Transgenerational epigenetic self-memory of Dio3 dosage is associated with Meg3 methylation and altered growth trajectories and neonatal hormones.

Intergenerational and transgenerational epigenetic effects resulting from conditions in previous generations can contribute to environmental adaptation as well as disease susceptibility. Previous studies in rodent and human models have shown that abnormal developmental exposure to thyroid hormone affects endocrine function and thyroid hormone sensitivity in later generations. Since the imprinted type 3 deiodinase gene (Dio3) regulates sensitivity to thyroid hormones, we hypothesize its epigenetic regulation is altered in descendants of thyroid hormone overexposed individuals. Using DIO3-deficient mice as a model of developmental thyrotoxicosis, we investigated Dio3 total and allelic expression and growth and endocrine phenotypes in descendants. We observed that male and female developmental overexposure to thyroid hormone altered total and allelic Dio3 expression in genetically intact descendants in a tissue-specific manner. This was associated with abnormal growth and neonatal levels of thyroid hormone and leptin. Descendant mice also exhibited molecular abnormalities in the Dlk1-Dio3 imprinted domain, including increased methylation in Meg3 and altered foetal brain expression of other genes of the Dlk1-Dio3 imprinted domain. These molecular abnormalities were also observed in the tissues and germ line of DIO3-deficient ancestors originally overexposed to thyroid hormone in utero. Our results provide a novel paradigm of epigenetic self-memory by which Dio3 gene dosage in a given individual, and its dependent developmental exposure to thyroid hormone, influences its own expression in future generations. This mechanism of epigenetic self-correction of Dio3 expression in each generation may be instrumental in descendants for their adaptive programming of developmental growth and adult endocrine function.

Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities.

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.

Paraplegic Patient with Metastatic Papillary Thyroid Cancer: A Multidisciplinary Approach to Radioactive Iodine Therapy Safety and Efficacy Strategy.

High-activity radioactive iodine (RAI) therapy for metastatic thyroid cancer (TC) requires isolation to minimize radiation exposure to third parties, thus posing challenges for patients needing hands-on care. There are limited data on the approach to high-activity RAI treatment in paraplegic patients. We report a state-of-the-art multidisciplinary approach to the management of bedbound patients, covering necessary radiation safety measures that lead to radiation exposure levels as low as reasonably achievable. Given the limited literature resources on standardized approaches, we provide a practical example of the safe and successful treatment of a woman with BRAFV600E-mutant tall-cell-variant papillary TC and pulmonary metastases, who underwent dabrafenib redifferentiation before RAI therapy. The patient was 69 y old and had become paraplegic because of a motor-vehicle accident. Since caring for a paraplegic patient with neurogenic bowel and bladder dysfunction poses radiation safety challenges, a multidisciplinary team comprising endocrinologists, nuclear medicine physicians, radiation safety specialists, and the nursing department developed a radiation mitigation strategy to ensure patient and staff safety during RAI therapy. The proposed standardized approach includes thorough monitoring of radiation levels in the workplace, providing additional protective equipment for workers who handle radioactive materials or are in direct patient contact, and implementing strict guidelines for safely disposing of radioactive waste such as urine collected in lead-lined containers. This approach requires enhanced training, role preparation, and practice; use of physical therapy equipment to increase the exposure distance; and estimation of the safe exposure time for caregivers based on dosimetry. The effective and safe treatment of metastatic TC in paraplegic patients can be successfully implemented with a comprehensive radiation mitigation strategy and thorough surveying of personnel for contamination.

Lithium and endocrine disruption: A concern for human health?

Lithium is a key medication for the treatment of psychiatric disorders and is also used in various industrial applications (including battery production and recycling). Here, we review published data on the endocrine-disrupting potential of lithium, with a particular focus on the thyroid hormone system. To this end, we used PubMed and Scopus databases to search for, select and review primary research addressing human and animal health endpoints during or after lithium exposure at non-teratogenic doses. Given the key role of thyroid hormones in neurodevelopmental processes, we focused at studies of the neural effects of developmental exposure to lithium in humans and animals. Our results show that lithium meets the World Health Organization's definition of a thyroid hormone system disruptor - particularly when used at therapeutic doses. When combined with knowledge of adverse outcome pathways linking molecular initiating events targeting thyroid function and neurodevelopmental outcomes, the neurodevelopmental data reported in animal experiments prompt us to suggest that lithium influences neurodevelopment. However, we cannot rule out the involvement of additional modes of action (i.e. unrelated to the thyroid hormone system) in the described neural effects. Given the increasing use of lithium salts in new technologies, attention must be paid to this emerging pollutant - particularly with regard to its potential effects at environmental doses on the thyroid hormone system and potential consequences on the developing nervous system.

Prevalence of thyroid nodule and relationship with physiological and psychosocial factors among adults in Zhejiang Province, China: a baseline survey of a cohort study.

BACKGROUND: Thyroid nodules have attracted much attention due to their high incidence and potential for malignant transformation. Compared with the clinical assessment and diagnosis of thyroid nodules, there are relatively few studies on the epidemiological risk factors for thyroid nodules. The aim of this study was to investigate the prevalence of thyroid nodule among adults in Zhejiang province and to explore their relationship with physiological and psychosocial factors. METHODS: The data used in this study were obtained from the baseline survey of the Zhejiang Provincial Cohort Study on Environment and Health. From June 2022 to December 2023, a total of 21,712 participants from five representative cities in Zhejiang were recruited for the baseline survey. Based on the inclusion and exclusion criteria, 15,595 adults were included in the analysis. The data were collected via self-report questionnaires and physical examinations. Multivariate logistic regression analysis was subsequently performed. RESULTS: The detection rate of thyroid nodules was 50.98% among adults in Zhejiang province. Age, gender, education level, BMI, tea and alcohol consumption all had a statistically significant association with thyroid nodules (p < 0.05). After adjusting for sociodemographic factors, results of logistic regression analysis showed that good life satisfaction (OR = 0.854, 95% CI: 0.780-0.934) had a lower risk of thyroid nodules, however, poor life satisfaction (OR = 1.406, 95% CI: 1.014-1.951), social isolation (OR = 1.294, 95% CI: 1.089-1.538) and a family history of thyroid nodules (OR = 1.334, 95% CI: 1.064-1.672) had a greater risk of thyroid nodules. CONCLUSION: The detection rate of thyroid nodules in adults of Zhejiang province was an increasing trend compared with that in previous years. In addition to the sensitive thyroid nodule screening technology, influencing factors mentioned in this study might also represent credible candidates for this increase. As variable influence factors, weight management, good interpersonal relationships and life satisfaction should be the focus of health interventions.

The clinical value of artificial intelligence in assisting junior radiologists in thyroid ultrasound: a multicenter prospective study from real clinical practice.

BACKGROUND: This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. METHODS: In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. RESULTS: According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P < 0.05). Furthermore, AI assistance significantly improved the performance of junior radiologists in the diagnosis of thyroid nodules, and their diagnostic performance was comparable to that of senior radiologists when pathological results were taken as the gold standard (all p > 0.05). CONCLUSIONS: The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

Suppressed thyroid stimulating hormone levels after initiation of a subcutaneous glucagon-like peptide-1 receptor agonist in a post-thyroidectomy patient managed with levothyroxine case report.

OBJECTIVES: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy has demonstrated an increased risk of thyroid C-cell hyperplasia and C-cell tumors in rodents. Due to this risk, a boxed warning for this drug class exists for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. There is a lack of data regarding any possible effect of GLP-1 RA therapy on serum thyroid levels. The objective of this case report is to describe a case of suppressed thyroid stimulating hormone levels after initiation of a subcutaneous semaglutide in a post-total thyroidectomy patient managed with levothyroxine in order to highlight the need for closer monitoring of these patients and further research in this area. CASE SUMMARY: The patient described in the case underwent a total thyroidectomy in 2015 with stable thyroid hormone replacement requirements with levothyroxine for 5 years until the initiation and titration of subcutaneous semaglutide. The reduction in thyroid stimulating hormone (TSH) after starting GLP-1 RA therapy necessitated a 25 percent dose reduction of levothyroxine from her original dose. PRACTICE IMPLICATIONS: This patient experienced suppressed TSH levels following initiation and titration of subcutaneous semaglutide. The etiology of these changes may be related to the direct effects of GLP-1 RA therapy on TSH levels, changes in absorption related to delayed gastric emptying rates, secondary to GLP-1 RA-associated weight loss, or a combination of these proposed mechanisms. It may be prudent to exercise more frequent monitoring of medications that require weight-based dosing and those with a narrow therapeutic index when initiating and titrating GLP-1 RA-based therapies and is an area of potential study.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Timing of the repeat thyroid fine-needle aspiration biopsy: does early repeat biopsy change the rate of nondiagnostic or atypia of undetermined significance cytology result?

PURPOSE: To determine whether early repeat fine needle aspiration biopsy (FNA) has an effect on adequate or atypia of undetermined significance (AUS) cytology rates in thyroid nodules with inadequate or AUS result in the first FNA. METHODS: Nodules of patients who underwent repeat biopsy due to insufficient or AUS cytology between 2019-2022 were included. Data of the patients and ultrasonographic, cytological and histopathological results of the nodules were recorded. Additionally, the time between the two biopsies was noted. The first was called "initial" and the second was called "rebiopsy". Five different paired groups were formed according to the time between two consecutive biopsies; before and after 1 month, 45 days, 2 months, 3 months, and 6 months. The groups were compared in terms of adequate and AUS cytological results. RESULTS: We evaluated 1129 patients with 2187 nodules undergoing FNAB. After excluding nodules with one FNA result and/or missing data, 966 nodules of 628 patients who underwent FNA at least twice were included. Initial cytology was nondiagnostic (ND) in 665 (30.4%) and AUS in 301 (13.8%) nodules. The mean age of the patients was 52.0 ± 11.9 years, and the female sex ratio was 78.8% (n = 495). There were no differences in adequate or AUS rebiopsy results according to the different time interval groups (p > 0.05 for all). AUS result was statistically insignificantly more frequent in nodules with initially AUS nodules when rebiopsy was performed before 1 month in comparison to after 1 month (53.8%, 27.1%; p = 0.054). Accuracy of rebiopsy was also similar in the time intervals groups (p > 0.05 for all). CONCLUSION: In patients with inadequate or AUS initial biopsy, the rate of adequate or AUS cytology results at rebiopsy did not vary with the timing of repeat biopsy indicating that there may be no need to wait 1 month for a repeat biopsy. In patients with suspicious nodules, biopsy might be repeated before 1 month.

A large, locally aggressive giant cell tumour arising from the laryngeal cartilage: A Rare Case Report.

Giant cell tumour is a growth predominantly found in long bones of the body. Giant cell tumour has a rare occurrence in the head and neck. A case of a 31 year old male with no known comorbidities at the ENT Department, Shifa International Hospital, Islamabad presented with anterior neck swelling and hoarseness of voice. Patient was diagnosed as having Giant Cell Tumour of Larynx (GTCL) proven on FNA cytology and post-operative biopsy. GCTL is an uncommon entity with only 45 reported cases in the world.

LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR-214-3p/UCHL1 axis.

lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual-fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR-214-3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR-214-3p/UCHL1 axis.

A segmentation-based algorithm for classification of benign and malignancy Thyroid nodules with multi-feature information.

The aim of this study is to propose a new diagnostic model based on "segmentation + classification" to improve the routine screening of Thyroid nodule ultrasonography by utilizing the key domain knowledge of medical diagnostic tasks. A Multi-scale segmentation network based on a pyramidal pooling structure of multi-parallel void spaces is proposed. First, in the segmentation network, the exact information of the underlying feature space is obtained by an Attention Gate. Second, the inflated convolutional part of Atrous Spatial Pyramid Pooling (ASPP) is cascaded for multiple downsampling. Finally, a three-branch classification network combined with expert knowledge is designed, drawing on doctors' clinical diagnosis experience, to extract features from the original image of the nodule, the regional image of the nodule, and the edge image of the nodule, respectively, and to improve the classification accuracy of the model by utilizing the Coordinate attention (CA) mechanism and cross-level feature fusion. The Multi-scale segmentation network achieves 94.27%, 93.90% and 88.85% of mean precision (mPA), Dice value (Dice) and mean joint intersection (MIoU), respectively, and the accuracy, specificity and sensitivity of the classification network reaches 86.07%, 81.34% and 90.19%, respectively. Comparison tests show that this method outperforms the U-Net, AGU-Net and DeepLab V3+ classical models as well as the nnU-Net, Swin UNetr and MedFormer models that have emerged in recent years. This algorithm, as an auxiliary diagnostic tool, can help physicians more accurately assess the benign or malignant nature of Thyroid nodules. It can provide objective quantitative indicators, reduce the bias of subjective judgment, and improve the consistency and accuracy of diagnosis. Codes and models are available at https://github.com/enheliang/Thyroid-Segmentation-Network.git.

An overview of the contemporary diagnosis and management approaches for anaplastic thyroid carcinoma.

Thyroid carcinoma is a complex disease with several types, the most common being well-differentiated and undifferentiated. The latter, "undifferentiated carcinoma", also known as anaplastic thyroid carcinoma (ATC), is a highly aggressive malignant tumor accounting for less than 0.2% of all thyroid carcinomas and carries a poor prognosis with a median survival of 5 months. BRAF gene mutations are the most common molecular factor associated with this type of thyroid carcinoma. Recent advances in targeted biological agents, immunotherapy, stem cell therapy, nanotechnology, the dabrafenib/trametinib combination therapy, immune checkpoint inhibitors (ICI) and artificial intelligence offer novel treatment options. The combination therapy of dabrafenib and trametinib is the current standard treatment for patients with BRAF-V600E gene mutations. Besides, the dabrafenib/trametinib combination therapy, ICI, used alone or in combination with targeted therapies have raised some hopes for improving the prognosis of this deadly disease. Younger age, earlier tumor stage and radiotherapy are all prognostic factors for improved outcomes. Ultimately, therapeutic regimens should be tailored to the individual patient based on surveillance and epidemiological data, and a multidisciplinary approach is essential.

Current status of anaplastic thyroid carcinoma.

In this editorial we comment on the article by Pavlidis et al, published in the recent issue of the World Journal of Oncology. We focus on the recent contributions in the management of anaplastic thyroid carcinoma, highlighting the importance of surgery and radiotherapy as first line therapies in its management and the introduction of new systemic therapies beyond chemotherapy, focused on molecular alterations, an essential step in the diagnosis and included in clinical guidelines for the selection of the ideal treatment. In contrast to other neoplasms, immunotherapy, is still beginning in studies of this pathology with encouraging results. Therefore, multimodal management of the pathology together with new drugs seems to be the logical step to increase the survival of this neoplasm.

Toxic Thyroid Adenoma Presenting as Apathetic Hyperthyroidism: A Case Report.

The thyroid gland is an essential endocrine organ that secretes hormones to regulate homeostasis across multiple organ systems throughout the body. It is actively regulated by the hypothalamic-pituitary-thyroid (HPT) axis, where negative feedback modulates the amounts of active hormone being released; thus, lesions that disrupt the proper functioning of this gland or its regulatory mechanisms can be destructive. Toxic thyroid adenomas are usually singular benign functioning nodules in the thyroid gland that cause thyrotoxicosis. Hyperthyroidism is commonly clinically silent, however, in most symptomatic cases, patients will be diagnosed based on abnormal laboratory findings and typical hyperthyroid symptoms. This case report examines an 81-year-old male with an extensive medical history who presented with complaints of new-onset generalized fatigue coupled with bilateral lower extremity muscle cramps. A positron emission tomography (PET) scan for other medical conditions incidentally noted mildly increased uptake in the thyroid gland, prompting a further investigation that resulted in a diagnosis of toxic thyroid adenoma. The patient responded well to treatment with methimazole and has remained in a euthyroid state.

The Heinous Hobnail: A Case Report of the Rare Hobnail Variant of Papillary Thyroid Carcinoma.

The hobnail variant of papillary thyroid carcinoma (HVPTC) represents a distinctive and relatively rare histological subtype of thyroid malignancies. This variant is characterized by its unique cellular morphology with a hobnail appearance, that is, cells with apically positioned nuclei. There are other characteristics like micropapillary pattern and loss of cohesiveness of cells, which are indicative of HVPTC. It can be difficult to distinguish this pattern from other thyroid neoplasms; thus, a thorough microscopical examination is required. Thyroglobulin, thyroid transcription factor-1 (TTF-1), and other thyroid markers are commonly expressed by the tumor cells. Clinically, HVPTC is similar to conventional papillary thyroid cancer (PTC) in many aspects like incidence and epidemiology, but the former is associated with a worse prognosis. According to some research, the hobnail variety might behave more aggressively than conventional PTC, which highlights how crucial it is to identify and comprehend this distinct subtype. While the genetic and molecular underpinnings of HVPTC are still being elucidated, some studies have reported associations with specific genetic alterations, including BRAF, TP53, and TERT mutations. Investigating these molecular signatures may contribute to a better understanding of the variant's pathogenesis and potentially guide targeted therapeutic approaches in the future. In order to customize treatment plans, histopathology is essential in correctly diagnosing it. In this article, we present a case of PTC which presented as a solitary nodule on ultrasonogram in a 40-year-old female.

Papillary Thyroid Carcinoma Concealed Within a Branchial Cyst Without Primary Thyroid Involvement: Unveiling the Enigma.

Branchial cleft cysts are congenital anomalies that form during fetal development and originate from the second branchial cleft. They typically manifest as painless masses on the side of the neck and can become symptomatic when infected. These cysts can create a cavity that may foster infection and, in rare instances, facilitate the spread of primary tumors. It is unusual to find ectopic thyroid tissue within a brachial cyst and it is even rarer to see papillary thyroid carcinoma developing from this tissue. Whenever physicians find a case of lateral neck cyst containing thyroid neoplasm without a known primary in the thyroid, there is always a confusion about whether it is a case of metastatic disease with an undetected primary tumor, or is a carcinoma originating from ectopic thyroid tissue. This is a case report of a papillary thyroid cancer that was unintentionally discovered inside a branchial cyst. So far, only five cases akin to this have been documented. There was no sign of an underlying primary thyroid tumor after the patient had a complete thyroidectomy and selected neck dissection, according to a comprehensive evaluation. This article touches on the development of thyroid tissue within branchial cysts and discusses the etiology of lateral neck tumors. The outcome for such patients appears to be favorable after cyst excision and total thyroidectomy. This article also emphasizes the importance of doing routine histopathological examinations on surgically removed samples that look benign.

Long-term response to MEK inhibitor monotherapy in a patient with papillary thyroid carcinoma harboring BRAF V600E mutation.

Solid tumors harboring mutations in the Braf gene (BRAF) are currently treated by combination Braf/MEK inhibitor therapy, and there is an extensive literature on patient response rates. Alternatively, few studies have documented the clinical response of BRAF mutation-positive solid tumors to MEK inhibitor monotherapy. We report the case of a 57-year-old female diagnosed with papillary thyroid carcinoma and progressive lung metastases initially treated by total thyroidectomy and subsequent thyroid-stimulating hormone suppression therapy. Next-generation sequencing revealed that the tumor harbored a BRAF V600E mutation, and the patient was enrolled in a clinical study of the oral MEK1/2 inhibitor binimetinib. Shortly after starting treatment, the patient experienced pneumothorax due to rapid regression of lung metastases, and computed tomography after 6 months of binimetinib treatment revealed a partial sustained response. One year later, the dose was reduced because of an acneiform rash. After 5 years of binimetinib treatment, lung metastases had regrown, and treatment was switched to the oral multikinase inhibitor lenvatinib. This case demonstrates the potential of MEK inhibitor monotherapy as an alternative treatment for BRAF mutation-positive papillary thyroid carcinoma.

Association between vitamin D status and thyroid cancer: a meta-analysis.

Background: Cumulative evidence has suggested that vitamin D deficiency is related with an increased susceptibility to various types of cancers. However, the association between vitamin D and thyroid cancer (TC) has remained to be unknown. Thus, there has been an urgent need for a meta-analysis to summarize existing evidence on vitamin D levels and the risk of TC. Objective: This meta-analysis aimed to figure out the association between vitamin D level and the risk of TC. Methods: A systematic search was performed for eligible articles on the association between vitamin D and TC based on PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov. Outcomes were the vitamin D level of cases with TC and the incidence of vitamin D deficiency in cases with TC comparing with the controls. The effect measures included standardized mean difference (SMD), ratio of means (RoM), and odds ratio (OR). A dose-response meta-analysis was performed to assess the correlation between vitamin D level and the risk of TC. Subgroup analyses and meta-regressions were conducted to explore the source of heterogeneity. And publication bias was evaluated through Begg's and Egger's tests. Results: Results of the meta-analysis revealed lower levels of vitamin D in TC cases comparing with those in control [SMD = -0.25, 95% CI: (-0.38, -0.12); RoM = 0.87, 95% CI: (0.81, 0.94)] and the levels of 1,25 (OH)D in cases with TC were also lower than controls [SMD = -0.49, 95% CI: (-0.80, -0.19); RoM = 0.90, 95% CI: (0.85, 0.96)]. And vitamin D deficiency was associated with the increased risk of TC [OR = 1.49, 95% CI: (1.23, 1.80)]. Additionally, results from the dose-response meta-analysis showed that there is a 6% increase in the risk of TC for each 10 ng/ml decrease in 25 (OH)D levels [OR = 0.94; 95% CI: (0.89, 0.99)]. Conclusions: Individuals with TC had lower levels of vitamin D compared to controls, and vitamin D deficiency was correlated with an increase risk of TC. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=504417, identifier: CRD42024504417.

The impact of environmental factors and contaminants on thyroid function and disease from fetal to adult life: current evidence and future directions.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research.