Treatment Of Pituitary Adenomas Research Articles

Pathogenesis, clinical features, and treatment of plurihormonal pituitary adenoma.

Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As yet, its pathogenesis remains unclear. This is the first study to systematically summarize the underlying pathogenesis of PPA. The pathogenesis is related to plurihormonal primordial stem cells, co-transcription factors, hormone co-expression, differential gene expression, and cell transdifferentiation. We conducted a literature review of PPA and analyzed its clinical characteristics. We found that the average age of patients with PPA was approximately 40 years, and most showed only one clinical symptom. The most common manifestation was acromegaly. Currently, PPA is treated with surgical resection. However, recent studies suggest that immunotherapy may be a potentially effective treatment.

The current state of MRI-based radiomics in pituitary adenoma: promising but challenging.

In the clinical diagnosis and treatment of pituitary adenomas, MRI plays a crucial role. However, traditional manual interpretations are plagued by inter-observer variability and limitations in recognizing details. Radiomics, based on MRI, facilitates quantitative analysis by extracting high-throughput data from images. This approach elucidates correlations between imaging features and pituitary tumor characteristics, thereby establishing imaging biomarkers. Recent studies have demonstrated the extensive application of radiomics in differential diagnosis, subtype identification, consistency evaluation, invasiveness assessment, and treatment response in pituitary adenomas. This review succinctly presents the general workflow of radiomics, reviews pertinent literature with a summary table, and provides a comparative analysis with traditional methods. We further elucidate the connections between radiological features and biological findings in the field of pituitary adenoma. While promising, the clinical application of radiomics still has a considerable distance to traverse, considering the issues with reproducibility of imaging features and the significant heterogeneity in pituitary adenoma patients.

MiR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK.

MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization. Transfection of the miR-200b-3p inhibitor and small interfering-RECK (si-RECK) was verified by qPCR. GH3 cell viability and proliferation were detected using CCK8 and EdU assays. Apoptosis was detected by flow cytometry and western blotting. Wound healing and Transwell assays were used to detect cell migration and invasion. The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments. miR-200b-3p was highly expressed in pituitary tumor tissue. Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis, inhibited invasion and migration, and inhibited the expression of matrix metalloproteinases. Interestingly, miR-200b-3p negatively regulated RECK. The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues. Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors, and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression. In summary, this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK. The findings provide a new target for the treatment of pituitary adenoma.

Outcomes and complications of the surgical treatment of pituitary adenomas with cavernous sinus invasion

Outcomes and complications of the surgical treatment of pituitary adenomas with cavernous sinus invasion

From Genes to Therapy: Pituitary Adenomas in the Era of Precision Medicine.

This review presents a comprehensive analysis of pituitary adenomas, a type of brain tumor with diverse behaviors and complexities. We cover various treatment approaches, including surgery, radiotherapy, chemotherapy, and their integration with newer treatments. Key to the discussion is the role of biomarkers in oncology for risk assessment, diagnosis, prognosis, and the monitoring of pituitary adenomas. We highlight advances in genomic, epigenomic, and transcriptomic analyses and their contributions to understanding the pathogenesis and molecular pathology of these tumors. Special attention is given to the molecular mechanisms, including the impact of epigenetic factors like histone modifications, DNA methylation, and transcriptomic changes on different subtypes of pituitary adenomas. The importance of the tumor immune microenvironment in tumor behavior and treatment response is thoroughly analyzed. We highlight potential breakthroughs and innovations for a more effective management and treatment of pituitary adenomas, while shedding light on the ongoing need for research and development in this field to translate scientific knowledge into clinical advancements, aiming to improve patient outcomes.

Enhanced EPR effects by tumour stromal cell mimicking nanoplatform on invasive pituitary adenoma

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.

Unification of pathomorphological examination of patients with neuroendocrine tumors of the pituitary gland. Controversial issues of the new classification

The progressive improvement of the classification using modern analytical methods is an essential tool for the development of precise and personalized approaches to the treatment of pituitary adenomas. In recent years, endocrinologists have witnessed evolutionary changes that have occurred in the histopathological identification of pituitary neoplasms, revealing new possibilities for studying tumorigenesis and predicting biological behavior.The paper considers the historical aspects of the gradual improvement of the classification of pituitary adenomas, as well as the new international 2022 WHO classification, according to which pituitary adenomas are included in the list of neuroendocrine tumors (PitNETs) to reflect the biological aggressiveness of some non-metastatic pituitary adenomas. The characteristics of pituitary adenoma are presented, as well as a list of histological subtypes of aggressive neuroendocrine tumors of the pituitary gland, marked by the main potentials for invasive growth, an increased risk of recurrence and a negative clinical prognosis.The expediency of changing the definition of «pituitary adenoma» to «neuroendocrine tumor» is discussed. It is emphasized that the introduction of a unified clinical, laboratory and morphological protocol into national clinical practice will help provide comparable comparative studies on the prognosis of the disease and the effectiveness of secondary therapy and also contribute to adequate management of potentially aggressive PitNETs.

SAT627 Is Cyberknife Stereotactic Radiosurgery Effective For Treating Cushing’s Disease?

Abstract Disclosure: G. Wintermyer: None. E. Villanueva: None. Patients with pituitary adenoma can often present with endocrine abnormalities. Transsphenoidal surgery(TSS) is the “gold standard” treatment. In patients with recurrent or post-surgery remaining adenoma, stereotactic radiosurgery with CyberKnife (CKRS) has demonstrated to be a good adjuvant therapy. Occasionally patients develop hypopituitarism and adrenal insufficiency (AI) post CKRS. Here is a patient with ACTH-secreting pituitary adenoma with Cushing’s disease who developed remission afterCKRS:52-year-old-male with PMHx of T2DM, hypothyroidism, HTN presented to hospital complaining of fatigue, ataxia, 40-lbs weight loss over four months and mood changes. Due to ataxia, CT of the head was done which revealed an Empty Sella. During the workup, ACTH and cortisol were detected 131 pg/mL and 37.5 ug/dL respectively. After ruling out life-threatening medical conditions, he was discharged with endocrinology referral for Empty Sella syndrome (ESS) and elevated ACTH. During endocrinology evaluation, patient was sent for testosterone, LH, FSH, ACTH, AM cortisol, prolactin and DHEAS tests. Results were as follows: elevated ACTH (91 pg/mL) and Cortisol (33.5ug/dL), elevated DHEAS (401 ug/dL) and prolactin (15 NG/dL), low testosterone (72 NG/dL), within appropriately low LH and FSH. Later, PM Salivary cortisol level, Dexamethasone suppression test(DST), and urine free cortisol (UFC) level were tested. He had pituitary MRI concurrently. Salivary cortisol and UFC were high. There was no suppression of cortisol level after DST. Pituitary MRI demonstrated pituitary tumor. He was diagnosed with Cushing’s disease and was referred to neurosurgery for pituitary tumor TSS. Patient was started on Ketoconazole prior to surgery. Pathology confirmed ACTH-secreting pituitary adenoma. After surgery, Cortisol level normalized, and the patient regained his energy. Post-surgery MRI showed complete resection of adenoma. Ketoconazole was discontinued post-operatively. Two years later, during routine workup, there were elevations in 24-hour and PM salivary cortisol levels. The patient was asymptomatic. He failed his DST. Repeat pituitary MRI showed small hypo enhancement at the bottom of Sella suspicious for pituitary adenoma recurrence. The patient underwent CKRS. Cortisol level and pituitary axis activity remained normal since CKRS. No change was noted in the six-month and one-year surveillance MRI. Even though TSS is a “gold standard” treatment for pituitary adenoma, the likelihood of remaining residues or recurrence of the tumor is high. Frequent pituitary hormone checks can detect recurrence of adenoma before emerging symptoms. CKRS should be considered as a therapeutic option for recurrent adenoma. Clinicians should frequently check patients for hypopituitarism and AI post-CKRS. Clinicians should also recognize that ESS may contribute to MRI-negative Cushing’s disease. Presentation: Saturday, June 17, 2023

FRI555 A Misdiagnosis Of TSH-secreting Adenoma With Thyrotoxicosis In A Patient With Graves’ Disease

Abstract Disclosure: J. Huynh: None. A. Makawi: None. G. Elshimy: None. Introduction: Modern healthcare relies on laboratory and imaging results for accurate diagnosis and medical decision-making. However, the collection and distillation of laboratory results is a multi-step process with the potential for error at each stage. This may result in diagnostic errors. A review of salient cases is one avenue to improving awareness of the risk for failure in the laboratory assessment process. We present one such case of a patient initially referred to neurosurgery for management of a thyroid stimulating hormone (TSH) secreting microadenoma, which is a rare disease and accounts for less than 1% of all pituitary adenomas, with incongruent laboratory presentation including elevation in TSH and free T4. Endocrinology consultation prompted further investigations which led to the diagnosis of Graves’ disease with a concomitant nonfunctional pituitary microadenoma. Case Presentation: This is a case of a 61-year-old white male who presented with 30-lb weight loss, insomnia, palpitations, and diaphoresis. Initial thyroid stimulating hormone (TSH) from outside facility was > 90 mcIU/mL with elevated free T4 of 23.4 pg/mL. MRI of the brain shows a 3x3 mm pituitary microadenoma raising concern for an atypical case of TSH-secreting adenoma. The patient referred to Neurosurgery for evaluation by primary care. Endocrinology was consulted for evaluation prior to any surgical intervention. A large goiter was noted on exam. Clinical presentation was highly concern for Graves’ disease. Repeated labs included undetectable TSH with FT4 of 4.4 pg/mL and free T3 12.9 pg/ml. TPO-ab was elevated at 17.1 IU/mL. TSIg index was low. Ultrasound of the thyroid gland revealed a normal thyroid without nodules. He was diagnosed with Graves’ disease and was initiated on methimazole and propranolol with symptomatic improvement. His pituitary panels continued to show suppressed TSH pre and post treatment with no other significant pituitary abnormalities hence the diagnosis of a concomitant nonfunctional pituitary microadenoma was made. Discussion: Ultimately, the initial TSH-secreting microadenoma has deemed a misdiagnosis and he was subsequently treated appropriately for Graves’ disease with normalization of thyroid functions. Standard of care for any laboratory abnormalities is to assess for reproducibility of the result. In our patient, subsequent in-house and outside assays were unable to demonstrate elevation of both TSH and FT4. Instead, the patient had suppressed TSH with elevated FT4, without evidence of nodules consistent with Graves’ disease. Treatment of Graves’ disease differs greatly from the treatment of TSH-secreting pituitary adenoma, which includes surgical resection, radiotherapy, and/or, a somatostatin analog based on the clinical picture. Correct diagnosis prevented our patients from unnecessary surgical complications and lifelong morbidity. Presentation: Friday, June 16, 2023

Research progress on the role of the Wnt signaling pathway in pituitary adenoma.

Pituitary adenoma (PA) is the third most common central nervous system tumor originating from the anterior pituitary, but its pathogenesis remains unclear. The Wnt signaling pathway is a conserved pathway involved in cell proliferation, Self-renewal of stem cells, and cell differentiation. It is related to the occurrence of various tumors, including PA. This article reviews the latest developments in Wnt pathway inhibitors and pathway-targeted drugs. It discusses the possibility of combining Wnt pathway inhibitors with immunotherapy to provide a theoretical basis for the combined treatment of PA.

Management and risk of postoperative bleeding in patients with low-dose antiplatelet aspirin medication during endoscopic endonasal surgery for pituitary adenomas.

To analyze the risk of postoperative bleeding following endoscopic endonasal transsphenoidal surgery (EETS) for treatment of pituitary adenomas (PA) in patients with short-term discontinuation of low-dose aspirin, if required for prevention of artherothrombotic disease (ATD). Patients with preoperative aspirin medication were identified in this single-center retrospective analysis of consecutive patients with PA, who underwent EETS between December 2008 and June 2022. Aspirin was discontinued perioperatively less than 2days, > 2 and < 4days, and > 4 and < 7days according to the assumed risk of perioperative ATD. For those patients, the rate of postoperative bleeding, which required surgery, was compared to patients without aspirin. Forty-five (14.8%) out of 304 patients underwent EETS with short-term perioperative aspirin discontinuation. Thirty-six (80%) patients discontinued aspirin < 2days, 6 (13.3%) patients > 2 and < 4days, and 3 patients (6.7%) > 4 but < 7days. Postoperative bleeding rate was not increased in patients with short-term perioperative aspirin discontinuation. One patient (0.3%) without perioperative aspirin medication underwent revision surgery for treatment of postoperative hemorrhage with suprasellar extension. Eight patients (2.6%) had postoperative epistaxis (1 patient (0.3%) with short-term discontinuation and 7 patients (2.3%) without aspirin). Patients with perioperative aspirin were significantly older (68.3 ± 8.6 vs. 57.9 ± 14.1; p < 0.01) and had a significantly lower rate of hormonally active tumors (11.1% vs. 25.1%; p < 0.05) compared to patients without aspirin. No differences were found for tumor characteristics (tumor extension, tumor volume, largest diameter) between both groups. Short-term discontinuation of low-dose aspirin was not associated with increased rate of postoperative bleeding in patients, who underwent EETS for treatment of PA.

Surgical Strategies in the Treatment of Giant Pituitary Adenomas.

The management of giant pituitary adenomas (GPAs) is challenging due to associated endocrinopathies and the close proximity of these tumors to critical structures, such as the optic nerves, structures of the cavernous sinus, and hypothalamus. The objective of this review article was to summarize the current management strategies for giant pituitary adenomas, including the role of open and endoscopic surgical approaches and the role of medical and radiation therapy in conjunction with surgery. We conducted a retrospective review of GPAs operated at our institute between January 2010 and March 2023. Surgical approaches, extent of resection, and associated complications were documented. Furthermore, we conducted a thorough literature review to identify relevant studies published in the past decade, which were incorporated along with insights gained from our institutional case series of GPAs to analyze and integrate both the existing knowledge base and our institution's firsthand experience in the management of GPAs. A total of 46 giant pituitary adenomas (GPAs) were operated on, using various surgical approaches. Transsphenoidal approach was used in 25 cases and a staged approach using transsphenoidal and pterional was used in 15 cases. Other approaches included transcortical-transventricular, transcallosal, pterional/orbitozygomatic, and subfrontal approaches. Complications and technical nuances were reported. The management of giant pituitary adenomas remains complex, often involving several modalities-open or endoscopic resection, radiosurgery, and medical management of both the tumor and associated endocrinopathies. Surgical resections are often challenging procedures that require careful consideration of several factors, including patient characteristics, tumor location, and size, and the experience and skill of the surgical team.

Mini review of the pathogenesis, incidence, and treatment of Pituitary adenomas

In this review article, we are discussing the origin of pituitary tumors. We are showing the pathological transcription factors playing role in the differentiation of the pituitary cells. We are also describing the regulation of pituitary hormone secretion, describing the incidence of pituitary tumors, and at length describe the modern treatment of them with surgery, medications, or stereotactic radiosurgery (gamma knife) as well as a combination of different treatment modalities.

Pituitary adenoma or neuroendocrine tumour: the need for an integrated prognostic classification.

In the 2022 fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, pituitary adenomas are reclassified as neuroendocrine tumours (NETs). This change confers an oncology label to neoplasms that are overwhelmingly benign. A comprehensive clinical classification schema is required to guide prognosis, therapy and outcomes for all patients with pituitary adenomas. Pituitary adenomas and NETs exhibit some morphological and ultrastructural similarities. However, unlike NETs, pituitary adenomas are highly prevalent, yet indolent and rarely become malignant. This Perspective presents the outcomes of an interdisciplinary international workshop that addressed the merit and clinical implications of the classification change of pituitary adenoma to NET. Many non-histological factors provide mechanistic insight and influence the prognosis and treatment of pituitary adenoma. We recommend the development of a comprehensive classification that integrates clinical, genetic, biochemical, radiological, pathological and molecular information for all anterior pituitary neoplasms.

A Preoperative Nomogram for Prediction of Postoperative Hypocortisolism in Patients with Pituitary Adenomas: A Single-Center Retrospective Cohort Study

Patients with pituitary adenomas (PAs) are at an increased risk preoperatively and postoperatively for hypopituitarism. Postoperative hypocortisolism is associated with increased mortality and morbidity as well as poor quality of life. However, research about the risk factors for postoperative hypocortisolism is limited, and a predictive nomogram for postoperative hypocortisolism has not yet been developed. We aimed to investigate the predictive factors for postoperative hypocortisolism and construct a dynamic online nomogram. Our database included 438 consecutive PA patients who were hospitalized and treated with transsphenoidal surgery by experienced neurosurgeons from the different medical teams in the Neurosurgery Department, Jinling Hospital, between January 2018 and October 2020. The final study group included 238 eligible patients. Data on possible predictors, including age, sex, treatment history of PAs, preoperative signs and symptoms, primary recurrence subtype, and clinical subtypes, were collected. Univariable and multivariable logistic regression analyses were applied to identify independent predictors, which were included in constructing the nomogram model. The calibration curve and receiver operating characteristic curve were computed to evaluate the predictive performance of the nomogram model. The incidence of postoperative hypocortisolism was 12.08%. Three preoperative predictors were identified to construct the nomogram: surgical type (microscopic or endoscopic, with endoscopic surgery proven to be the protective factor) (odds ratio, 0.24; 95% confidence interval [CI], 0.093-0.610; P= 0.003), prothrombin time (odds ratio, 2.40; 95% CI, 1.332-4.326; P= 0.004), and basophil cell count (odds ratio, 5.25; 95% CI, 1.270-21.816; P= 0.022,). The area under the curve of receiver operating characteristic curve for the constructed nomogram was 0.749 (95% CI, 0.640-0.763); a well-fixed calibration curve was generated for the nomogram model. An interactive web-based dynamic nomogram application was also constructed. In this study, surgical type, prothrombin time, and basophil cell count were the most relevant predictive factors for postoperative hypocortisolism. A predictive nomogram that can preoperatively assess the risk of hypocortisolism after surgical treatment of PAs was developed. This nomogram could be helpful in identifying high-risk patients who require close monitoring of serum cortisol levels and initiating clinical procedures for patients requiring cortisol administration therapy as a lifesaving strategy.

Postsurgical outcomes of nonfunctioning pituitary adenomas: a patient-level meta-analysis.

Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis. An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan-Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed. Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27-0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15-0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08-0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92-1.30, p = 0.301). This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis. PROSPERO CRD42022374034.

Acromegaly in the differential diagnosis of hearing loss

Acromegaly is a multifactorial neuroendocrine disease caused by hyperproduction of growth hormone (GH). In more than 95% of cases the reason of acromegaly the GH-secreting pituitary adenoma. In patients with this neuroendocrine disease, a slowly developing complex of symptom can manifest with concomitant pathological conditions, including auditory function disordersDiagnostic difficulties of acromegaly at the ambulatory stage determine the importance of doctor`s awareness in different medical specialties.Here we demonstrate a clinical case of the improvement of the auditory function due to combined surgical and medical treatment of a patient with the pituitary macroadenoma, acromegaly and hearing loss.Anamnesis features: a patient with an active stage of acromegaly and a pituitary macroadenoma measuring 57x35x32 mm with ante-, supra-, infra-, parasellar spread, (Knosp III(D), Knosp IV(S) noted a violation of auditory function. She was consulted by an otolaryngologist, sensorineural hearing loss on the right of the 3rd degree was diagnosed, on the left of the 1st degree. The patient underwent surgical treatment of pituitary adenoma, noted a significant improvement in auditory function in the early postoperative period. Six months later, repeated audiometry was performed, marked regression of hearing damage was noted.The case described by us indicates the reversibility of a rare complication of acromegaly - hearing loss and the importance of an interdisciplinary approach in the management of patients with this pathology.

Analysis of the Prognostic and Immunological Role of HSPB1 in Pituitary Adenoma: A Potential Target for Therapy.

Background and Objectives: The diagnosis and treatment of pituitary adenomas with cavernous sinus invasion pose significant challenges for clinicians. The objective of this study is to investigate the expression profile and prognostic value of HSPB1 (heat shock protein beta-1) in pituitary adenomas with invasive and non-invasive features. Additionally, we aim to explore the potential relationship between HSPB1 expression and immunological functions in pituitary adenoma. Materials and Methods: A total of 159 pituitary adenoma specimens (73 invasive tumours and 86 non-invasive tumours) underwent whole-transcriptome sequencing. Differentially expressed genes and pathways in invasive and non-invasive tumours were analysed. HSPB1 was subjected to adequate bioinformatics analysis using various databases such as TIMER, Xiantao and TISIDB. We investigated the correlation between HSPB1 expression and immune infiltration in cancers and predicted the target drug of HSPB1 using the TISIDB database. Results: HSPB1 expression was upregulated in invasive pituitary adenomas and affected immune cell infiltration. HSPB1 was significantly highly expressed in most tumours compared to normal tissues. High expression of HSPB1 was significantly associated with poorer overall survival. HSPB1 was involved in the regulation of the immune system in most cancers. The drugs DB11638, DB06094 and DB12695 could act as inhibitors of HSPB1. Conclusions: HSPB1 may serve as an important marker for invasive pituitary adenomas and promote tumour progression by modulating the immune system. Inhibitors of HSPB1 expression are currently available, making it a potential target for therapy in invasive pituitary adenoma.

Pasireotide LAR Treatment for Non-functioning Pituitary Adenoma: A Case Report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Machine learning driven prediction of cerebrospinal fluid rhinorrhoea following endonasal skull base surgery: A multicentre prospective observational study.

Cerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis. A dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score. CSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches. Neural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling.