Endocrine Tumors Research Articles

Cost-effectiveness of genetic testing of endocrine tumor patients using a comprehensive hereditary cancer gene panel.

Heterogenous clinical manifestations, overlapping phenotypes and complex genetic backgrounds are common in patients with endocrine tumors. There are no comprehensive recommendations for genetic testing and counselling of these patients compared to other hereditary cancer syndromes. The application of multigene panel testing is common in clinical genetic laboratories, but their performance for patients with endocrine tumors has not been assessed. As a national reference center, we prospectively tested the diagnostic utility and cost-efficiency of a multigene panel covering 113 genes representing genetic susceptibility for solid tumors. 1279 patients (including 96 cases with endocrine tumors) were evaluated between October 2021 and December 2022 who were suspected to have hereditary tumor syndromes. The analytical performance of the hereditary cancer panel was suitable for diagnostic testing. Clinical diagnosis was confirmed in 24% (23/96); incidental findings in genes not associated with the patient's phenotype were identified in 5% (5/96). A further 7% of pathogenic/likely pathogenic variants were detected in genes with potential genetic susceptibility roles but currently no clear clinical consequence. Cost-benefit analysis showed that the application of a more comprehensive gene panel in a diagnostic laboratory yielded a shorter turnaround time and provided additional genetic results with the same cost and workload. Using comprehensive multigene panel results in faster turnaround time and cost-efficiently identifies genetic alterations in hereditary endocrine tumor syndromes. Incidentally identified variants in patients with poor prognoses may serve as a potential therapeutic target in tumors where therapeutic possibilities are limited.

Tumor metabolism in pheochromocytomas: clinical and therapeutic implications

Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability. This comprehensive review aims to delineate the multifaceted aspects of tumor metabolism in PPGLs, encapsulating genetic factors, oncometabolites, and potential therapeutic avenues, thereby providing a cohesive understanding of metabolic disturbances and their ramifications in tumorigenesis and disease progression. Initial investigations into PPGLs metabolomics unveiled a stark correlation between specific genetic mutations, notably in the succinate dehydrogenase complex (SDHx) genes, and the accumulation of oncometabolites, establishing a pivotal role in epigenetic alterations and hypoxia-inducible pathways. By scrutinizing voluminous metabolic studies and exploiting technologies, novel insights into the metabolic and genetic aspects of PPGLs are perpetually being gathered elucidating complex interactions and molecular machinations. Additionally, the exploration of therapeutic strategies targeting metabolic abnormalities has burgeoned harboring potential for innovative and efficacious treatment modalities. This review encapsulates the profound metabolic complexities of PPGLs, aiming to foster an enriched understanding and pave the way for future investigations and therapeutic innovations in managing these metabolically unique tumors.

Prognostic factors of adrenocortical carcinoma in children and adolescents: a population-based study.

Adrenocortical carcinoma (ACC) is an uncommon adrenal gland endocrine tumor that has a poor prognosis in children. We aimed toconducta population-based cohort study to predict overall survival (OS) in pediatric patients with ACC. We used the Surveillance, Epidemiology, and End Results (SEER) database to conduct a retrospective cohort research on pediatric patients diagnosed with ACC between 1975 and 2018.We examined demographic characteristics, tumor stage and size, treatment options, and survival results. Kaplane-Meier estimations were used to generate survival curves based on several parameters. To compare survival curves, the log-rank test was applied.Cox proportional-hazards regression was used to determine the variables related with OS. In addition, we created a nomogram to predict overall survival in pediatric ACC patients. A total of 143 pediatric ACC patients were identified. Females were the most impacted (60.8%). Overall 1year, 3year, and 5year survival rates were 75.0%, 57.6%, and 53.7% for all patients, respectively. In comparison to older patients (5-19years), younger patients (≤ 4years) were shown to have more positive characteristics, including a higher likelihood of local disease (29.4% vs. 14%, P < 0.001), tumors less than 10cm (23.1% vs. 14.7%, P < 0.001), and improved overall survival (5year OS 89.6% vs. 27.7%, P < 0.001). Age at diagnosis, SEER stage, and surgery were significant independent predictors of OS in this model, according to the results of Cox proportional hazard regression. After that, we developed a nomogram for predicting OS in children with ACC. Patients older than 4years old had a higher chance of dying. Furthermore, the higher the SEER stage, the higher the risk of death. Patients who do not have surgery have a worse survival rate than those who do. Our study revealed that age at diagnosis, SEER stage, and surgery were found to be the most important predictors of the overall survival of pediatric ACC. These findings contribute to the existing body of knowledge and emphasize the importance of continued research to advance our understanding of pediatric ACC and improve patient care.

Abstract LB050: BRAF V600E is associated with the upregulation of CLDN1 in thyroid cancer

Abstract Thyroid carcinoma is the most prevalent endocrine neoplasm. The most recurrent mutation in thyroid cancer (TC) is the V600E substitution in BRAF, which induces the over-activation of the MAPK pathway. The interaction between this pathway and the deregulation of genes that facilitate tumorigenesis such as CLDN1 could be useful for decision-making related to surgical removal and the degree of initial resection; however, there is a lack of information on the association of CLDN1 expression with BRAF V600E. Objective. Evaluate the gene expression of CLDN1 in BRAF-mutated and BRAF-unmutated thyroid nodules. Methods. RT-qPCR was performed to assess BRAF genotyping (rs113488022) and CLDN1 expression in 94 thyroid nodule biopsy samples (TC=48). Clinicopathological data was retrieved to establish further associations. Results. Mutated BRAF thyroid nodules were found to be 7.14 ± 0.293 times more expressed than those without the mutation (p &amp;lt 0.001, N=94). BRAF V600E mutation was identified in patients with TC exclusively. CLDN1 expression was 41.315 ± 0.554 times greater in patients with TC than in those without TC (p &amp;lt 0.001). Heterozygous patients had a change factor of 6.8, whereas mutated homozygotes had a change factor of 7.5 (p &amp;lt 0.001, N=94). CLDN1 mean expression is significantly higher in A allele carriers compared to normal homozygotes (p &amp;lt 0.001). When analyzing just within the TC group, the behavior is maintained, suggesting a potential association between the mutated allele and the expression of these genes. Conclusion. CLDN1 is significantly upregulated in TC patients carrying the BRAF V600E mutation. BRAF V600E is only observed in patients with TC, implying a biological connection between them, which can be explained via MAPK; subsequent studies are needed to confirm the correlations. Citation Format: Andrea Ross Orozco, Eliakym Arámbula Meraz, Anette Roxana Gastelum Quiroz, Fred Luque Ortega, Edith Eunice García Alvarez, Marco Álvarez Arrazola, Karla Lizbeth Morales Hernández, Noemí García Magallanes. BRAF V600E is associated with the upregulation of CLDN1 in thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB050.

Multidimensional data analysis revealed thyroiditis-associated TCF19 SNP rs2073724 as a highly ranked protective variant in thyroid cancer.

Thyroid cancer represents the most prevalent malignant endocrine tumour, with rising incidence worldwide and high mortality rates among patients exhibiting dedifferentiation and metastasis. Effective biomarkers and therapeutic interventions are warranted in aggressive thyroid malignancies. The transcription factor 19 (TCF19) gene has been implicated in conferring a malignant phenotype in cancers. However, its contribution to thyroid neoplasms remains unclear. In this study, we performed genome-wide and phenome-wide association studies to identify a potential causal relationship between TCF19 and thyroid cancer. Our analyses revealed significant associations between TCF19 and various autoimmune diseases and human cancers, including cervical cancer and autoimmune thyroiditis, with a particularly robust signal for the deleterious missense variation rs2073724 that is associated with thyroid function, hypothyroidism, and autoimmunity. Furthermore, functional assays and transcriptional profiling in thyroid cancer cells demonstrated that TCF19 regulates important biological processes, especially inflammatory and immune responses. We demonstrated that TCF19 could promote the progression of thyroid cancer in vitro and in vivo and the C>T variant of rs2073724 disrupted TCF19 protein binding to target gene promoters and their expression, thus reversing the effect of TCF19 protein. Taken together, these findings implicate TCF19 as a promising therapeutic target in aggressive thyroid malignancies and designate rs2073724 as a causal biomarker warranting further investigation in thyroid cancer.

LINC00891 promotes tumorigenesis and metastasis of thyroid cancer by regulating SMAD2/3 via EZH2.

Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays. To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion apoptosis, and of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting. Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown. In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

How to standardize the diagnostic approach to pituitary neuroendocrine tumors.

Pituitary tumors present heterogeneous biochemical, clinico-radiological, and histological features. Although histologically benign, a non-negligible number of cases present an unpredictable aggressive behavior with local invasiveness, partial/complete resistance to treatment and/or recurrence after surgery, and, rarely, metastasize, overall leading to a significant increase of morbidity, and, thus, requiring skilled multidisciplinary management in referral Centers. Histopathological diagnosis is essential to stratify cancer patient risk and uniform follow-up among Centers. Classification of pituitary neoplasia is continuously evolving in relation to the increased knowledge of mechanisms underlying adenohypophyseal cell tumorigenesis, and the attempts of combining clinico-radiological, biochemical, intraoperative, histological, and molecular elements, with the aim of identifying aggressive forms through. An integrated standardized histopathological report has been proposed in 2019 by the European Pituitary Pathology Group, based on the indications of the 2017 WHO classification of pituitary tumors. The last edition of the WHO Classification of Central Nervous System Tumors and of Endocrine and Neuroendocrine Tumors brought substantial novelties: 1) the replacement of the term "adenoma" with "Pituitary Neuroendocrine Tumor" (PitNET), and of "carcinoma" with "metastatic PitNET," and the consequent ICD-11 recoding from benign to malignant disease; and 2) the pivotal role of lineage restricted pituitary transcription factors for histological typing and subtyping. However, this approach does not reflect the spectrum of tumor phenotypes based on hormone secretion, nor include molecular features. Efforts of interdisciplinary groups of pituitary experts should be strongly encouraged to better understand factors involved in PitNETs evolution and, consequently, standardize diagnosis and reporting based on the most recent knowledges, essential to stratify cancer patient risk and uniform follow-up among centers.

A rare case of extra adrenal retroperitoneal paraganglioma: case report

Extra adrenal retroperitoneal paragangliomas are neuro endocrine neoplasms with extremely rare incidence and a wide plethora of clinical presentations. They originate from the neural crest cells interspersed throughout the body. They can present with vague symptoms of pain abdomen, hypertension, palpitations and in severe cases with renal failure, and shock owing to catecholamine excess. On the other end of the spectrum they can be totally asymptomatic and detected incidentally. The multitude of clinical presentations and lack of specific diagnostic tests hence pose a great difficulty in the pre-operative diagnosis of the disease. We are presenting a case of a 20-year-old female with vague symptoms to highlight the management and clinical diagnosis of extra adrenal retroperitoneal paraganglioma.  

Elevated chorionic gonadotropic hormone in transgenic mice induces parthenogenetic activation and ovarian teratomas

Both male and female reproductive functions are impacted by altered gonadotrophin secretion and action, which may also influence the development of endocrine tumours. To ascertain if chronic hypersecretion of human chorionic gonadotropin (hCG) contributes to the development of gonadal tumours, double transgenic (TG) mice that overexpress hCGα- and β-subunits were analysed. By the age of two months, ovarian tumours with characteristics of teratomas developed with 100% penetrance. Teratomas were also seen in wild-type ovaries orthotopically transplanted into TG mice, demonstrating an endocrine/paracrine mechanism for the hCG-induced ovarian tumorigenesis. Both in vitro and in vivo experiments showed oocyte parthenogenetic activation in TG females. In addition, ovaries showed reduced ovulatory gene expression, inhibited ERK1/2 phosphorylation, and impaired cumulus cell expansion. Hence, persistently high endocrine hCG activity causes parthenogenetic activation and development of ovarian teratomas, along with altered follicle development and impaired ERK1/2 signalling, offering a novel mechanism associated with the molecular pathogenesis of ovarian teratomas.

Clinical, Histopathological, and Radiological Profile of Patients Presenting With Thyroid Malignancies Among the Kerala Population.

Thyroid cancer, though relatively uncommon among all cancer types, stands as the primary form of endocrine tumor. Over the last 20 years, there has been a significant uptick in its occurrence. Papillary thyroid carcinoma (PTC), which is well-differentiated, emerges as the dominant subtype,in regions where iodine levels are deemed adequate. The study aimed to study the clinicopathological profile of patients diagnosed with thyroid malignancies at the Muslim Educational Society (MES) Medical CollegePerinthalmanna. This is a retrospective study undertaken at the MES Medical College by the Department of General Surgery and Endocrine Surgery. The study focuses on patients who have been diagnosed with thyroid cancer through a biopsy. Case sheets of all those patients diagnosed with thyroid malignancy were referred from the Medical Records Library to collect the relevant medical and sociodemographic data. This data was entered in the proforma, which was transferred to the Excel sheet and processed inIBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States). The study included predominantly middle-aged individuals (40-60 years), with 22 (55%) falling within this age range, followed by 14 (35%) aged between 20 and 40 years, and only four (10%) above 60 years. Female patients constituted 82.5% of the study group. Most cases presented with swelling lasting less than six months 23 (57.5%), while only four (10%) had swelling lasting more than five years. Compression symptoms were rare, with only three (7.5%) experiencing dysphagia or dyspnea. Pain was reported in two (5%) of the cases. Hypothyroidism, toxic manifestations, or hoarseness were observed in one (2.5%) of the patients. Regarding swelling characteristics, most were greater than 4 cm in size (29, 72%) and firm in consistency (25, 62.5%). Nodular surfaces were present in 19 (47.5%) of the cases, while 38 (95%) of the swellings were mobile. Palpable lymph nodes were noted in 13 (32.5%) of cases. Radiologically, hypoechoic lesions were observed in 26 (65%) of cases, with microcalcification in 29 (72.5%) and peripheral vascularity in 31 (77.5%). Papillary carcinoma was the most common histological type (34, 85%), with medullary and follicular carcinomas accounting for five (12.5%) and one (2.5%), respectively. An association was found between the duration of swelling and histological type (p = 0.05) and between the mobility of swelling and histological type (p < 0.05). However, no significant associations were observed between imaging findings and histological type (p > 0.05). The gender distribution did not show a statistically significant association with histological type. The findings of the study revealed a statistically insignificant association between age, gender, clinical features, and the histological type of thyroid malignancy. Additionally, there was no statistically significant association between the histological type of thyroid malignancy and the size or type of surface or consistency of thyroid swelling or ultrasonographic findings of the swelling like echogenicity, microcalcification, increased peripheral vascularity, or loss of peripheral halo.

Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification.

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as The Cancer Genome Atlas (TCGA) have revealed the importance of understanding the molecular genetics of thyroid tumors. Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on the cell of origin of tumors and their clinical risk. This paper outlines the following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDNs) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The framework for benign lesions has been revised. The WHO 5th introduces a new category: "developmental abnormalities". Benign FDNs comprise "thyroid follicular nodular disease", follicular thyroid adenoma (FTA), FTA with papillary architecture, and oncocytic adenoma (OA). "Hürthle cell adenoma/carcinoma" is renamed oncocytic adenoma/carcinoma of the thyroid (OA/OCA), which can be distinguished from FTA/FTC by its unique genetic background. 3. Low-risk tumors include NIFTP, TT-UMP, and HTT, and they have an extremely low malignant potential or an uncertain malignant potential. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to their shared genetic and prognostic features. 7. Other miscellaneous tumors are categorized as salivary-gland-type carcinomas of the thyroid, thyroid tumors of uncertain histogenesis, thymic tumors within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies.

State of the Art in 3D Culture Models Applied to Thyroid Cancer.

Thyroid cancer (TC) is the prevalent endocrine tumor with a rising incidence, particularly in higher-income countries, leading to an increased interest in its management and treatment. While overall, survival rates for TC are usually favorable, advanced cases, especially with metastasis and specific histotypes, pose challenges with poorer outcomes, advocating the need of systemic treatments. Targeted therapies have shown efficacy in both preclinical models and clinical trials but face issues of resistance, since they usually induce partial and transient response. These resistance phenomena are currently only partially addressed by traditional preclinical models. This review explores the limitations of traditional preclinical models and emphasizes the potential of three-dimensional (3D) models, such as transwell assays, spheroids, organoids, and organ-on-chip technology in providing a more comprehensive understanding of TC pathogenesis and treatment responses. We reviewed their use in the TC field, highlighting how they can produce new interesting insights. Finally, the advent of organ-on-chip technology is currently revolutionizing preclinical research, offering dynamic, multi-cellular systems that replicate the complexity of human organs and cancer-host interactions.

Synchronous Papillary Thyroid Cancer and Asymptomatic Cervical Lymph Node Sarcoidosis: A Case Report.

Sarcoidosis is a systemic inflammatory disease characterized by the formation of immune granulomas in multiple organs. The cause of this disease is not yet clear. Papillary thyroid cancer (PTC) is the most common malignant endocrine tumor and is often associated with cervical lymph node metastasis. Assessment of risk factors associated with a poor prognosis is crucial in PTC. The coexistence of sarcoidosis and thyroid cancer is rarely reported in the literature. We describe a case of a 54-year-old female diagnosed with PTC and asymptomatic cervical and thoracic hilar lymphadenopathy due to concurrent sarcoidosis. This case will remind clinicians to be aware of the multiple potential causes of lymphadenopathy and realize the importance of the differences in the features of neck lymphadenopathy in patients with suspected head and neck cancer. Overall, careful workup and pretreatment screening enabled us to provide the patient with the most suitable treatment modality and avoid total thyroidectomy.

Investigating the Association of Polygenic Risk Scores With Thyroid Cancer Susceptibility in a Han Chinese Population.

Thyroid cancer, the leading endocrine tumor with a rising global incidence, especially in women, is influenced by both genetic and environmental factors. This study examines the relationship between polygenic risk scores (PRS) and thyroid cancer susceptibility in the Han Chinese population, as well as the impact of genetic variants on clinical outcomes. Analyzing data from 57 257 participants in the Taiwan Precision Medicine Initiative, the study employed the Affymetrix Genome-Wide TWB 2.0 SNP Array for genotyping. PRS were calculated using single nucleotide polymorphisms (SNPs) from prior genome-wide association studies, specifically PGS000087 and PGS000797, and correlated with clinical parameters like age, sex, comorbidities, and treatment methods. Among 4063 participants with thyroid tumors (839 malignant, 3224 benign), higher PRS quartiles correlated significantly with increased thyroid cancer incidence. The highest quartile showed a 1.15-fold (PGS000797) and 1.14-fold (PGS000087) greater risk than the lowest quartile. Key findings included an association between higher PRS quartiles and younger onset age, along with a notable link to chronic kidney disease and thyroid hormone levels in specific SNPs. The study demonstrates PRS's utility in predicting thyroid cancer risk in the Han Chinese population, with higher PRS associated with increased risk and distinct clinical features. While this study focuses on the Han Chinese population, we recognize the importance of comparing PRS performance across different ancestries to fully understand ethnic genetic diversity in cancer risk assessment. Future studies should aim to include such comparative analysis.

Different Ectopic Endocrine Tumors on Renal Hilum Detected by 68Ga-DOTATATE PET.

Renal hilum is a very rare location for primary adrenocortical adenoma or pheochromocytoma. We report 68Ga-DOTATATE PET/CT findings of primary renal hilar adrenocortical adenoma in one patient and 68Ga-DOTATATE PET/MR findings of pheochromocytoma in another patient.

A Rare Case of Co-occurrence of Multiple Endocrine Neoplasia Syndrome and Congenital Adrenal Hyperplasia

Multiple endocrine neoplasia type 1 (MEN1) and congenital adrenal hyperplasia (CAH) are rare monogenic hereditary endocrinopathies with a prevalence of 1–9 cases per 100,000 and 9–15 cases per 100,000, respectively. MEN1 is characterized by the development of multiple endocrine and nonendocrine organ tumors, including parathyroid, pituitary, and duodenopancreatic neuroendocrine tumors (NETs), which constitute the classical triad of the disease. CAH is associated with genetic defects in enzymes and transport proteins involved in the synthesis of adrenal cortical steroid hormones. Overall, cases of the combination of two hereditary diseases in one patient are extremely rare. In this article, we describe a clinical case of the combination of MEN-1 with all three classical components and CAH, which, taking into account the low prevalence of both diseases, represents scientific interest. To date, only one similar case has been described in the literature. In addition, the paper discusses the pathogenetically determined combination of CAH and Ehlers-Danlos syndrome, known as the CAH-X syndrome.

Serum sodium level fluctuations following the resection of childhood-onset craniopharyngioma.

Craniopharyngiomas are low-grade malignancies (WHO I) in the sellar region. Most cases of childhood-onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. This retrospective study measured the serum sodium levels of 202 patients aged 0-18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. The mean age of the cohort was 8.35±4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+ >150mmol/L and serum Na+ <130mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6±7.6mmol/L) and 14 (143.2±6.7mmol/L) and reached their lowest on day 6 (135.5±7.5mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach.

Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment.

Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

Recurrent facial palsy: A CARE case report

IntroductionMiddle-ear adenoma is a rare benign endocrine tumor with slow progression, and can, in very rare cases, lead to recurrent peripheral facial palsy. Case reportA young man experienced three episodes of right peripheral facial palsy of incremental intensity, suggestive of barotrauma. CT and MRI found a tissue mass in the tympanic cavity, and biopsy diagnosed middle-ear adenoma. Electroneuromyography found 50% impairment of facial function. Closed right tympanoplasty with complete tumor resection enabled complete recovery of facial function within 1 month. DiscussionMiddle-ear adenoma is diagnosed on histology, as imaging on MRI can be non-specific, mimicking chronic otitis. Facial involvement is rare and is due to edematous compression of the vasa nervorum. Treatment is surgical, and follow-up should be prolonged. Palsy assessment on electroneuromyography indicates the urgency of treatment.

Quantitative parameters of contrast-enhanced ultrasound effectively promote the prediction of cervical lymph node metastasis in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC), the most common endocrine tumor, often spreads to cervical lymph nodes metastasis (CLNM). Preoperative diagnosis of CLNM is important when selecting surgical strategies. Therefore, we aimed to explore the effectiveness of quantitative parameters of contrast-enhanced ultrasound (CEUS) in predicting CLNM in PTC. We retrospectively analyzed 193 patients with PTC undergoing conventional ultrasound (CUS) and CEUS. The CUS features and quantitative parameters of CEUS were evaluated according to PTC size ≤ 10 or > 10 mm, using pathology as the gold standard. For the PTC ≤ 10 mm, microcalcification and multifocality were significantly different between the CLNM (+) and CLNM (-) groups (both P < 0.05). For the PTC > 10 mm, statistical significance was noted between the two groups with respect to the margin, capsule contact, and multifocality (all P < 0.05). For PTC ≤ 10 mm, there was no significant difference between the CLNM (+) and CLNM (-) groups in all quantitative parameters of CEUS (all P > 0.05). However, for PTC > 10 mm, the peak intensity (PI), mean transit time, and slope were significantly associated with CLNM (all P < 0.05). Multivariate analysis showed that PI > 5.8 dB was an independent risk factor for predicting CLNM in patients with PTC > 10 mm (P < 0.05). The area under the curve of PI combined with CUS (0.831) was significantly higher than that of CUS (0.707) or PI (0.703) alone in the receiver operator characteristic curve analysis (P < 0.05). In conclusion, PI has significance in predicting CLNM for PTC > 10 mm; however, it is not helpful for PTC ≤ 10 mm.