagnostic biomarker for specific NENs.

Background: Intraoperative neural monitoring (IONM) has been utilized for a variety of thyroid pathologies, including papillary thyroid carcinoma (PTC). Remnant thyroid tissue following total thyroidectomy (TT) in patients with PTC is associated with increased recurrence. The aim of this study is to investigate whether the use of IONM in PTC surgery has an impact on the completeness of thyroidectomy., Methods: Retrospectively, patients with preoperative diagnosis of PTC, who underwent TT in a tertiary center were reviewed. They were grouped based on the IONM usage, and 1:1 propensity-score match was performed. Primary outcome was the completeness of thyroidectomy, determined by measuring postoperative stimulated thyroglobulin levels (sTg)., Results: Among 274 clinically node-negative PTC patients who underwent TT and ipsilateral prophylactic central lymph-node dissection, a total of 170 patients (85:85) were matched. Postoperative sTg levels were significantly lower in the IONM group (1 ng/dL vs. 0.4 ng/dL; p  < 0.01) with higher percentage of the patients with sTg levels <1 ng/ml (50.6% vs. 69.4%; p  = 0.01). More patients in the no-IONM group received RAI ablation with significantly higher doses (mean mci: 120 vs. 102; p  = 0.02)., Conclusion: The use of IONM during thyroidectomy provides improvement in the completeness of thyroidectomy and reduction in postoperative sTg levels which can be used as a guide by clinicians to avoid RAI ablation in selected PTC patients and to adjust low ablative doses in patients who are scheduled for remnant ablation.

Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to investigate the expression of microRNAs (miRNAs) -146b-3p, -221-5p, -222-3p, and -21a-3p and the methylation pattern of the thyroid-stimulating hormone receptor ( TSHR ) gene in blood plasma samples from papillary thyroid cancer (PTC) patients before and after thyroidectomy compared to healthy controls (HCs). This study included 103 participants, 46 PTC patients and 57 HCs, matched for gender and age. Significantly higher preoperative expression levels of miRNAs and TSHR methylation were determined in the PTC patients compared to HCs. Post-surgery, there was a notable decrease in these biomarkers. Elevated TSHR methylation was linked to larger tumor sizes and lymphovascular invasion, while increased miRNA-222-3p levels correlated with multifocality. Receiver operating characteristic (ROC) analysis showed AUCs below 0.8 for all candidate biomarkers. However, significant changes in the expression of all analyzed miRNAs and TSHR methylation levels indicate their potential to differentiate PTC patients from healthy individuals. These findings suggest that miRNAs and TSHR methylation levels may serve as candidate biomarkers for early diagnosis and monitoring of PTC, with the potential to distinguish PTC patients from healthy individuals. Further research is needed to validate these biomarkers for clinical application.

Purpose: Collecting venous blood samples from patients post administration of high therapeutic activities results in radiation exposure to staff collecting the blood. This study investigated the use of finger-tip capillary-blood collection as an alternative to the venous-blood collection method recommended by the European Association of Nuclear Medicine (EANM) dosimetry protocol for quantifying 131 I concentration in the critical organ after therapeutic dose of 131 I., Methods: The study included differentiated thyroid cancer patients referred to a thyroid cancer centre at St James's Hospital, Ireland, for therapeutic and diagnostic oral administration of 131 I. The 15 patients recruited for this study provided 30 venous and capillary paired-blood samples. The activity concentration of the blood samples was compared between the type of blood (venous vs capillary) and the geometry/volume of the blood (1.0 ml versus 0.03 ml). Other variables were also investigated including administered activities, dose to staff performing the sampling, duration of sampling and time since administration., Results: Blood samples were taken at 2.0-91.9 h post administration using 0.2 ± 0.0 GBq (n = 2) or 4.0 ± 0.1 GBq (n = 28) 131 I activities. There was no significant difference found between different blood sampling types (-1.0 ± 4.3 %, p = 0.223), different blood volumes (-3.2 ± 10.0 %, p = 0.070), or between their combination. No significant correlation was found between the percentage differences and investigated parameters., Conclusion: A high degree of accuracy was achieved with blood radioactivity quantified using capillary blood collection using the finger-prick method. Further validation of the method would be required prior to implementation, to investigate patient specific factors which may affect accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Conflicts of interest and sources of funding: none declared. This work was supported by the National Cancer Center Grants (NCC-2112570-1) from the National Cancer Center (Republic of Korea)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This paper reports the diagnostic process of a case involving an 86-year-old male patient who was admitted with cough, sputum, and fever, accompanied by persistent leukocytosis., Methods: Through a multidisciplinary team (MDT) discussion, the laboratory department identified elevated ferritin levels, prompting clinical consideration of potential malignancy., Results: Further investigations confirmed the diagnosis of thyroid cancer with multiple lung metastases., Conclusions: This case highlights the potential value of ferritin in tumor diagnosis, offering new insights into the etiology of abnormal leukocyte elevation. Additionally, the active involvement of the laboratory department in MDT discussions proves to be crucial for diagnosing challenging cases.

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Iodine deficiency-induced goiter continues to be a global public health concern, with varying manifestations based on geography, patient's age, and sex. To gain insights into clinical occurrences, a retrospective study analyzed medical records from patients with iodine deficiency-induced goiter or thyroid cancer who underwent surgery at the Community Hospital in Riehen, Switzerland, between 1929 and 1989. Despite today's adequate iodine supplementation, a significant risk for iodine-independent goiter remains in Switzerland, suggesting that genetic factors, among others, might be involved. Thus, a pilot study exploring the feasibility of genetic analysis of blood spots from these medical records was conducted to investigate and enhance the understanding of goiter development, potentially identify genetic variations, and explore the influence of dietary habits and other environmental stimuli on the disease.Blood prints from goiter patients' enlarged organs were collected per decade from medical records. These prints had been made by pressing, drawing, or tracing (i.e., pressed and drawn) the removed organs onto paper sheets. DNA analysis revealed that its yields varied more between the prints than between years. A considerable proportion of the samples exhibited substantial DNA degradation unrelated to sample collection time and DNA mixtures of different contributors. Thus, each goiter imprint must be individually evaluated and cannot be used to predict the success rate of genetic analysis in general. Collecting a large sample or the entire blood ablation for genetic analysis is recommended to mitigate potential insufficient DNA quantities. Researchers should also consider degradation and external biological compounds' impact on the genetic analysis of interest, with the dominant contributor anticipated to originate from the patient's blood., (© 2024. The Author(s).)

Purpose: Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules., Methods: Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017)., Results: Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older., Conclusion: Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy., (© 2024. The Author(s).)