Benign Thyroid Nodules Research Articles

Long-term clinical outcomes of thermal ablation for benign thyroid nodules and unresolved issues: a comprehensive systematic review

Long-term clinical outcomes of thermal ablation for benign thyroid nodules and unresolved issues: a comprehensive systematic review

Radiomics analysis of dual-energy CT-derived iodine maps for differentiating malignant from benign thyroid nodules.

Many thyroid nodules are detected incidentally with the widespread use of sensitive imaging techniques; however, only a fraction of these nodules are malignant, resulting in unnecessary medical expenditures and anxiety. The major challenge is to differentiate benign thyroid nodules from malignant ones. The application of dual-energy computed tomography (DECT) and radiomics provides a new diagnostic approach. Studies applying radiomics from primary tumours on iodine maps to differentiate malignant from benign thyroid nodules are still lacking. To determine the ability of an iodine map-based radiomic nomogram in the venous phase for differentiating malignant thyroid nodules from benign nodules. A total of 141 patients with thyroid nodules who underwent DECT were enrolled and randomly assigned to the training and test cohorts between January 2018 and January 2019. The radiomic score (Rad-score) was derived from nine quantitative features of the iodine maps. Stepwise logistic regression analysis was used to develop radiomic, clinical and combined models. Age, normalized iodine concentration (NIC), and cyst changes were used to construct the clinical model. Receiver operating characteristic (ROC) curve analysis, sensitivity and specificity were performed to analyse the ability of the models to predict malignant thyroid nodules. Calibration analysis was used to test the fitness of the models. Decision curve analysis (DCA) and nomogram construction were also performed. According to the clinical model, age (0.989 [0.984, 0.995]; p<0.001), NIC (0.778 [0.640, 0.995]; p=0.01), and cyst changes (0.617 [0.507, 0.751]; p<0.001) were independently associated with malignant thyroid nodules. According to the combined model, age (0.994 [0.989, 0.999]; p=0.01), NIC (0.797 [0.674, 0.941]; p=0.008), cyst changes (0.786 [0.653, 0.947]; p=0.01), and the rad-score (1.106 [1.070, 1.143]; p<0.001) were independently associated with malignant thyroid nodules. The combined model achieved satisfactory discrimination in predicting malignant thyroid nodules and had greater predictive value in the training (AUC [areas under the curve], 0.96vs. 0.87; p=0.01) and test (AUC, 0.90vs. 0.79; p=0.04) cohorts than did the clinical model. The radiomics nomogram based on iodine maps is useful to distinguish malignant thyroid nodules from benign thyroid nodules.

The value of NGS-based multi-gene testing for differentiation of benign from malignant and risk stratification of thyroid nodules

BackgroundFine-needle aspiration (FNA) biopsy is typically used in conjunction with cytopathologic evaluation to differentiate between benign and malignant thyroid nodules. Even so, the cytology results for 20-30% of thyroid nodules are indeterminate. This study sought to evaluate the usefulness of next-generation sequencing (NGS)-based multi-gene panel testing for risk stratification and the differentiation of benign from malignant thyroid nodules.MethodsThyroid nodule samples were obtained from a cohort of 359 patients who underwent FNA. An NGS-based multi-gene panel testing was conducted for these samples, in which single-nucleotide variants (SNVs) and small insertion/deletions (InDels) can be detected in 11 genes and fusion events can be identified in 5 genes. Surgical resection was conducted for 113 patients (113/359), and then histopathology results were obtained.ResultsIn comparison to cytology alone, the diagnostic sensitivity of NGS combination cytology increased from 0.7245 (95% CI: 0.6289-0.8032) to 0.898 (95% CI: 0.8223-0.9437); the associated AUC was 0.8303 (vs. Cytology AUC: 0.7622, P &amp;lt; 0.001). BRAFV600E was identified in 136 patients, of whom 79 underwent surgery and were diagnosed with papillary thyroid carcinoma (PTC) pathologically. TERT promoter mutations or BRAF/RAS co-mutations with other genes were identified in 5 patients, while 4 patients were diagnosed with malignant thyroid cancer using the pathological method. RAS mutations were identified in 27 patients, while 10 patients underwent surgery, which showed that 3 patients were classified as PTC and 7 cases were benign. In addition, 4 RET fusions, 1 RET activation mutation, and 3 TP53 inactivation mutations were identified in the remaining 8 patients who have not undergone surgery. Negative genetic test results or variants with uncertain significance were identified in 183 patients. Among these patients, 12 malignant thyroid tumors, including 11 PTC and 1 MTC, were diagnosed in 20 patients who received surgery.ConclusionThyroid nodules coupled with BRAFV600E, TERT promoter variants, BRAF/RAS co-mutations with other genes, RET fusions, and RET activating mutations were classified as high-risk. Nodules with RAS mutations (NRAS, KRAS, HRAS) and TP53 inactivating mutations were considered to be in the intermediate-risk group, while those with non-pathogenic mutations (negative and variants of uncertain significance) were placed in the low-risk group. When combined with cytopathology, NGS increases the sensitivity of diagnosing benign and malignant thyroid nodules, and the reference is useful for patient risk stratification.

Artificial intelligence-enhanced infrared thermography as a diagnostic tool for thyroid malignancy detection

Introduction Thyroid nodules are common, and investigation is crucial for excluding malignancy. Increased intranodular vascularity is frequently observed in malignant tumors, which can be detected through increased skin surface temperatures using noninvasive infrared thermography. We aimed to develop a diagnostic tool for thyroid cancer using infrared thermal images combined with an artificial intelligence (AI) algorithm. Methods We conducted a prospective cross-sectional study involving participants with thyroid nodules undergoing thyroid surgery. Infrared thermal images were collected using a thermal camera on the day prior to surgery. In combination with the final thyroid pathological reports, we utilized a machine learning model based on the pre-trained ResNet50V2 model, a convolutional neural network, to evaluate diagnostic accuracy for malignancy diagnosis. Results The study included 98 participants, 58 with malignant thyroid nodules and 40 with benign thyroid nodules, as determined by pathological results. The AI-enhanced infrared thermal image analyses demonstrated good performance in distinguishing between benign and malignant thyroid nodules, achieving an accuracy of 75% and a sensitivity of 78%. These parameters were slightly lower than those of the AI-model predictor that integrated current practice using preoperative thyroid ultrasound findings and cytological results, yielding an accuracy of 81% and a sensitivity of 84%. Conclusions The infrared thermal images, assisted by an AI model, exhibit good performance in distinguishing thyroid malignancy from benign nodules. This imaging modality has great potential to be used as a noninvasive screening tool for adjunct evaluation of thyroid nodules.

Contrast-Enhanced Ultrasound for Diagnosing Thyroid Nodules With Indeterminate Cytology: A Retrospective Study.

A small number of thyroid nodules cannot be clearly diagnosed using ultrasound-guided fine needle aspiration biopsy. Contrast-enhanced ultrasound (CEUS) has high diagnostic performance for thyroid nodules. We explored the value of CEUS for diagnosing thyroid nodules with indeterminate cytology. Between September 2019 and July 2022, 27,646 patients with thyroid nodule(s) underwent conventional ultrasound (CUS) in our hospital. From these patients, 597 nodules were subjected to CEUS and ultrasound-guided fine needle aspiration biopsy and 116 thyroid nodules with indeterminate cytology diagnose were enrolled in this study. The independent risk factors for predicting malignancy were determined using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were drawn for CUS, CEUS, and CEUS combined with CUS. The area under the curve (AUC) was calculated and compared. Of the 116 thyroid nodules, 40 (34.5%) were benign and 76 (65.5%) were malignant. Univariate analysis showed that the shape, echogenicity, margin, microcalcification, enhancement intensity, enhancement homogeneity, wash in, and wash out were significantly different between benign and malignant thyroid nodules (all p < 0.05). Multivariate logistic regression analysis showed that taller-than-wide, irregular margin, microcalcification, hypo-enhancement, heterogeneity enhancement, synchronous/slower wash in, and synchronous/slower wash out were independent risk factors for malignancy (all p < 0.05). ROC curve analysis showed that the AUC of CUS and CEUS were 0.769 and 0.848, respectively. No significant difference was observed in the AUC between the two modalities (p > 0.05). However, the AUC (0.934) of the CUS combined with CEUS was significantly higher than that of CEUS or CUS alone (both p < 0.05). CEUS is helpful in diagnosing thyroid nodules with indeterminate cytology. CUS combined with CEUS is highly valuable for predicting malignancy.

The genomic landscape of papillary thyroid carcinoma on next-generation sequencing in patients undergoing total thyroidectomy.

Thyroidectomy is increasingly performed for suspected malignancy. This cohort study aimed to identify genetic markers associated with malignancy and determine the molecular landscape of papillary thyroid carcinoma (PTC) through next-generation sequencing (NGS) in patients undergoing total thyroidectomy. Among 116 surgical candidates, 103 patients (age=42.9±13.7years; Male: Female=14:89) with benign or malignant thyroid nodules were eligible. Live thyroid tissue samples harvested intraoperatively with adequate DNA and RNA yield were subjected to NGS on the Illumina NovaSeq 6000 platform for genomic and transcriptomic analysis, respectively. Histopathology comprised 20 malignant (19.4%) and 83 benign (80.6%) cases, including 16 PTC (15.5%) cases. On NGS, single nucleotidepolymorphisms (SNPs) in NTRK1 at NC_000001.11:156879016 on chromosome 1 and ALK at NC_000002.12:29717663 on chromosome 2 were frequent in malignant lesions (p<0.05). A SNP in ALK at NC_000002.12:29193706 was consistently a homozygous alternate alleleacross the cohort. DNA-sequencing of PTC lesions identified recurrentsomatic mutations in BRAF (100%), ALK (56.3%), RET (18.8%), PIK3CA (12.5%), NTRK1 (12.5%), NTRK2 (87.5%), NTRK3(12.5%), NRAS(6.3%), and PTCH1 (31.3%) genes. RNA sequencing revealednovelfusiongenes, including MKRN1-BRAF, RN7SL1-CDH1, IRF2BPL-MED12, MED12-IRF2BPL, CPM-MDM2, and AC005895.3-PDGFRB. Inreceiveroperative characteristics analysis, the AUCs ofALKmutationpredictingrecurrence and metastases were 0.818 and 0.783. This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases. CTRI/2020/09/027607dt 04/09/2020; REF/2020/08/036119.

Do as Sonographers Think: Contrast-Enhanced Ultrasound for Thyroid Nodules Diagnosis via Microvascular Infiltrative Awareness.

Dynamic contrast-enhanced ultrasound (CEUS) imaging can reflect the microvascular distribution and blood flow perfusion, thereby holding clinical significance in distinguishing between malignant and benign thyroid nodules. Notably, CEUS offers a meticulous visualization of the microvascular distribution surrounding the nodule, leading to an apparent increase in tumor size compared to gray-scale ultrasound (US). In the dual-image obtained, the lesion size enlarged from gray-scale US to CEUS, as the microvascular appeared to be continuously infiltrating the surrounding tissue. Although the infiltrative dilatation of microvasculature remains ambiguous, sonographers believe it may promote the diagnosis of thyroid nodules. We propose a deep learning model designed to emulate the diagnostic reasoning process employed by sonographers. This model integrates the observation of microvascular infiltration on dynamic CEUS, leveraging the additional insights provided by gray-scale US for enhanced diagnostic support. Specifically, temporal projection attention is implemented on time dimension of dynamic CEUS to represent the microvascular perfusion. Additionally, we employ a group of confidence maps with flexible Sigmoid Alpha Functions to aware and describe the infiltrative dilatation process. Moreover, a self-adaptive integration mechanism is introduced to dynamically integrate the assisted gray-scale US and the confidence maps of CEUS for individual patients, ensuring a trustworthy diagnosis of thyroid nodules. In this retrospective study, we collected a thyroid nodule dataset of 282 CEUS videos. The method achieves a superior diagnostic accuracy and sensitivity of 89.52% and 94.75%, respectively. These results suggest that imitating the diagnostic thinking of sonographers, encompassing dynamic microvascular perfusion and infiltrative expansion, proves beneficial for CEUS-based thyroid nodule diagnosis.

In Search of Relevant Urinary Biomarkers for Thyroid Papillary Carcinoma and Benign Thyroid Nodule Differentiation, Targeting Metabolic Profiles and Pathways via UHPLC-QTOF-ESI+-MS Analysis.

Identification of specific urine metabolic profiles for patients diagnosed with papillary thyroid carcinoma (TC) vs. benign nodules (B) to identify specific biomarkers and altered pathways compared to those of healthy controls (C). Patient urine samples were collected, before surgery and after a histological confirmation of TC (n = 30) and B (n = 30), in parallel with sample collection from healthy controls (n = 20). The untargeted and semi-targeted metabolomic protocols were applied using UPLC-QTOF-ESI+-MS analysis, and the statistical analysis was performed using the Metaboanalyst 6.0 platform. The results for the blood biomarkers, previously published, were compared with the data obtained from urine sampling using the Venny algorithm and multivariate statistics. Partial least squares discrimination, including VIP values, random forest graphs, and heatmaps (p < 0.05), together with biomarker analysis (AUROC ranking) and pathway analysis, suggested a specific model for the urinary metabolic profile and pathway alterations in TC and B vs. C, based on 190 identified metabolites in urine that were compared with the serum metabolites. By semi-targeted metabolomics, 10 classes of metabolites, considered putative biomarkers, were found to be responsible for specific alterations in the metabolic pathways, from polar molecules to lipids. Specific biomarkers for discrimination were identified in each class of metabolites that were either upregulated or downregulated when compared to those of the controls. The lipidomic window was the most relevant for identifying biomarkers related to thyroid cancer and benign conditions, since this study detected a stronger involvement of lipids and selenium-related molecules for metabolic discrimination.

Somatic DICER1-Mutant Benign Thyroid Nodules in Adults: A Group of Follicular Nodular Disease With Continuous Growth.

Germline DICER1 mutations cause familial multinodular goiter (MNG). However, the prevalence of somatic DICER1 mutations in non-MNG benign thyroid nodules and their characteristics remain unknown. Adult-onset thyroid nodules with a pathological diagnosis were genotyped via targeted sequencing. DICER1-mutant nodules were assessed clinically and pathologically. Organoids were established to investigate follicular formation and growth. Transcriptomic analysis was conducted to evaluate transcriptional features, which were validated by immunofluorescence. Among 931 adult-onset thyroid nodules, we identified 13 benign thyroid nodules with DICER1 hotspot mutations. The majority harbored a somatic DICER1 hotspot mutation with a somatic DICER1 truncating variant. Clinically, 38.5% of the DICER1-mutant nodules exhibited substantial growth. DICER1-mutant nodules with durations longer than 2 years were substantially enlarged (P=.0448). Pathologically, all DICER1-mutant nodules were defined as thyroid follicular nodular disease (TFND). The TFND nodules with DICER1 mutations grew faster than those with wild-type DICER1. Organoid culture of a DICER1-mutant nodule revealed increased active follicular formation. Compared with the normal thyroid tissues, the DICER1-mutant nodules had comparable thyroid differentiation scores, significantly higher ERK scores (P=.0141) and lower epithelial‒mesenchymal transition scores (P=.0001). Moreover, the expression of genes related to follicular polarity, such as CDH16, SLC5A5, TSHR and TPO, was downregulated in the DICER1-mutant nodules. Somatic DICER1 two-hit mutations represent a notable percentage in adult TFND patients, and DICER1-mutant benign thyroid nodules were characterized by continuous growth.

Volatile Organic Compounds in Exhaled Breath, Blood, and Urine Detected in Patients with Thyroid Carcinoma Using Gas Chromatography-Ion Mobility Spectrometry- A Pilot Study.

Background&#xD;Distinguishing between malignant and benign thyroid nodules remains a significant challenge for clinicians and researchers globally. The use of volatile organic compounds (VOCs) has emerged as a novel approach in cancer diagnosis. This prospective pilot study aims to identify VOCs in exhaled breath, blood, and urine that can differentiate benign from malignant thyroid nodules using gas chromatography-ion mobility spectrometry (GC-IMS).&#xD;Methods&#xD;Patients with thyroid nodules scheduled for surgery were enrolled at the Maastricht University Medical Center (MUMC+). Breath samples were analyzed using a BreathSpec GC-IMS machine (G.A.S. Dortmund, Germany), specifically designed for breath analysis. All blood and urine samples were analyzed with a separate GC-IMS device, the FlavourSpec® (G.A.S., Dortmund, Germany).&#xD;Results &#xD;In this proof-of-concept study, 70 patients undergoing thyroid surgery at MUMC+ were consecutively included. Of these patients, 29 were confirmed to have thyroid cancer after surgical resection. The overall analysis did not reveal statistically significant differences in VOCs in breath, urine and blood, between patients with benign and malignant thyroid cancer. &#xD;Conclusion&#xD;This proof-of-concept study demonstrated that GC-IMS was unable to adequately distinguish between the VOC profiles of malignant and benign thyroid nodules. However, this study had a small sample size and future larger studies are needed to investigate the potential of using VOCs to distinguish between benign and malignant thyroid nodules. Furthermore, future research should focus on investigating potential confounders that affect patient VOC profiles.&#xD;(NCT04883294)&#xD.

The Current Progress of Artificial Intelligence in Approach to Thyroid Nodules: A Narrative Review

Background: Artificial intelligence (AI) can play a significant role in the future of thyroidology. Thyroid nodules are common conditions that may benefit from AI through more accurate and efficient diagnosis, risk stratification, and medical or surgical management. Objective: This paper aims to review the latest developments in AI applications for diagnosing and managing thyroid nodules and cancers. Methods: English full-text articles published in the PubMed and Google Scholar databases from January 2014 to March 2024 were collected and reviewed to provide a comprehensive understanding of the topic. A total of 45 studies were selected based on relevance, robust methodology, statistical significance, and broader topic coverage. Results: Artificial intelligence has emerged as a powerful tool for managing thyroid nodules. First, several studies have demonstrated how AI-powered ultrasound interpretation enhances the diagnosis and classification of nodules while reducing the need for invasive fine-needle aspiration (FNA) biopsies. Second, AI significantly improves the cytopathological differentiation between benign and malignant thyroid nodules by minimizing reliance on pathologists' expertise and implementing standardized diagnostic criteria. When cytopathology is inconclusive, AI also aids in identifying molecular markers from omics data, distinguishing between normal and cancerous cells. Moreover, AI tools have been developed for prognosis assessment, predicting distant metastasis, recurrence, and surveillance by integrating medical imaging features with molecular and clinical factors. Additionally, some AI tools are designed for intraoperative evaluation, improving surgical techniques and reducing complications during thyroidectomy. In non-surgical treatments, several models have been developed to optimize therapeutic doses of radioactive iodine (RAI) and predict the outcomes of new drug formulations. Conclusions: Artificial intelligence has the potential to assist physicians in accurate thyroid nodule diagnosis, classification, decision-making, optimizing treatment strategies, and improving patient outcomes. However, there are still limitations to this technology. Artificial intelligence-driven tools require further advancements before they can be fully integrated into clinical practice and replace specialists.

3D ultrasound guidance for radiofrequency ablation in an anthropomorphic thyroid nodule phantom

BackgroundThe use of two-dimensional (2D) ultrasound for guiding radiofrequency ablation (RFA) of benign thyroid nodules presents limitations, including the inability to monitor the entire treatment volume and operator dependency in electrode positioning. We compared three-dimensional (3D)-guided RFA using a matrix ultrasound transducer with conventional 2D-ultrasound guidance in an anthropomorphic thyroid nodule phantom incorporated additionally with temperature-sensitive albumin.MethodsTwenty-four phantoms with 48 nodules were constructed and ablated by an experienced radiologist using either 2D- or 3D-ultrasound guidance. Postablation T2-weighted magnetic resonance imaging scans were acquired to determine the final ablation temperature distribution in the phantoms. These were used to analyze ablation parameters, such as the nodule ablation percentage. Further, additional procedure parameters, such as dominant/non-dominant hand use, were recorded.ResultsNonsignificant trends towards lower ablated volumes for both within (74.4 ± 9.1% (median ± interquartile range) versus 78.8 ± 11.8%) and outside of the nodule (0.35 ± 0.18 mL versus 0.45 ± 0.46 mL), along with lower variances in performance, were noted for the 3D-guided ablation. For the total ablation percentage, 2D-guided dominant hand ablation performed better than 2D-guided non-dominant hand ablation (81.0% versus 73.2%, p = 0.045), while there was no significant effect in the hand comparison for 3D-guided ablation.Conclusion3D-ultrasound-guided RFA showed no significantly different results compared to 2D guidance, while 3D ultrasound showed a reduced variance in RFA. A significant reduction in operator-ablating hand dependence was observed when using 3D guidance. Further research into the use of 3D ultrasound for RFA is warranted.Relevance statementUsing 3D ultrasound for thyroid nodule RFA could improve the clinical outcome. A platform that creates 3D data could be used for thyroid diagnosis, therapy planning, and navigational tools.Key PointsTwenty-four in-house-developed thyroid nodule phantoms with 48 nodules were constructed.RFA was performed under 2D- or 3D-ultrasound guidance.3D- and 2D ultrasound-guided RFAs showed comparable performance.Real-time dual-plane imaging may offer an improved overview of the ablation zone and aid electrode positioning.Dominant and non-dominant hand 3D-ultrasound-guided RFA outcomes were comparable.Graphical

Efficacy of echolaser smart interface-guided laser ablation in volume reduction of symptomatic benign thyroid nodules.

The management of benign symptomatic thyroid nodules until recent years has been limited to surgery, radioactive iodine treatment, or surveillance which is associated with the burden of morbidity of complications or symptom non-relief as well as cost. Laser ablation has emerged as a minimally invasive alternative, this uses laser energy to thermally ablate nodule tissue, leading to volume reduction and symptom relief. Long-term treatment response data is growing but remains limited in the United States. Our study aims to quantify the effectiveness of laser ablation in reducing the volume of thyroid nodules over a 12 to 18-month period. Retrospective review of data was conducted for 63 adults with cytologically benign, solid symptomatic thyroid nodules ranging from 1.333 cm3 to 103.794 cm3 in volume. Ultrasound-guided laser thermal ablation was performed on all nodules using EchoLaser X4 Smart Interface device with 1064 nm diode laser to deliver total ablation energy (joules), calculated per device guidelines. Serial sonographic volume measurements were conducted 1 month, 3 -6 months, 6 - 12 months, and 12 to 18 months post-ablation intervals. Study cohort was comprised of 63 thyroid nodules. reduction in nodule volume increased progressively over time, with median reductions of 46.05% [STD 21.8] at 1 month, 60.33% [STD 20.1] at 3-6 months, 68.69% [STD 18.8] at 6-12 months, and 64.04% [STD 19.27] at 12-18 months. A total of 62, 56, 42, and 17 nodules had available data for analysis at these respective intervals. This study demonstrated a marked progressive reduction of thyroid nodule volume following ablation. The treatment appears to be consistently effective in reducing symptoms across a wide range of nodule sizes, although the degree of volume reduction varies. The results of our study underscore the potential of laser ablation as a viable treatment option for thyroid nodules, with a sustained reduction in nodule volume observed over an extended post-procedure period.

Improving the diagnostic strategy for thyroid nodules: a combination of artificial intelligence-based computer-aided diagnosis system and shear wave elastography.

Thyroid nodules are highly prevalent in the general population, posing a clinical challenge in accurately distinguishing between benign and malignant cases. This study aimed to investigate the diagnostic performance of different strategies, utilizing a combination of a computer-aided diagnosis system (AmCAD) and shear wave elastography (SWE) imaging, to effectively differentiate benign and malignant thyroid nodules in ultrasonography. A total of 126 thyroid nodules with pathological confirmation were prospectively included in this study. The AmCAD was utilized to analyze the ultrasound imaging characteristics of the nodules, while the SWE was employed to measure their stiffness in both transverse and longitudinal thyroid scans. Twelve diagnostic patterns were formed by combining AmCAD diagnosis and SWE values, including isolation, series, parallel, and integration. The diagnostic performance was assessed using the receiver operating characteristic curve and area under the curve (AUC). Sensitivity, specificity, accuracy, missed malignancy rate, and unnecessary biopsy rate were also determined. Various diagnostic schemes have shown specific advantages in terms of diagnostic performance. Overall, integrating AmCAD with SWE imaging in the transverse scan yielded the most favorable diagnostic performance, achieving an AUC of 72.2% (95% confidence interval (CI): 63.0-81.5%), outperforming other diagnostic schemes. Furthermore, in the subgroup analysis of nodules measuring <2 cm or 2-4 cm, the integrated scheme consistently exhibited promising diagnostic performance, with AUCs of 74.2% (95% CI: 61.9-86.4%) and 77.4% (95% CI: 59.4-95.3%) respectively, surpassing other diagnostic schemes. The integrated scheme also effectively addressed thyroid nodule management by reducing the missed malignancy rate to 9.5% and unnecessary biopsy rate to 22.2%. The integration of AmCAD and SWE imaging in the transverse thyroid scan significantly enhances the diagnostic performance for distinguishing benign and malignant thyroid nodules. This strategy offers clinicians the advantage of obtaining more accurate clinical diagnoses and making well-informed decisions regarding patient management.

8414 Utilization of Cell Free DNA Integrity Index to Differentiate Benign from Malignant Thyroid Nodules

Abstract Disclosure: S. Tarafdar: None. S. Dutta: None. P. Mukhopadhyay: None. N.P. Bhattacharya: None. S. Ghosh: None. Introduction: Recent advances in molecular genetics have evaluated a potential role for plasma cell-free DNA (cfDNA) integrity index as a non-invasive cancer marker. Data on cfDNA integrity in differentiated thyroid cancer is sparse and needs to be investigated further. Aim of the study: The purpose of this study is to investigate the hypothesis that longer DNA strands in plasma may serve as a marker for thyroid cancer. Methods: Patients presenting with thyroid nodules underwent ultrasonography with Thyroid Image Reporting and Data Systems (TIRADS) scoring and FNAC (Bethesda classification).Patients with Bethesda 3, 4, 5, and 6 had surgery and confirmation by histopathology. Patients with Bethesda 2 presenting with compressive symptoms and cosmetic concerns underwent surgery; the remaining patients were considered benign based on clinical follow-up, USG, and FNAC characteristics. Blood sample collected prior to FNAC was used to extract and quantify cfDNA. To assess the integrity index 180/67, 306/67, and 476/67 for the APP gene, we used a quantitative real-time PCR (qPCR) method based on the quantification of four amplicons of varying lengths (67, 180, 306, and 476 bp, respectively). Because culture cells had extremely intact genomic DNA, the genomic DNA obtained from the MDA-T32 papillary thyroid cancer cell line was utilised as a reference to estimate the relative DNA strand integrity in plasma DNA. To determine the (ΔCt) value for 67,180, 306, and 476 bp, the Ct value of the sample was subtracted from that of the MDA-T32 control. Results: A total of 161 subjects were recruited, of these 92 were benign and 69 had differentiated thyroid cancer(confirmed by histopathology). Using the 180/67 bp integrity index benign thyroid nodule patients had significant lower value (median 0.39, 95% CI: 0.33-0.46) compared to patients with differentiated thyroid cancer (median 0.62, 95% CI: 0.56-0.68). A cfDNA integrity index of 180/67 bp could significantly differentiate between benign and malignant thyroid nodules (P&amp;lt;0.001). However, there was no significant difference between malignant and benign thyroid nodules based on the cell free DNA integrity indexes of 306/67 and 476/67. Conclusions: The cfDNA integrity score of 180/67 exhibits potential as a circulating marker for the detection of thyroid nodules and as a means of monitoring cfDNA fragmentation in patients with thyroid cancer. However, further confirmation through prospective trials is necessary. Presentation: 6/3/2024

8414 Utilization Of Cell Free DNA Integrity Index To Differentiate Benign From Malignant Thyroid Nodules

Abstract Disclosure: S. Tarafdar: None. S. Dutta: None. P. Mukhopadhyay: None. N.P. Bhattacharya: None. S. Ghosh: None. Introduction: Recent advances in molecular genetics have evaluated a potential role for plasma cell-free DNA (cfDNA) integrity index as a non-invasive cancer marker. Data on cfDNA integrity in differentiated thyroid cancer is sparse and needs to be investigated further. Aim of the study: The purpose of this study is to investigate the hypothesis that longer DNA strands in plasma may serve as a marker for thyroid cancer. Methods: Patients presenting with thyroid nodules underwent ultrasonography with Thyroid Image Reporting and Data Systems (TIRADS) scoring and FNAC (Bethesda classification).Patients with Bethesda 3, 4, 5, and 6 had surgery and confirmation by histopathology. Patients with Bethesda 2 presenting with compressive symptoms and cosmetic concerns underwent surgery; the remaining patients were considered benign based on clinical follow-up, USG, and FNAC characteristics. Blood sample collected prior to FNAC was used to extract and quantify cfDNA. To assess the integrity index 180/67, 306/67, and 476/67 for the APP gene, we used a quantitative real-time PCR (qPCR) method based on the quantification of four amplicons of varying lengths (67, 180, 306, and 476 bp, respectively). Because culture cells had extremely intact genomic DNA, the genomic DNA obtained from the MDA-T32 papillary thyroid cancer cell line was utilised as a reference to estimate the relative DNA strand integrity in plasma DNA. To determine the (ΔCt) value for 67,180, 306, and 476 bp, the Ct value of the sample was subtracted from that of the MDA-T32 control. Results: A total of 161 subjects were recruited, of these 92 were benign and 69 had differentiated thyroid cancer(confirmed by histopathology). Using the 180/67 bp integrity index benign thyroid nodule patients had significant lower value (median 0.39, 95% CI: 0.33-0.46) compared to patients with differentiated thyroid cancer (median 0.62, 95% CI: 0.56-0.68). A cfDNA integrity index of 180/67 bp could significantly differentiate between benign and malignant thyroid nodules (P&amp;lt;0.001). However, there was no significant difference between malignant and benign thyroid nodules based on the cell free DNA integrity indexes of 306/67 and 476/67. Conclusions: The cfDNA integrity score of 180/67 exhibits potential as a circulating marker for the detection of thyroid nodules and as a means of monitoring cfDNA fragmentation in patients with thyroid cancer. However, further confirmation through prospective trials is necessary. Presentation: 6/3/2024

8751 Radiofrequency Thermal Ablation in 32 Patients with Toxic Adenomas with Resolution of Hyperthyroidism in All Cases

Abstract Disclosure: L.G. Amato: None. E.M. Volpi: None. L.D. Volpi: None. P.M. Carani: None. A. Rahal: None. Introduction: In the general population, thyroid nodules are found in 3-7% of individuals on physical examination and in 20-76% on ultrasound. Around 8-10% of benign nodules may present autonomous behavior, being called hot nodules, causing symptoms of hyperthyroidism and being called toxic adenomas (TA). In TAs, autonomous hormone production can be caused by somatic activating mutations of genes regulating thyroid growth and hormone synthesis caused by somatic activating mutations of genes regulating thyroid growth and hormone synthesis. Classically, the proposed treatment for autonomous nodules was surgical resection or radioiodine ablation (RAI). In this context, the prevalence of hypothyroidism after the procedure varies from 2% to 3% following lobectomy, and lower after isthmusectomy in the unique circumstance in which the TA is confined to the thyroid isthmus. A study following 684 patients with TA treated with RAI reported a progressive increase in overt and sub-clinical hypothyroidism. Potential complications following near-total/total thyroidectomy include the risk of permanent hypoparathyroidism (&amp;lt; 2.0%) or recurrent laryngeal nerve injury (RLN) (&amp;lt; 2.0%). A small risk of permanent RLN injury exists with surgery for TA. Following RAI therapy, there have been reports of new-onset Graves Disease (up to 4% prevalence) as well as concern for thyroid malignancy and a very minimal increase in late non thyroid malignancy. Radiofrequency ablation (RFA) has been a precise and effective alternative for the treatment of many benign thyroid nodules over the past ten years, including hot nodules. RFA could preserves normal thyroid function compared to surgery or RAI. Clinical case: We evaluated the effectiveness of a single session of RFA in 32 patients with TA, through hormonal status, achieving normalization of thyroid and volumetric reduction of the nodule. Among the 32 patients included in this study, aged between 25 and 88 years, of these, 31 were women and 1 was a man, all of whom underwent a single RFA procedure (“moving shot” technique associated with hydrodissection). We had a single case of a reversible complication: a patient who had transient vocal cord paralysis, with total reversal. There was a reduction in the volume of all nodules as well as all patients progressed to a state of euthyroidism within 60 days of follow-up. Conclusion: A single session of RFA was effective in treating autonomous nodules, restoring euthyroidism in all patients. Presentation: 6/3/2024

8385 Coexistence of Parathyroid Adenoma &amp; Papillary Thyroid Cancer: A Rare Case Report

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. M. Roy: None. S. Rathore: None. Prevalence of primary hyperparathyroidism (pHPT) ranges from 0.1- 0.4% in general population. Nodular thyroid disease is an increasingly common incidental diagnosis due to widespread use of ultrasound. Papillary thyroid cancer (PTC) is the most common cancer of thyroid gland. Here we report a 53 year old post-menopausal woman presented with weight loss, generalised body aches, arthralgia, myalgia, and proximal muscle weakness. She was hypertensive and clinically euthyroid. Physical examination revealed generalized tenderness all over the body but no thyroid or parathyroid nodules on palpation. Biochemical evaluation showed hypercalcemia 12.1mg/dl (8.4-10.2mg/dl), PTH&amp;gt;2000pg/ml (14-72pg/ml), ALP-1855 U/L (40–125 U/L), decreased phosphorous of 2.4mg/dl (25-4.6 mg/dl), and vitamin-D of 46 nmol/L ( 75-250 nmol/L). USG neck revealed a heterogeneous lesion at the lower pole of right lobe of thyroid gland &amp; two small hypoechoic nodules seen in the right lobe of thyroid gland. FNAC from nodules was inconclusive. USG abdomen revealed nephrocalcinosis. DEXA scan showed severe osteoporosis. Tc99mSestamibi SPECT-CT showed uptake at lower pole of right lobe of thyroid. On exploration, two nodules were palpated in the right lobe of the thyroid and simultaneous right hemi-thyroidectomy was performed. Histopathologic report confirmed parathyroid adenoma (figure 1) as well as presence of carcinoma in the two nodules: one was a papillary thyroid cancer (Classic variant) and the other a follicular variant of papillary thyroid carcinoma (figure 2). Margins were negative for malignancy. She was treated with levothyroxine to maintain TSH &amp;lt;0.1U/L and followed up with annual ultrasound screening. At 2 year follow up, patient was symptom free with improved T score on DEXA scan and no nodule over residual thyroid gland. Discussion: Co-existence of pHPT and PTC ranges from 2.3-4.3%. The use of ultrasound neck as a routine imaging modality for localisation of parathyroid adenoma allows detection of thyroid nodules. Benign and/or malignant thyroid nodules are commonly seen in patients with pHPT and this can range from 2-15%. Women have higher risk for co-existence. The relationship between the two diseases is thought to be incidental. Some authors have suggested possible role of shared genes, embryological factors, transcription factors, vitamin-D deficiency and hyperparathyroidism that could lead to activation of angiogenic factors and carcinogenesis. Fig. 1. Parathyroid adenoma. (a)Tc99m sestamibi scan showing right inferior parathyroid adenoma (b) Parathyroid adenoma (400x high power) comprising predominantly of Chief cells with mild pleomorphism. Fig. 2. Histopathology of PTC. (a)Papillary Carcinoma thyroid. 10xPhotomicrograph showing areas of calcification. (b) Papillary Carcinoma thyroid. Photomicrograph showing thyroid with papillary pattern with areas of infiltration. Presentation: 6/1/2024

8373 High suspicion for thyroid cancer in patient with thyroid Hemiagenesis

Abstract Disclosure: L. Aoun: None. S. Almardini: None. M. Anise: None. F. Haddadin: None. F. Saliba: None. J. Zaidan: None. Background: Thyroid Hemiagenesis (THA) is a rare condition characterized by congenital absence of one lobe of the thyroid gland. Notably, THA is more prevalent in females and the left lobe is more likely to be absent with or without the isthmus. Most patients are euthyroid, and diagnosis is usually incidental, so the true prevalence of THA is uncertain as there are certainly undiagnosed cases. Studies have shown a link between THA, thyroid cancer, and hyperparathyroidism. We present a case of THA and high suspicion for thyroid cancer. Case Presentation: 54-year-old female with history of Rheumatoid arthritis who presented for evaluation of incidental thyroid nodules, occasional palpitations, tremors, and mild change in her voice. She denied abnormal weight loss or diarrhea. No history of radiation to the neck and no family history of thyroid disease or thyroid cancer. The thyroid exam showed an enlarged left palpable nodule. Labs significant for TSH 1.6 mIU/L (normal: 0.4-4 mIU/L), FT4 0.8 ng/dl (normal 0.7-1.9 ng/dL) and T3 77ng/dL (normal: 60-180 ng/dL). Thyroid U/S showed left hemiagenesis and right sided nodules biggest is 1.1 cm solid, hypoechoic with coarse calcifications, FNA was recommended and showed follicular lesion of undetermined significance, molecular testing was done and Thyroseq came back intermediate to high risk RAS and EIF1AX positive reflecting a 70 % probability of cancer. Based on these results, surgery was recommended, and the patient underwent right thyroidectomy. Surgery was uncomplicated and despite reported higher risk of hyperparathyroidism patient’s calcium and PTH were normal, and no parathyroid adenomas were identified intraoperatively. The pathology from the thyroidectomy showed follicular adenoma of 1 cm and no malignancy. She was started on Synthroid 100mcg daily post op. Discussion: This case demonstrates a case of a benign thyroid nodule and preserved parathyroid levels in the setting of thyroid hemiagenesis. Usually in THA, the contralateral lobe is at an increased risk for pathology of compensatory hypertrophy or hyperplasia. According to available studies, cancer association with THA was more common in left hemiagenesis and parathyroid adenomas more common ipsilateral to hemiagenesis . Despite Our patient’s FNA revealed atypical findings, molecular testing revealed RAS and EIF1AX positive, marking intermediate to high cancer risk. However, the thyroidectomy pathology report unveiled no evidence of malignancy, contraindicating the anticipated high cancer risk in those with left THA. This case highlights the rarity of THA and different possible presentations and cancer risks. Presentation: 6/2/2024

7847 Radiomic Ultrasound Checkup of Thyroid Nodules Before Radiodiodine Therapy

Abstract Disclosure: A.A. Trukhin: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). A.V. Manaev: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). S.M. Zakharova: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). M.S. Sheremeta: None. E.A. Troshina: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). Background: Over 83 years radioiodine therapy (RIT) of autonomous thyroid nodules still have uncovered pages, according to its complexity and thyroid nodules variety. There are two main criteria to allow RIT – no malignancy and presence of iodine uptake, the last one could be checked by Tc-99m-pertachnetate or I-123, I-131 iodine scintigraphy. Case with thyroid nodules first undergo ultrasound (US) TI-RADS classification, then fine needle aspiration stratification according to the Bethesda system. Publications applied such algorithm shows 75-85% accuracy in malignancy determination, that in 15-25% can lead to improper RIT application. Aim: Method development for thyroid nodules ultrasound checkup before I-131 administration and I-131 24h uptake prognosis. Methods: Study includes 150 nodules (65 benign, 60 malignant, 25 autonomous benign thyroid nodules). Both US longitudinal and transversal thyroid nodule projections were obtained via GE Voluson E8 (36% benign cases / 27% malignant cases) and GE Logiq E (64% benign cases / 73% malignant cases) in cinematic loop regime. Autonomous thyroid nodules underwent I-131 pharmacokinetics examination with 24h uptake determination and RIT. Statistical textural features were obtained through spatial adjacency matrix. Results: Analysis of 16 statistical textural features shows weak correlation between 11 statistical textural features E (Energy), S (Entropy), LU (Local homogeneity), MP (Maximum probability), TR (Matrix trace), CORR (Correlation), IMC (information measure of correlation), DV (Difference variance), DE (Difference entropy), SE (Sum entropy), SA (Average value of the sum). ROC-analysis using 11 statistical textural features shows the best model for benign/malignance determination with AUC = 0.83, Se = 74%, Sp = 73%, PPV = 75%, NPV = 72%, Acc = 74%. I-131 pharmacokinetics examination shows strong correlation SA to I-131 24h uptake. Conclusions: The performed study demonstrates the possibility of using textural statistical features of ultrasound images as instrument for thyroid nodules ultrasound checkup before I-131 administration, for extra FNA prescription and prognosis the I-131 24h important in exact therapeutic I-131 activity calculation. Presentation: 6/2/2024