Prospective Study on Coblation Vs. Cautery in Endoscopic Trans Sphenoidal Surgery for Pituitary Macroadenoma: Impact on Nasal Function.

Endoscopic endonasal Trans-sphenoidal surgery for sellar-suprasellar tumors is considered the preferred route. The ideal instruments in skull base surgery should be able to manipulate adequately through the narrow corridors with effective tissue removal and bleeding control and reduce collateral damage to nearby vital structures. The present study sought to compare the nasal morbidity following transnasal sphenoidal surgery for pituitary macroadenoma using Coblation and Electrocautery. 160 undergoing Endoscopic TSS for non-functioning PAs were enrolled. The patients were randomly allocated into Coblation (n = 80) and electrocautery (n = 80) groups. All operations were performed by the same group of surgeons skilled in their surgical techniques. There were 59 and 53 patients with Knosp grade II tumors in the cautery and coblation group, respectively, while 21 and 27 patients had Knosp grade III tumors. The average duration of surgery using cautery was 96+/-4.5 min, while with coblation, the average time was 83+/-3.5 min, and the difference was statistically significant. Nasal crusting and granulation severity were observed more in the electrocautery group. The coblation group patients had clear surgical fields with few ooze points; the difference between the two groups was significant. Nasal synechiae and decreased nasal patency were common in the electrocautery group. There were no statistical differences in nasal bleeding, nasal deformity, or sense of smell parameters. Advanced medical tools like coblation are safe and effective for the dissection and ablation of the mucosa. They result in better intra-operative visualization and lesser postoperative nasal morbidity, which will help patients achieve a better quality of life.

Characterizing pituitary adenomas in clinical notes: Corpus construction and its application in LLMs.

Objective: Faced with the challenges of differential diagnosis caused by the complex clinical manifestations and high pathological heterogeneity of pituitary adenomas, this study aims to construct a high-quality annotated corpus to characterize pituitary adenomas in clinical notes containing rich diagnosis and treatment information. Methods: A dataset from a pituitary adenomas neurosurgery treatment center of a tertiary first-class hospital in China was retrospectively collected. A semi-automatic corpus construction framework was designed. A total of 2000 documents containing 9430 sentences and 524,232 words were annotated, and the text corpus of pituitary adenomas (TCPA) was constructed and analyzed. Its potential application in large language models (LLMs) was explored through fine-tuning and prompting experiments. Results: TCPA had 4782 medical entities and 28,998 tokens, achieving good quality with the inter-annotator agreement value of 0.862-0.986. The LLMs experiments showed that TCPA can be used to automatically identify clinical information from free texts, and introducing instances with clinical characteristics can effectively reduce the need for training data, thereby reducing labor costs. Conclusion: This study characterized pituitary adenomas in clinical notes, and the proposed method were able to serve as references for relevant research in medical natural language scenarios with highly specialized language structure and terminology.

Comprehensive transcriptomic analysis identifies three distinct subtypes of pituitary adenomas: insights into tumor behavior, prognosis, and stem cell characteristics.

BACKGROUND: Pituitary adenomas (PAs) are the second most common intracranial tumor. While current diagnostic practices rely primarily on histological testing, they often fail to capture the molecular complexities of pituitary adenomas, underscoring the need for a molecular-based classification to refine therapeutic strategies and prognostic assessments. This study aims to provide a molecularly unbiased classification of pituitary adenomas and explore their unique gene expression patterns and clinical features. METHODS: We performed unsupervised hierarchical clustering of the gene expression profiles of 117 PA samples to identify three distinct molecular subtypes. Subsequently, we analyzed the compiled transcriptomic profiles of each individual subtype for pathway enrichment. We also validated the new classification with a validation set containing 158 PAs and 24 pituitary adenoma stem cells (PASCs). RESULTS: Consensus clustering of transcriptomic data from 117 pituitary adenoma (PA) samples identified three distinct molecular subtypes, each showing unique gene expression patterns and associated biological processes: Group I is enriched in signaling pathways, such as the cAMP signaling pathway and the calcium signaling pathway. Group II is primarily related to metabolic processes, including nitrogen metabolism and arginine biosynthesis in cancer. Group III predominantly shows enrichment in immune responses and potential malignant transformation of the disease, especially through cancer-related pathways such as the JAK-STAT signaling pathway and the PI3K-Akt signaling pathway. The immune profiling revealed distinct patterns for each subtype: Group I had higher dendritic cells and fewer CD8+ T cells, Group II had more monocytes and macrophages, and Group III had elevated levels of T cells. Additionally, there were differences in clinical characteristics and prognosis among the subtypes, with Group III having a worse prognosis, despite the smaller tumor size compared to other groups. Notably, differences in PASCs correlated with the molecular subtypes, with Group III stem cells being enriched in tumorigenesis pathways, PI3K-Akt signaling pathway and Ras signaling pathway. CONCLUSION: Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification.

Long term outcomes of pituitary adenomas in Multiple Endocrine Neoplasia type 1: a nationwide study.

Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.

Diagnosis and management of pituitary adenomas in children and adolescents.

BACKGROUND: Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. AIMS: We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. CONCLUSIONS: Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Invasive pituitary adenoma presenting with cerebrospinal fluid rhinorrhea and meningitis - A case report.

Background: Most pituitary neuroendocrine tumors are benign, except some adenomas that show invasiveness and are called invasive pituitary adenomas. These are challenging and rare pathologies. Case Description: We present a case of a 40-year-old male who presented to the emergency with seizures, rhinorrhea, headache, and drowsiness. Radiology images showed a sellar mass with supra-sellar extension and pneumocephalus. The pituitary profile was within normal limits. The patient underwent bifrontal craniotomy and maximum safe resection of the lesion with cerebrospinal fluid (CSF) leak repair and lumbar drain insertion. Histological examination and immunohistochemical stain were consistent with pituitary adenoma. Postoperatively, there was no CSF leak, and the patient's Glasgow Coma Scale improved. Conclusion: Rhinorrhea is a unique presentation for pituitary adenoma. According to the current literature, surgery is the only effective treatment as part of the management of invasive pituitary adenomas, along with a multidisciplinary approach.

The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential.

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications.

Expression assays of selected lncRNAs in non-functioning pituitary adenomas.

PURPOSE: Non-functioning pituitary adenomas (NFPAs) are a group of these neoplasms originated from the adenohypophyse and do not show evidence of hormonal oversecretion. However, different genes and lncRNAs have been found to be dysregulated in these samples. MATERIAL AND METHODS: In this study, in order to identify novel biomarkers, a set of regulatory lncRNAs for the two important hub genes, i.e. STAT3 and EGFR were selected and subjected to experimental investigation. These lncRNAs were EGFR-AS1 for the EGFR gene, and LINC00240, FALEC and SNHG12 for the STAT3 gene. RESULTS: All studied genes were down-regulated in NFPA samples compared with normal tissues adjacent to the tumors (NTATs), except for FALEC whose expression was not different between these two sets of samples. EGFR was the most significantly down-regulated gene in NFPAs (Expression ratio (95% CI) = 0.009 (0.002-0.04), P value < 0.0001). ROC curve analyses proposed that the expression levels of SNHG12, EGFR, EGFR-AS1 and LINC00240 can be used to distinguish NFPAs from NTATs with AUC values of 0.88, 0.83, 0.7 and 0.66, respectively. Spearman's correlation analyses showed significant correlations between FALEC and EGFR-AS1 in both types of tissues, and between FALEC and EGFR in NFPAs. Moreover, expression of LINC00240 was correlated with EGFR-AS1, FALEC and SNHG12 in NFPAs. CONCLUSION: Taken together, EGFR and STAT3-related lncRNAs may be involved in the pathogenesis of NFPA.

Phenotypic presentation of MEN1 c.758delC (p.Ser253Cysfs *28) pathogenic variant: a case report.

MEN1 is a rare syndrome caused by mutations in the MEN1 gene. We describe a clinical case of MEN1 syndrome associated with a recently discovered pathogenic mutation of MEN1 gene. A 32-year-old man with a history of osteopenia, nephrolithiasis, hypercalcemia and hypophosphatemia, impaired fasting glucose, and asthenia was admitted to our outpatient unit. Primary hyperparathyroidism, sustained by three hyperplastic parathyroid glands, was diagnosed. Prolactin- and GH-secreting adenomas were ruled out. After undergoing subtotal parathyroidectomy, the patient was diagnosed with non-functioning pituitary adenoma, three pancreatic lesions, and Cushing syndrome sustained by left adrenal adenoma. The patient underwent left adrenal surgery; somatostatin analogue lanreotide was started for the pancreatic lesions; the pituitary adenoma, being small and non-secreting, was not treated. A genetic test was performed to confirm the diagnosis of MEN1 syndrome, finding an association with a recently discovered mutation: the (NM_130799.2):c.758delC (p.Ser253Cysfs*28) in exon 4.

"Intrasellar tumor-to-tumor metastasis: A single center experience with a systematic review".

PURPOSE: This study investigates the rare occurrence of tumor-to-tumor metastasis in Pituitary Neuroendocrine Tumors (PitNETs), also known as pituitary adenomas, aiming to enhance understanding of its diagnostic and therapeutic challenges. We report two cases from our institution of tumor-to-tumor metastasis involving PitNETs, followed by a systematic literature review. METHODS: We conducted a comprehensive literature review using PubMed and Google Scholar databases. This review provides insights into patient demographics, clinical presentations, primary tumor origin, management approaches and outcomes. RESULTS: We identified 38 documented cases of tumor-to-tumor metastasis involving the pituitary gland in the literature. This revealed a diverse range of primary tumor origins, with lung, breast, and renal carcinomas being the most prevalent. Clinical presentations varied, with visual disturbances emerging as the most frequently reported symptom. Surgical interventions predominantly resulted in subtotal resection. Kaplan-Meier survival analysis demonstrated that endoscopic endonasal approaches (EEA) are associated with longer median survival times compared to other surgical methods. CONCLUSION: Tumor-to-tumor metastasis to PitNETs must be considered in differential diagnoses of sellar masses. Prompt and accurate diagnosis, coupled with a multidisciplinary treatment strategy, is essential. Our study contributes to the scarce literature on such metastases, providing a foundation for further understanding of this complex pathological entity.

Exosomal AFAP1-AS1 Promotes the Growth, Metastasis, and Glycolysis of Pituitary Adenoma by Inhibiting HuR Degradation.

Exosomal long noncoding RNAs (lncRNAs), which are highly expressed in tumor-derived exosomes, regulate various cellular behaviors such as cell proliferation, metastasis, and glycolysis by facilitating intercellular communication. Here, we explored the role and regulatory mechanism of tumor-derived exosomal lncRNAs in pituitary adenomas (PA). We isolated exosomes from PA cells, and performed in vitro and in vivo assays to examine their effect on the proliferation, metastasis, and glycolysis of PA cells. In addition, we conducted RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, and ubiquitination assays to investigate the downstream mechanism of exosomal AFAP1-AS1. Exosomes from PA cells augmented the proliferation, mobility, and glycolysis of PA cells. Moreover, AFAP1-AS1 was significantly enriched in these exosomes and stimulated the growth, migration, invasion, and glycolysis of PA cells in vitro, as well as tumor metastasis in vivo. It also enhanced the binding affinity between Hu antigen R (HuR) and SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1), resulting in HuR ubiquitination and degradation accompanied by enhanced expression of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). Moreover, HuR overexpression alleviated the exosomal AFAP1-AS1-mediated promotion of growth, metastasis, and glycolysis effects. These findings indicate that tumor-derived exosomal AFAP1-AS1 modulated SMURF1-mediated HuR ubiquitination and degradation to upregulate HK2 and PKM2 expression, thereby enhancing PA cell growth, metastasis, and glucose metabolism. This suggests targeting exosomal AFAP1-AS1 may be a potential strategy for the treatment of PA.

KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary Study.

Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial-mesenchymal transition (EMT)-an underlying NF-PitNET pathogenic mechanism-were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67+ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14.

The nomogram for predicting nasal bleeding after endoscopic transsphenoidal resection of pituitary adenomas: a retrospective study.

Objective: This study aimed to develop and validate a dynamic nomogram to assess the risk of nasal bleeding after endoscopic transnasal transsphenoidal pituitary tumor resection. Methods: A retrospective analysis was conducted on patients who underwent endoscopic transnasal transsphenoidal pituitary tumor resection from June 2019 to June 2021. Univariate and multivariate logistic regression analyses were used to screen for independent risk factors for nasal bleeding from the training set. A multivariate logistic regression model was established, a nomogram was plotted, and it was validated in an internal validation set. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: The nomogram indicators included anticoagulant use, sphenoid sinus artery injury, nasal irrigation, platelet count (PLT), and constipation. The predictive model had an area under the ROC curve of 0.932 (95% CI: 0.873-0.990) and 0.969 (95% CI: 0.940-0.997) for the training and validation sets, respectively, indicating good discrimination. The calibration curve showed good consistency between the actual and predicted incidence of nasal bleeding (p > 0.05). DCA indicated that the nomogram had good clinical net benefit in predicting postoperative nasal bleeding in patients. Conclusion: In summary, this study explored the incidence and influencing factors of nasal bleeding after endoscopic transnasal transsphenoidal pituitary tumor resection and established a predictive model to assist clinical decision-making.

Approaches based on natural products and miRNAs in pituitary adenomas: unveiling therapeutic intervention.

Pituitary adenomas (PAs) are tumors originating in the pituitary gland, a small gland located at the base of the brain. They are the most common type of pituitary tumor, affecting approximately 1 in 10 people over their lifetime. Common symptoms include headaches, vision problems, hormonal imbalances, and weight changes. Treatment options depend on the type and size of the adenoma and may consist of medication, surgery, radiation therapy, or a combination. PAs are typically benign and slow-growing, but they can cause significant health issues if left untreated. Proper diagnosis and management by an experienced multidisciplinary team is important for achieving the best outcomes. Natural compounds like celastrol, curcumin, quercetin, apigenin, resveratrol, epigallocatechin gallate (EGCG), and genistein have shown the ability to inhibit cell growth, promote cell death, and suppress hormone activity in pituitary tumor cells, suggesting their potential as alternative or complementary treatments for PAs. MicroRNAs (miRNAs) are a kind of tiny RNA molecules that do not code for proteins and have a vital function in controlling gene expression. These 21-23 nucleotide-long molecules regulate gene expression by binding to complementary sequences in mRNA molecules, leading to mRNA degradation. miRNAs participate in a wide range of biological activities, including apoptosis, metastasis, differentiation, and proliferation. The research indicates that miRNAs play a crucial role in the pathogenesis, therapeutic approaches, diagnosis, and prognosis of PAs. This review article will provide a comprehensive analysis of the current understanding of the efficacy of naturally derived anti-cancer agents in the treatment of PAs. Furthermore, the study provides a comprehensive assessment of the miRNAs in PAs, their role in the development of PAs, and their potential application in the treatment of the condition.

Phenotype and genotype of patients with multiple endocrine neoplasia type 1 studied in Argentina / Fenotipo y genotipo de pacientes con neoplasia endocrina múltiple tipo 1 estudiados en Argentina

Abstract Introduction: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gas troenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phe notype and genotype of Argentinian patients with MEN1. Methods: A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation. Results: Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were mis sense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers. Conclusion: The phenotype and genotype of Argen tinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.

Resumen Introducción: La neoplasia endocrina múltiple tipo 1 (NEM1) es una enfermedad hereditaria autosómica dominante con una prevalencia estimada de 2-10:100 000. Las localizaciones principales de los tumores son glándulas paratiroides (HPT), tracto gastroenteropan creático (TGEP) y glándula pituitaria (TP). El objetivo de nuestra investigación fue describir el fenotipo y genotipo de pacientes argentinos con NEM1. Métodos: Estudiamos 68 casos índices diagnostica dos por presentar al menos dos de los tres tumores principales, o un tumor y un pariente con NEM1, y 84 familiares de primer grado. Secuenciamos la región codificante (exones 2-10); el promotor, exón 1; y las re giones intrónicas flanqueantes del gen MEN1 siguiendo el método de Sanger. Utilizamos MLPA en pacientes índice sin mutación. Resultados: Prevalencia de tumores: HPT 87.5%, TGEP 49% (p < 0.001), sin diferencias estadísticas entre las prevalencias de HPT vs TP (68%). Prevalencia de variantes patogénicas: 90% en casos familiares y 51% en esporádi cos. Hallamos 36 variantes patogénicas, 7 (20%) fueron noveles. Fueron 13 (36.2%) microarreglos con cambio en el marco de lectura, 9 (25%) variantes sin sentido, 8 (22.2%) con cambio de sentido, 3 (8.3%) en sitio de unión de empalme, 2 (5.5%) grandes deleciones y 1 microarre glo sin cambio en el marco de lectura. El 39 % (n = 33) de los parientes de primer grado en 23 familias fueron portadores de mutaciones. Conclusión: El fenotipo y genotipo de los pacientes argentinos con NEM1 fue similar al de otras poblaciones. Destacamos una alta frecuencia de TP y de variaciones patogénicas noveles.

The diverging role of O-GlcNAc transferase in corticotroph and somatotroph adenomas.

PURPOSE: Molecular mechanisms involved in the pathogenesis and tumor progression of pituitary adenomas (PA) remain incompletely understood. Corticotroph and somatotroph PA are associated with a high clinical burden, and despite improved surgical outcomes and medical treatment options, they sometimes require multiple surgeries and radiation. Preliminary data suggested a role for O-GlcNAc Transferase (OGT), the enzyme responsible for the O-GlcNAcylation of proteins. O-GlcNAcylation and OGT have been found elevated in other types of tumors. METHODS: We evaluated 60 functioning and nonfunctioning PA (NFPA) from operated patients and postmortem normal and tumoral pituitary tissue by immunohistochemistry. We performed transcriptomic analyses to explore the relevance of the O-GlcNAc Transferase (OGT) in PAs. We detected OGT in immunobiological analysis and define its level in PA tissue in patients. RESULTS: OGT was strongly associated with PA hormone secretory capacity in functioning PA and with tumor growth in NFPAs. In NFPAs, OGT was positively associated with tumor size but not with cavernous sinus invasion (Knosp grading). In GH-secreting PA, OGT expression was negatively correlated with circulating Insulin-like Growth Factor 1 level. In adrenocorticotropic hormone (ACTH)-secreting PA, OGT expression was positively associated with circulating ACTH levels. OGT did not correlate with tumor size in secreting PAs. OGT levels were higher in gonadotroph PA compared to normal glands. CONCLUSION: O-GlcNAcylation can be downregulated in non-cancerous tumors such as GH-secreting adenomas. Future studies are warranted to elucidate the role of OGT in the pathogenesis of PAs.

Does New WHO 2022 Nomenclature of Pituitary Neuroendocrine Tumors Offer an Extra Edge to the Neurosurgeons for Its Management? A Narrative Review.

The new World Health Organization nomenclature of pituitary tumors was introduced in the year 2022 after much deliberation. This nomenclature clearly demarcates the anterior lobe (adenohypophyseal), posterior lobe (neurohypophyseal), and hypothalamic tumors. There is also focus on other tumors arising in the sellar region. The nomenclature has also advocated the routine use of immunohistochemistry in describing the pituitary transcription factors that plays a fundamental role in distinguishing the cell lineage of these tumors. However, the nomenclature is complex in understanding due to inclusion of pathological correlates like transcription factors, hormones, biomarkers, and various controversies that have emerged regarding the renaming of pituitary adenomas (PA) as PiTNETs ("Pituitary Neuroendocrine tumors") because majority of the adenomas are benign and have rare metastatic behavior while classifying them as PiTNETs will create unnecessary misinterpretation of these as aggressive tumors that will lead to apprehension among the patients. The new classification gives deeper insight into the histological picture of the various pituitary tumors but other than contributing to the follow-up strategy and postsurgery management, this classification does not add anything new that could be advantageous for the neurosurgeons in clinical practice and decision making, especially in deciding the plan of action for surgery. Hence, there is need of a more comprehensive, integrated, neuroradiological-based classification with more emphasis on the invasiveness of these tumors that would assist the neurosurgeons in planning the treatment strategy and managing patients of pituitary tumors.

A Non-Secreting Pituitary Adenoma That Changed to a Prolactinoma.

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the "hook effect"), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL.

Advancement in perioperative management of pituitary adenomas-Current concepts and best practices.

Pituitary adenomas are very common representing 18.1% of all brain tumors and are the second most common brain pathology. Transsphenoidal surgery is the mainstay of treatment for all pituitary adenomas except for prolactinomas which are primarily treated medically with dopamine agonists. A thorough endocrine evaluation of pituitary adenoma preoperatively is crucial to identify hormonal compromise caused by the large sellar mass, identifying prolactin-producing tumors and comorbidities associated with Cushing and acromegaly to improve patient care and outcome. Transsphenoidal surgery is relatively safe in the hands of experienced surgeons, but still carries a substantial risk of causing hypopituitarism that required close follow-up in the immediate postoperative period to decrease mortality. A multidisciplinary team approach with endocrinologists, ophthalmologists, and neurosurgeons is the cornerstone in the perioperative management of pituitary adenomas.

Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.