Search Results (273)

Background/Objectives: Thyroid nodules are commonly found through sensitive imaging methods like ultrasonography. While most nodules are benign and asymptomatic, certain characteristics may indicate malignancy, prompting fine needle aspiration biopsy. Factors like age and gender affect cancer risk, complicating ultrasound-based risk systems. We aimed to determine whether the cytological malignancy rate of thyroid nodules could be adjusted for several clinical parameters. Methods: Data from patients aged 18 and above with thyroid nodules assessed via fine needle aspiration (FNA) were retrospectively reviewed. Malignancy classification was based on cytopathology and histopathology results. The study examined how various clinical parameters, adjusted for the ACR TI-RADS category, affected thyroid nodule malignancy rates, including age, sex, Body Mass Index (BMI), nodule size, presence of autoimmunity, and thyroxine therapy. Additionally, we analyzed the performance of ACR TI-RADS in predicting malignant cytology across different age subgroups of thyroid nodules. Results: The study included 1128 thyroid nodules from 1001 adult patients, with a median age of 48 years and predominantly female (76.68%). Malignancy rates varied across ACR TI-RADS categories, with higher rates associated with larger nodules and younger age groups. Age emerged as a significant predictor of malignancy, with a consistent decrease in the odds ratio for malignant cytology with advancing age across all ACR TI-RADS categories, indicating its potential utility in risk assessment alongside nodule size and sex. Conclusions: Raising the size threshold for recommending FNA of TR3-3 nodules and incorporating patients’ age and gender into the evaluation process could enhance the system’s accuracy in assessing thyroid nodules and guiding clinical management decisions. Full article

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article

Background: Thyroid neoplasms exhibit a diverse molecular landscape, and the 2022 WHO classification emphasizes the critical role of molecular profiling in thyroid cancer management; however, comprehensive mutational data from fine-needle aspiration cytology (FNAC) samples using targeted next-generation sequencing (NGS) are still limited, necessitating further investigation to guide clinical practice. Purpose: To characterize the mutational landscape of thyroid neoplasms using targeted NGS of FNAC samples and to assess the clinical implications of molecular profiling. Materials and Methods: This retrospective study included 952 patients with thyroid carcinomaneoplasms who underwent surgery at Sun Yat-sen Memorial Hospital from 2021 to 2023. Preoperative ultrasound, FNAC, and targeted NGS were performed. NGS panels covering 18, 88, and pan-cancer genes were used to analyze FNAC samples. Molecular alterations were correlated with clinical and pathological features. Results: The most frequent mutation was BRAF^V600E (84.45%), followed by RET (6.41%), BRCA1/2 (4.41%) and RAS (4.41%). Patients were categorized into BRAF-like (830 cases), RAS-like (36 cases), high-risk mutations (25 cases), and other mutations (28 cases). High-risk mutations were associated with older age and larger tumor size. BRAF-like tumors had a higher lymph node metastasis rate (58.77%) compared to RAS-like tumors (33.33%). Tumor mutation burden varied significantly among different thyroid neoplasm subtypes. Conclusions: Molecular profiling using targeted NGS of FNAC samples provides valuable insights into the genetic landscape of thyroid neoplasms and has significant clinical implications for diagnosis and personalized treatment strategies. Further validation with paired tumor and plasma samples is warranted. Full article

Background: The prognosis management of thyroid cancer remains a significant challenge. This study highlights the critical role of T cells in the tumor microenvironment and aims to improve prognostic precision by integrating bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data, providing a more comprehensive view of tumor biology at the single-cell level. Method: 15 thyroid cancer scRNA-seq samples were analyzed from GEO and 489 patients from TCGA. A multi-level attention graph neural network (MLA-GNN) model was applied to integrate T-cell-related differentially expressed genes (DEGs) for predicting disease-free survival (DFS). Patients were divided into training and validation cohorts in an 8:2 ratio. Result: We systematically characterized the immune microenvironment of metastatic thyroid cancer by using single-cell transcriptomics and identified the important role of T-cell subtypes in the development of thyroid cancer. T-cell-based DEGS between tumor tissues and normal tissues were also identified. Subsequently, T-cell-based risk signatures were selected for establishing a risk model using MLA-GNN. Finally, our MLA-GNN-based model demonstrated an excellent ability to predict the DFS of thyroid cancer patients (1-year AUC: 0.965, 3-years AUC: 0.979, and 5-years AUC: 0.949 in training groups, and 1-year AUC: 0.879, 3-years AUC: 0.804, and 5-years AUC: 0.804 in validation groups). Conclusions: Risk features based on T-cell genes have demonstrated the effectiveness in predicting the prognosis of thyroid cancer. By conducting a comprehensive characterization of T-cell features, we aim to enhance our understanding of the tumor’s response to immunotherapy and uncover new strategies for the treatment of cancer. Full article

Background: Lenvatinib is a receptor tyrosine kinase inhibitor indicated for advanced radioiodine-refractory thyroid cancer (RAI-RTC). It is recommended to start at 24 mg per day; however, in patients who are at risk of severe adverse events, it may be reasonable to start at lower doses. Patients and Methods: We included 15 patients with RAI-RTC who started lenvatinib at a very low/low dose and evaluated the efficacy and safety. Results: Eight patients (53.3%) did not show progression of the disease, and about half of the patients (53.3%) were alive at the last follow-up visit. Up to 26.6% of patients achieved a partial response to therapy, with a notable volume reduction in the local and metastatic lesions. However, 80% of patients experienced adverse events, mainly of a moderate grade. Conclusions: Although these findings are based on a small sample size and a single-center study, treatment with lenvatinib at very low/low doses in fragile patients seems to be a promising strategy for the management of RAI-RTC, balancing effective disease control with a favorable safety profile. Full article

Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques that are most commonly used are thyroid hormone withdrawal (THW), which induces endogenous TSH elevation by creating a hypothyroid state, and exogenous stimulation with recombinant human TSH (rhTSH). This review compares both approaches over a range of DTC risk categories. Extensive evidence demonstrates that rhTSH and THW yield equivalent oncological outcomes, including remnant ablation success, recurrence-free survival, and overall survival, in low-, intermediate-, and high-risk disease. Additionally, rhTSH maintains quality of life by avoiding hypothyroid symptoms. While THW continues to be an excellent option when there is a lack of availability of rhTSH, its disadvantages, particularly the transient hypothyroid state, must be carefully weighed against the demonstrated equivalence in efficacy. In current clinical practice, rhTSH is frequently the preferred option for its convenience, safety, and patient-centered benefits; however, the selection of the optimal approach should be based on individual clinical circumstances and patients’ preferences, as well as resource considerations. Full article

Radioactive iodine therapy has been a well-established treatment for various thyroid conditions since the 1940s, targeting both benign diseases and malignancies. Treatment for benign conditions typically involves low doses of 131I, often requiring no more than two treatments, with the dose either fixed or personalized based on thyroid tissue mass and iodine uptake. In contrast, differentiated thyroid cancer treatment often requires higher doses and multiple administrations, especially for metastatic cases. Recent guidelines and studies have proposed more conservative management strategies, including careful follow-up, due to concerns over the high risk–benefit ratio in selected cases with a low risk of disease recrudescence. Despite its possible efficacy, radioiodine therapy is associated with dose-dependent side effects, the most common of which is salivary gland dysfunction or inflammation, affecting approximately 30% of adult patients. These effects pose significant challenges in nuclear medicine practice. This review aims to summarize the latest evidence on the incidence, impact on quality of life, prevention strategies and the role of these side effects in the decision-making process regarding RAI therapy. Full article

Therapy with radioactive iodine (I-131) following a total thyroidectomy has been a gold standard in the treatment of differentiated thyroid cancer (DTC) for over 80 years. Over the years, its role has shifted from routine use to a more selective, risk-adapted approach, informed by tumor biology, patient risk stratification and evolving clinical guidelines. This review examines the changing landscape of I-131 therapy, tracing its historical foundations, current indications, and future directions shaped by molecular medicine. We discuss the transition from a standardized, one-size-fits-all treatment approach to an individualized, dynamic stratification model that allows for ongoing risk reassessment and tailored treatment strategies. Key updates in clinical practice, such as the 2015 ATA Guidelines, the 2022 ETA Consensus Statement, and joint SNMMI and EANM nuclear medicine recommendations, are critically examined. We also address ongoing controversies in the management of low- and intermediate-risk patients, including the roles of I-131 whole-body scanning, activity selection, and overall treatment approach. Molecular theranostics is ushering in a new era in DTC management, enabling improved patient selection and more precise treatment. Advances in molecular profiling, imaging, and targeted therapies support a personalized treatment approach that aims to optimize therapeutic decisions while minimizing side effects and enhancing long-term safety. Full article

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

Objectives: The current standard of care for endocrine tumors includes a personalized diagnostic and therapeutic approach aimed at the early detection of tumor recurrence after radical surgery. Assessment of tumor-associated biological factors in serum may be useful in patient management. The aim of this study is to determine whether any of the selected growth factors (VEGF, FGF), lectins (Galectin-1, Galectin-3), proteins (Fascin), or TNF-α measured in serum may serve as a potential marker of recurrence. Methods: A total of 68 cases, including 43 patients with disseminated endocrine neoplasm (neuroendocrine tumor (NET) 30 cases, medullary thyroid cancer (MTC) 6 cases, adrenal neoplasm 7 cases) and 25 healthy participants, were included in the analysis. Serum concentrations of TNF-α, Fascin, VEGF, Galectin-1, Galectin-3, and FGF were determined in all cases. The results were compared between groups. Results: A comparison between all patients and controls revealed differences in TNF-α concentrations (2.88 vs. 0.93 (ng/mL), p = 0.008). When comparing the concentrations of the measured factors between the subgroups (classified by tumor type) and the control group, differences were found for TNF-α (p = 0.007) and Fascin (p = 0.035). In the case of Fascin, differences were found for MTC and adrenal neoplasm patients (0.52 vs. 5.28 (ng/mL), p = 0.048), as well as MTC and NET patients (0.52 vs. 5.59 (ng/mL), p = 0.007), while the differences between NET patients and controls were close to significance (5.59 vs. 3.67 (ng/mL), p = 0.076). For TNF-α, significant differences were found between NET patients and controls (2.88 vs. 0.03 (ng/mL), p = 0.005) as well as between MTC patients and controls (2.77 vs. 0.93 (ng/mL), p = 0.004). Conclusions: Serum concentrations of selected proteins and growth factors (Fascin, TNF-α) are significantly higher in those with disseminated endocrine tumors compared to healthy controls. More studies are needed to determine the role of these selected proteins and growth factors in the early detection of NET/MTC recurrence. Full article

Background: Assessing cancer survival trends is crucial for monitoring progress in cancer management and prevention. As part of the broader HUN-CANCER EPI study, this analysis examined overall survival (OS) in the Hungarian cancer population between 2011 and 2019. Methods: Using data extracted from the Hungarian National Health Insurance Fund (NHIF) database, short- and long-term OS were estimated for various cancer types according to age, sex, and diagnostic period using Kaplan–Meier analysis. The study also identified cancer types with significant early mortality following diagnosis. Results: From 2011 to 2019, a total of 528,808 patients were diagnosed with cancer. During the 2015–2019 diagnostic period, the lowest 5-year OS rates were observed for esophageal (7.0%), pancreatic (10.7%), liver (12.5%), gallbladder (13.9%), and lung cancer (18.4%). Conversely, tumor types with better OS included testicular cancer (91.6%), thyroid cancer (89.0%), Hodgkin’s lymphoma (84.0%), melanoma (78.6%), and breast cancer (74.1%). A notable proportion of deaths occurred within 2 months of diagnosis for liver (33.2%), pancreatic (27.9%), and gallbladder cancer (29.0%). Significant early mortality within 6 months post-diagnosis was also noted for esophageal (51.3%), stomach (42.9%), and lung cancer (41.7%). Conclusions: The HUN-CANCER EPI study conducted between 2011 and 2019 provides valuable insights into cancer survival patterns in Hungary, emphasizing the importance of early detection and targeted interventions to improve patient outcomes. Full article

Background: The understanding of the molecular basis of paediatric thyroid carcinoma has expanded rapidly in the last decade. Most carcinomas are associated with de novo somatic gene alterations that confer distinct clinicopathological characteristics. In comparison to adults, paediatric carcinomas are less commonly associated with point mutations and more commonly with gene fusions, which are characterised by more-invasive disease. Cancer predisposition genes play an important role in a small percentage of tumours, and the family history and the recognition of other syndromic features are key to identifying these patients. Molecular testing platforms for clinical use have been developed and validated in adults, and their use is becoming established in the management of indeterminate thyroid nodules, where they significantly reduce the rates of diagnostic lobectomy. Paediatric data are more limited than adult data, and the role of molecular testing in paediatric thyroid carcinoma management is evolving. Methods: This review describes the current knowledge of molecular alterations in paediatric thyroid carcinomas, evidence supporting molecular testing in clinical practice, and future directions for research. Results and Conclusions: A molecular diagnosis enables the use of molecularly targeted therapies for children and adolescents with advanced or radioiodine-refractory disease. There is also great potential for molecular testing to improve the accuracy of the risk-stratification of paediatric thyroid nodules, reducing surgical intervention and complications without negatively impacting outcomes, and data to support such an approach are emerging. Full article

Cowden syndrome (CS) is a rare hereditary disorder characterized by benign overgrowth in various tissues and a high risk of breast and thyroid cancer. CS is closely associated with pathogenic variants (PVs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene. PVs in PTEN are usually inherited and estimates of de novo frequencies remain inconclusive. The diagnosis of PTEN-associated syndromes remains a challenge in clinical practice, due to patients showing seemingly unrelated symptoms. We report on the clinical management of a now 18-year-old female CS patient, who initially presented with macrosomia, motor development delay and later, lipomas on the abdominal wall. Genetic testing revealed a de novo PTEN PV c.1003C>T(p.Arg335X). The PV was detected in leukocyte DNA of the patient. Using direct DNA sequencing, as well as NGS, the PV was not found in any of the tissues derived from immediate family members. However, the PV was detected in multiple samples representing other germ layers of the affected patient, which renders constitutional mosaicism unlikely. This case constitutes the first description of a de novo PTEN PV, in which constitutional mosaicism was systematically ruled out and underscores the importance of timely genetic testing of patients and their relatives. The diagnosis of a PTEN PV in early childhood allows for the implementation of a comprehensive, lifelong care plan that addresses both pediatric and adult medical needs as well as cancer risk surveillance and family planning. This not only accounts for the affected patients, but also their close family members who might be susceptible to the same PV. Full article

Objective: Therapeutic lateral neck dissection is recommended for papillary thyroid cancer with metastatic lymph nodes detected on palpation or on preoperative imaging. Current guidelines recommend systematic dissection of levels IIA, III, IV and VB in these patients. Despite this recommendation, management of level V remains controversial due to a varying degree of clinical and occult lymph node involvement reported in published retrospective studies, but also due to the functional risk involved in level V dissection in which the spinal accessory nerve may be temporarily or permanently injured. The aim of this review was to address the issues involved in level VB dissection and to provide our view of surgical management of level VB. Method: Narrrative review. Result: We propose a new concept of a partial or “super-superselective” level VB dissection in patients with clinical disease in levels IIA, III and IV. Full article

Thyroid Cancer (TC) is one of the most prevalent endocrine malignancies, with early detection being critical for patient management. The motivation for integrating Machine Learning (ML) in thyroid cancer research stems from the limitations of conventional diagnostic and monitoring approaches, as ML offers transformative potential for reducing human errors and improving prediction outcomes for diagnostic accuracy, risk stratification, treatment options, recurrence prognosis, and patient quality of life. This scoping review maps existing literature on ML applications in TC, particularly those leveraging clinical data, Electronic Medical Records (EMRs), and synthesized findings. This study analyzed 1231 papers, evaluated 203 full-text articles, selected 21 articles, and detailed three themes: (1) malignancy prediction and nodule classification; (2) other metastases derived from TC prediction; and (3) recurrence and survival prediction. This work examined the case studies’ characteristics and objectives and identified key trends and challenges in ML-driven TC research. Finally, this scoping review addressed the limitations of related and highlighted directions to enhance the clinical potential of ML in this domain while emphasizing its capability to transform TC patient care into advanced precision medicine. Full article