Marcadores de cáncer stem cells y transición epitelio mesenquimal como factores de agresividad y progresión en pacientes jóvenes con cáncer de tiroides

El cáncer de tiroides (CT) es el primer tumor maligno en glándulas endocrinas, y se estima que al 2030 estará en el top cinco de cáncer a nivel mundial. En Chile, el CT fue incluido, recientemente, como la patología N° 82 con Garantías Explícitas de Salud, lo que implica destinar importantes recursos públicos y privados al tratamiento de pacientes con un cáncer que va en aumento en el mundo. Existen grupos de pacientes jóvenes con tumores pequeños que presentan un comportamiento clínico más agresivo desde el inicio, donde se podría adelantar la toma de decisiones. Específicamente, destaca un grupo de pacientes menores de 55 años con tumores pequeños menores de 2 cm, pero con metástasis regionales, que quedan fuera de la indicación de radioyodoterapia y podrían requerir tratamiento complementario o presentar peor evolución. Las herramientas clínicas y moleculares para guiar el tratamiento adecuado en pacientes con metástasis linfonodales son limitadas y no han sido actualizadas hasta el momento. Existen factores de tumorigenicidad y pronóstico, tales como los marcadores de Transición Epitelio-Mesenquimal (TEM) y Cáncer Stem Cells (CSC) que se han incorporado al estudio de otros tumores y recientemente en cáncer de tiroides. Actualmente estudios que relacionan TEM y CSC con CT apuntan a la descripción molecular y genética, con escasos reportes que correlacionen, clínicamente, estos hallazgos, (particularmente en subgrupos con características particulares de agresividad) y que los propongan como marcadores de tumorigenicidad y pronóstico. La descripción de estos biomarcadores en la población descrita podría facilitar la toma de decisiones en cuanto a seguimiento, terapia quirúrgica y radioyodoterapia.

Thyroid cancer (TC) is the first malignant tumor in endocrine glands, and it is estimated that by 2030 it will be in the top five cancers worldwide. In Chile, TC was recently included as pathology No. 82 with Explicit Health Guarantees, which implies allocating significant public and private resources to the treatment of patients with a cancer that is on the rise. There are groups of young patients with small tumors that present a more aggressive clinical behavior, where decision-making could be advanced. Specifically, a group of patients under 55 years of age with tumors less than 2 cm in size but with regional metastases, that lack indication for radioiodine therapy and could require complementary treatment or present a worse evolution. Clinical and molecular tools to guide appropriate treatment in patients with lymph node metastases are limited and have not been updated. There are tumorigenicity and prognostic factors, such as EpithelialMesenchymal Transition (EMT) and Cancer Stem Cells (CSC) markers that have been incorporated into the study of other tumors and recently in thyroid cancer. Studies linking EMT and CSC with TC currently point to molecular and genetic description, with few reports clinically correlating these findings (particularly in subgroups with particular characteristics of aggressiveness) and proposing them as tumorigenicity and prognosis markers. The description of these biomarkers in the described population could facilitate decision-making regarding follow-up, surgical therapy, and radioiodine therapy.

Thyroid dysfunction due to trace element deficiency-not only selenium but also zinc.

INTRODUCTION: Levels of serum selenium (Se) and zinc (Zn) decrease when total parental nutrition (TPN) is administered without trace element supplementation for just a few weeks. These trace elements are involved in thyroid hormone metabolism and their deficiencies cause thyroid dysfunction. However, there have been few reports on the details of its clinical course. CASE PRESENTATION: A 50-year-old man presented with thyroid dysfunction due to Se and Zn deficiency. He had an approximately 70-cm residual small intestine after undergoing intestinal resection and he received TPN without trace element supplementation for one and a half months. Blood tests revealed high levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) and low levels of free triiodothyronine (FT3). An abnormal pattern of thyroid function led to suspicion of Se deficiency. Se supplementation raised FT3 levels and lowered FT4 levels to within their respective reference ranges; however, subclinical hypothyroidism persisted with transient TSH elevation. We suspected that Zn deficiency also contributed to the hypothyroidism and, therefore, initiated Zn supplementation, which resulted in normalization of thyroid function. DISCUSSION: Although thyroid dysfunction has been reported in many studies conducted on Se and Zn deficiencies, hormonal patterns vary between reports. Further accumulation of cases, including detailed data on nutritional status, would be of benefit to elucidate the clinical reality. CONCLUSION: It is important to consider Se and Zn deficiencies when TSH and FT4 levels are elevated. It should also be noted that transient TSH elevation may be observed with Se supplementation.

Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

Traditional Chinese medicine treatment for benign thyroid nodules: Literature review.

Thyroid nodules (TNs) are pathological changes characterized by abnormal proliferation of thyroid gland tissue. Approximately 19% to 67% of asymptomatic individuals are diagnosed with TNs, with the majority being benign nodules and 4% to 6.5% being thyroid cancer nodules. Western medicine recommends regular examinations and surgery, while traditional Chinese medicine (TCM) provides an alternative choice to maintain thyroid function and reduce the need for surgery. However, in Taiwan, research on TCM treatment for benign TNs is primarily limited to case reports, lacking large-scale and systematic clinical studies. We conducted a search of electronic databases including PubMed, Google Scholar, Wanfang Data, and China National Knowledge Infrastructure to collect clinical trials related to TCM treatment for TNs. Our goal is to provide new treatment options, further validate the value of TCM in the treatment of TNs, and lay a foundation for future clinical research.

Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule on experimental autoimmune thyroiditis in female rats.

OBJECTIVE: To observe the effects of Buzhong Yiqi granule on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis (EAT). METHODS: EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine. Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, selenium yeast (PC) group, low dose Buzhong Yiqi (BZYQ-L) group, medium dose Buzhong Yiqi (BZYQ-M) group and high dose Buzhong Yiqi (BZYQ-H) group. After two months of drug intervention according to dosage, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) in peripheral blood of rats. The pathological changes of rat thyroid tissues were observed under light microscope with HE staining; ELISA was used to determine estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-müllerian hormone (AMH), and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining. RESULTS: Compared with the NC group, BZYQ granule improved the thyroid and ovarian tissue morphology, and the levels of TPOAb, TGAb and TSH in the model group rats significantly increased (P < 0.05), the thyroid tissue was severely destroyed, the levels of E2, FSH, LH, T, AMH significantly increased (P < 0.05), and the ovary exhibited polycystic changes; Compared with the model group, TSH level in the BZYQ-L group rats decreased (P < 0.05), FSH, T, AMH levels decreased (P < 0.05), in the BZYQ-M group TPOAb, TSH levels decreased (P < 0.05), FSH, LH, T, AMH levels significantly decreased (P < 0.05), BZYQ-H group TPOAb, TGAb, TSH levels significantly decreased (P < 0.05), FSH, LH, T, AMH levels significantly decreased (P < 0.05), with the greatest improvement and significantly better than selenium yeast group (P < 0.05). CONCLUSIONS: BZYQ granule could regulate the thyroid function of EAT rats, reduce thyroid antibody titers, then act on the ovarian function, regulate hormone disorders, and alleviate the pathological damage of rat's ovarian tissues. The effect of high dose Buzhong Yiqi granule is the best.

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

BACKGRUOUND: Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. METHODS: We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. RESULTS: A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. CONCLUSION: High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

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

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

A Multi-dimensional Data Mining-based Study on the Prescriptions Developed by Professor Xu Zhiyin in Treating Thyroid Nodules.

OBJECTIVES: In this study, we employed a multi-dimensional data mining approach to examine the clinical instances where Professor Xu Zhiyin treated thyroid nodules. Our aim is to understand the patterns of symptoms, underlying causes, and treatment approaches used for thyroid nodules. By doing so, the intention is to distill the essential aspects, compile Professor Xu Zhiyin's clinical insights, and investigate his scholarly perspectives. METHODS: Professor Xu Zhiyin's clinical diagnoses and treatments spanning from 2009 to 2019 were entered into Microsoft Excel. Subsequently, the collected data was imported into the Medcase V5.2 system to facilitate data mining. Various techniques, such as frequency-based method, association rule analysis, and clustering, including a decentralized system clustering approach, were employed on a set of 346 cases involving patients with thyroid nodules that conformed to the specified criteria. The primary focus was on extracting insights regarding symptoms and the underlying causes from the medical records. By integrating these findings with Professor Xu Zhiyin's clinical expertise, we examined and summarized the outcomes of the data mining process. RESULTS: The fundamental prescriptions were successfully extracted using the techniques for mining across multiple dimensions. Utilizing the scattered grouping of these prescriptions and with reference to the cluster analysis of the frequency-linked system, the fundamental prescriptions proposed by Professor Xu Zhiyin for addressing thyroid nodules encompass the following ingredients: Glycyrrhiza uralensis Fisch, Cortex Moutan, Paeoniae radix rubra, Curcuma longa L., Radix Curcumae, persica seed, Citri Reticulatae Viride Pericarpium, Pinellia ternata, Spica Prunellae, Ostreae concha, Gleditsia sinensis spine, Tuckahoe and Radix Codonopsis. CONCLUSION: The fundamental prescriptions were acquired using the frequency approach, association rule technique, k-means clustering approach, and systematic clustering approach. The research findings corroborate one another, demonstrating that Professor Xu Zhiyin's approach to distinguishing and treating thyroid nodules is embodied in distinct prescriptions tailored to specific diseases.

Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

A Rare Case of Persistent Multifocal Cribriform-Morular Thyroid Carcinoma.

Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

Metabolic Profiles and Blood Biomarkers to Discriminate between Benign Thyroid Nodules and Papillary Carcinoma, Based on UHPLC-QTOF-ESI+-MS Analysis.

In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI+-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination.

Primary Intrathoracic Ectopic Papillary Thyroid Carcinoma, Presenting With Thoracic Spine Metastasis: A Case Presentation and Literature Review.

Thyroid cancer in ectopic thyroid tissue is a very rare entity. We report a patient with papillary thyroid cancer arising from upper mediastinal ectopic thyroid tissue. The patient presented with thoracic spine metastasis with cord compression. The patient was a 67-year-old woman, who presented with upper back pain. Magnetic resonance imaging (MRI) showed suspected metastatic disease in the second and third thoracic vertebrae (T2 and T3). She underwent laminectomy and decompression surgery at the T1-T3 level. The final pathology report showed metastatic thyroid carcinoma with papillary features. She underwent external beam radiation to the affected spine. Computerized tomography (CT) scan of the chest, abdomen, and pelvis showed a 3.0 × 2.8 × 2.3 cm soft-tissue mass in the left superior mediastinum extending into the supraclavicular region. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed hypermetabolic foci in the upper mediastinum. Fine needle aspiration (FNA) of the upper mediastinal mass was consistent with papillary thyroid cancer. Molecular testing from the FNA sample using Thyroseq V3 showed SQSTM1NTRK3 chromosomal rearrangement. A total thyroidectomy was performed. Pathology of the resected thyroid was benign. Pathology of the mediastinal mass showed a papillary thyroid carcinoma with focal tall cell features, forming a 4 × 2.5 × 2.5 cm mass. Surgery was followed by ablation with 100 millicuries (mci) of radioactive iodine (I-131) and external beam radiation. This case highlights the presentation of primary intrathoracic papillary thyroid cancer with SQSTM1-NTRK3 chromosomal rearrangement and the challenges in the diagnosis and management of this unique case. This patient had a very aggressive disease presentation that required multimodal treatment, including thoracic spine decompression, total thyroidectomy, primary intrathoracic goiter resection, high-dose radioactive iodine treatment, and external beam radiation to the affected spine area. SQSTM1-NTRK3 chromosomal rearrangement can be targeted by medications such as larotrectinib and endtrectinib.

The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.

Background: The effect of micronutrients on thyroid cancer has been studied in observational studies, however, the cause of relationships has not yet been determined. Thyroid cancer was the subject of a Mendelian randomization (MR) analysis of micronutrients. Aimed to determine whether micronutrient intake has a causal impact on the chance of developing thyroid cancer. Methods: We used a Mendelian randomization (MR) analysis with two samples. Our circulation levels of Cu, Ir, Zn, Ca, VD, and VC were reflected by genetic variations reported from GWAS in individuals of European ancestry. For the GWAS outcome of thyroid cancer. Sensitivity studies that included MR-Egger, weighted median/mode tests, and a more open selection of variations at a genome-wide sub-significant threshold were added to our inverse-variance weighted (IVW) MR study. Results: Using the IVW approach, we did not find evidence that any of the micronutrients to thyroid cancer (Cu: odds ratio [OR = 0.88, p = 0.41]; Zn: odds ratio [OR = 0.87, p = 0.40]; Ir: odds ratio [OR = 1.18, p = 0.39]; Ca: odds ratio [OR = 1.12, p = 0.43]; VC: odds ratio [OR = 0.95, p = 0.22]; VD: odds ratio [OR = 0.89, p = 0.04]). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. Conclusion: This study does not provide evidence that supplementation with micronutrients including Cu, Ir, Zn, Ca, VD, and VC can prevent thyroid cancer.

Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

Effect of Music Therapy on Pain During Thyroid Fine Needle Aspiration Biopsy; A Randomized Controlled Clinical Trial.

INTRODUCTION: High-resolution ultrasonography devices have led to the increased detection of thyroid nodules and the need for fine-needle aspiration biopsy (FNAB). However, FNAB is an invasive procedure that can cause discomfort and pain. Music therapy has been used for centuries to alleviate pain, and our clinical trial was conducted to investigate its impact on pain scores during thyroid FNAB. MATERIALS AND METHODS: We conducted a randomized, controlled clinical trial, including adult patients undergoing thyroid FNAB. We evaluated the nonpharmacological intervention of listening to music before and during thyroid FNAB. We used a slow, nonlyrical, flowing melody with a tempo of 60 to 80 beats per minute as a therapeutic intervention for managing anxiety and pain. It had low tones, minimal percussion, and a volume of around 60 dB. The Beck Anxiety Inventory and Visual Pain Scale were used. RESULTS: The study included 529 patients assigned to either the music group (n = 258, 48.7%) or the control group (n = 271, 51.2%). The patients were categorized into subgroups based on either a single nodule (73.63%) or multiple nodules (24.18%). When all patients or single nodule and multiple data are examined separately, the intervention group showed statistically significantly lower pain scores than the control group. CONCLUSION: Our study is among the first on this topic and the largest in the available literature to demonstrate that listening to music during FNAB significantly reduces pain and anxiety. Music therapy is an effective, safe, and noninvasive intervention that can improve patient care and reduce distress and pain.

Current evidences in poorly differentiated thyroid carcinoma: a systematic review and subsection meta-analysis for clinical decision making.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) is a distinct entity with intermediate prognosis between indolent follicular thyroid cancers and anaplastic carcinoma. The management guidelines are not standardized for these cancers due its low prevalence and limited available literature. Therefore, we did this systematic review with emphasis on current evidence on diagnosis, imaging, molecular markers, and management of these carcinomas. MATERIALS AND METHODS: We searched four databases, PubMed, Medline, EMBASE, and Emcare to identify studies published till October 2023. All studies reporting diagnostic tests, imaging, molecular marker expression and management of PDTC were included in the review. The meta-analysis was conducted on expression of molecular markers in these cancers following recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Random-effects meta-analysis was used to calculate pooled estimated prevalence with 95% confidence intervals. Based on the inclusion criteria, 62 articles were selected to be incorporated for the review. Differences in pathological diagnostic criteria of PDTC was noted in literature which was addressed in WHO 2022 diagnostic terminologies with expansion of the definition. Surgical management is uniformly recommended for early stage PDTC. However, literature is divided and anecdotal for recommendations on radioactive iodine (RAI), extent of neck dissection and adjuvant treatment in PDTC. Evidence for Next Generation Sequencing (NGS), novel theragnostic approaches, immunotherapy targets are evolving. Based on the subset analysis for expression of molecular markers, we found the most common markers expressed were TERT (41%), BRAF (28%) and P 53 (25%). CONCLUSION: Poorly differentiated thyroid carcinomas have a high case fatality rate (up to 31%). Eighty-five % of the patients who succumb to the disease have distant metastasis. Even though under-represented in literature, evidence-based management of these aggressive tumors can help personalize the treatment for optimal outcomes.

Fear of Cancer Recurrence in Differentiated Thyroid Cancer Survivors: A Systematic Review.

Background: Despite excellent survival rates, health-related quality of life detriments are common in differentiated thyroid cancer survivors and can be driven by fear of cancer recurrence (FCR). This review aims to report the incidence of FCR in thyroid cancer survivors and synthesize evidence regarding contributing factors. An overview and appraisal of the range of tools used to measure FCR is presented. Methods: A systematic review of the English literature was performed. The search across six electronic databases generated 3414 studies. Two reviewers independently screened the citations and full-text articles, of which 31 were included. The data were extracted independently by two reviewers. Results: The incidence of FCR was reported in 27/31 studies and ranged from 15% to 91%. Direct comparisons regarding incidence and severity of FCR were not possible due to heterogeneity in cut-points used to define FCR. A total of eight validated tools were used to measure FCR across all studies, with five studies using self-developed nonvalidated items. There was minimal repetition of validated tools and no clear consensus as to a preferred survey tool. Factors influencing FCR were reported in 11 studies. There was minimal overlap of factors influencing FCR. Risk factors contributing to increased FCR reported in more than one study included young age and an upcoming clinical appointment. Male gender and higher education levels were reported in more than one article as protective. No literature evaluating interventions to address FCR in thyroid cancer survivors was found. Conclusion: FCR is common in thyroid cancer survivors, but significant heterogeneity in the current evidence base limits assessment of incidence, severity, or risk factors. There is a need to use validated tools to assess FCR in both research and clinical contexts. Reliable assessment of FCR may permit routine assessment of FCR in clinical practice and allow interventions to be prospectively evaluated to optimize the holistic well-being of thyroid cancer survivors.

Papillary Thyroid Microcarcinoma: Differences between Lesions in Incidental and Nonincidental Settings-Considerations on These Clinical Entities and Personal Experience.

Papillary thyroid microcarcinoma (PTMC) represents 35-40% of all papillary cancers; it is defined as a nodule ≤ 10 mm at the time of histological diagnosis. The clinical significance of PTMC is still controversial, and it may be discovered in two settings: incidental PTMC (iPTMC), in which it is identified postoperatively upon histological examination of thyroid specimens following thyroid surgery for benign disease, and nonincidental PTMC (niPTMC), in which it is diagnosed before surgery. While iPTMC appears to be related to mild behavior and favorable clinical outcomes, niPTMC may exhibit markers of aggressiveness. We retrospectively review our experience, selecting 54 PTMCs: 28 classified as niPTMC (52%) and 26 classified as iPTMC (48%). Patients with niPTMC showed significant differences, such as younger age at diagnosis (p < 0.001); a lower male/female ratio (p < 0.01); a larger mean nodule diameter (p < 0.001); and a higher rate of aggressive pathological findings, such as multifocality, capsular invasion and/or lymphovascular invasion (p = 0.035). Other differences found in the niPTMC subgroup included a higher preoperative serum TSH level, higher hospital morbidity and a greater need for postoperative iodine ablation therapy (p < 0.05), while disease-free long-term survival did not differ between subgroups (p = 0.331) after a mean follow-up (FU) of 87 months, with one nodal recurrence among niPTMCs. The differences between iPTMC and niPTMC were consistent: patients operated on for total thyroidectomy and showing iPTMC can be considered healed after surgery, and follow-up should be designed to properly calibrate hormonal supplementation; conversely, niPTMC may sometimes exhibit aggressive behavior, and so the FU regimen should be closer and aimed at early detection of cancer recurrence.

Assessment of Individual and Mixed Effects of Six Minerals on Thyroid Hormones in Chinese Pregnant Women.

The biosynthesis of thyroid hormones is essential for brain and neurological development. It requires iodine as a key component but is also influenced by other nutrients. Evidence for the combined nutrient status in relation to thyroid hormones during pregnancy is limited. We aimed to investigate the joint associations of iodine, selenium, zinc, calcium, magnesium and iron with maternal thyroid functions in 489 pregnant women from Hangzhou, China. Serum levels of six essential minerals and thyroid function parameters were measured during the first antenatal visit. Linear regression, quantile g-computation and Bayesian kernel machine regression were used to explore the individual and joint relationships between the six minerals and thyroid hormones. Linear regression analyses revealed that calcium was positively associated with free triiodothyronine (FT3). Zinc was positively associated with free thyroxine (FT4). Iodine was negatively associated with thyroid-stimulating hormone (TSH) and positively associated with FT3 and FT4. The quantile g-computation and BKMR models indicated that the joint nutrient concentration was negatively associated with TSH and positively associated with FT3 and FT4. Among the six minerals, iodine contributed most to thyroid function. The findings suggested that maintaining the appropriate concentration of minerals, either as individuals or a mixture, is important for thyroid health during pregnancy.

Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma.

BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.