Search

Rhinorrhea is a common complication after endoscopic endonasal transsphenoidal pituitary surgery (EETPS). This study evaluates the effectiveness of our sellar reconstruction technique in preventing rhinorrhea. From June 2020 to March 2024, a surgical team performed 490 EETPS procedures on 458 pituitary adenoma patients. Demographic data, surgery status, and radiological and histopathological classifications were retrospectively analyzed. 4 grades for sellar reconstruction were defined based on intraoperative cerebrospinal fluid (CSF) leakage and diaphragm sella defect size. Grade 0: no CSF leakage; cavity filled with absorbable material. Grade 1: small defect; covered with fat and fascia lata grafts. Grade 2: large defect; added lumbar drainage. Grade 3: extended approach; added nasoseptal flap. Of the 490 operations, 433 were primary and 57 recurrent. Patients were 50.2% male, mean age 49.01 years. Follow-up averaged 20.5 months. Postoperative rhinorrhea occurred in 8 cases (1.6%). In 404 surgeries (82.5%) without intraoperative CSF leakage, 3 cases (0.7%) developed postoperative rhinorrhea. CSF leakage was detected in 86 cases (17.5%), with postoperative rhinorrhea in 5 cases (5.8%). The risk of rhinorrhea was 8.3 times higher with intraoperative CSF leakage (P = 0.005). Rhinorrhea rates: 0.7% in Grade 0, 3% in Grade 1, 8.7% in Grade 2, and 0% in Grade 3 (P = 0.017). Meningitis occurred in 8 patients (1.7%) and pneumocephalus in 4 (0.9%), with one death (0.2%). The average hospital stay was 17.4 days with rhinorrhea and 5.2 without (P = 0.024). Intraoperative CSF leakage is highly correlated with rhinorrhea. Multilayered and graded closure strategies significantly reduce postoperative rhinorrhea rates in EETPS. [ABSTRACT FROM AUTHOR]

Routine evaluation and surveillance imaging after pituitary adenoma (PA) endoscopic endonasal transsphenoidal resection (EETS) is a neurosurgical practice to identify tumor recurrence. This study aims to identify social and clinical factors that may contribute to patients missing their initial 1-year follow-up appointment and provide guidance for targeted education to improve patient adherence with postoperative treatment plans, ultimately reducing unknown adenoma recurrence. The authors performed a single-center retrospective review of patients who underwent EETS for PAs from 2007 to 2023. Patients were analyzed for sociodemographic factors, presenting symptoms, time to surgery, surgical outcomes, and adherence to postoperative follow-up visits at 1 year after surgery. A total of 256 patients with PAs treated by EETS met inclusion criteria; 218 (85%) of these patients attended 1-year follow-up, and 38 (15%) missed this visit. Twenty-nine (76%) individuals who missed their 1-year follow up were men (P = 0.006). Divorced/widowed/separated patients were 2 times more likely to miss their follow-up compared with their married counterparts (P = 0.008). Additional significant risk factors included older age, as the mean age for patients who missed their 1-year appointment was 60.1 years compared with 54.7 years (P = 0.028). Patients with visual field deficits at initial presentation were also less likely to follow-up at 1 year (P = 0.03). Risk factors of missed 1-year follow-up appointments after PA resection include male sex, divorced/widowed/separated marital status, older age, and the presence of visual deficits at initial presentation. Increased education efforts can be selectively aimed at these at-risk patient cohorts to improve patient compliance and reduce consequences of undetected tumor recurrence. [ABSTRACT FROM AUTHOR]

Objective: To provide a review on acromegaly and its orofacial manifestations, with a focus on associated arthropathies and temporomandibular joint disorders (TMD). Methods: A review of current literature was performed through an electronic search of three databases: PubMed, ScienceDirect, and Google Scholar. The literature review was focused on the following topics of interest: etiology, diagnosis, and management of acromegaly, orofacial manifestations of acromegaly, acromegalic arthropathies, and acromegaly‐associated TMD. Results: Acromegaly is a chronic multisystem condition in which excessive production of growth hormone in adults, most commonly caused by benign pituitary adenomas, leads to somatic overgrowth. Orofacial changes are considered hallmarks of the disease. It is important for dentists to recognize signs and symptoms of acromegaly, as this may help to achieve early diagnosis and improve overall disease prognosis. Acromegalic arthropathies typically involve large joints, however, the temporomandibular joints (TMJ) can be affected. TMD associated with acromegaly is under‐recognized and poorly characterized in current literature. Conclusion: In the appropriate clinical context, acromegaly should be considered as part of the differential diagnosis for patients presenting with TMD. Further studies are needed to better characterize the nature of TMD associated with acromegaly and to define the role of TMJ involvement in early diagnosis. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenomas are benign tumors located in the anterior hypophysis. Its appearance is associated with the development of parameters related to metabolic syndrome; therefore, surgical treatment could reduce associated morbimortality. Methods: Pre- and post-surgical MRI, using the Hardy–Wilson and Knosp classification, and clinical data according to the American Association of Clinical Endocrinology (AACE) criteria for metabolic syndrome: all the patients were followed-up until 208.57 days were reviewed on 217 consecutive patients with pituitary surgery. Results: Seventy-four patients were included in this study. There was a significant reduction in tumor size in mm3 [average pre- and post-surgery respectively: 12,362 mm3 (±12,397); 3,910 mm3 (±7,160)], (p < 0.0001). This was confirmed by the Hardy–Wilson and Knosp classification, where most patients went from grade IV C (33.7%) to grade 0 (12.1%), IA (20.2%), IIB (21.36%), and IIC (16.2%); as well as from grade 4 (24.3%) to grade 0 (45.9%), respectively. After surgery, there were statistically significant reductions in total serum levels of glucose [average pre- and post-surgery, respectively: 116 mg/dL (±26.9); 90 mg/dL (±10.2)], (p < 0.001), triglycerides [average pre- and post-surgery, 240 mg/dL (±102); 171 mg/dL (±60.5)], (p = 0.001); and HDL-c [average pre- and post-surgery, respectively: 39 mg/dL (±11.8); 44.6 mg/dL (±8.4)], (p = 0.029). The other parameters remained unchanged. Conclusion: This is the first study to demonstrate the relationship between the presence of pituitary adenoma and significative changes in serum glucose, triglycerides and c-HDL related to metabolic syndrome. [ABSTRACT FROM AUTHOR]

Brain tumor classification is a significant issue in computer aided diagnosis to make a convenient treatment. Deep learning techniques are surpassing traditional brain tumor classification methods in the medical image field with advanced hardware technology. In this article, a novel classification framework has been proposed that includes pre-trained fine-tuned EfficientNet B7. The framework focuses on a multi-class classification problem to distinguish among three common types of brain tumors, i.e., gliomas, meningiomas, and pituitary tumors. The proposed classification framework is trained and tested using six optimization algorithms SGD, RMSProp, Adagrad, Adam, Adadelta, and Nadam using two classifiers softmax and support vector machine (SVM). The best performance achieved by Nesterov-accelerated adaptive moment estimation (Nadam) optimizer using softmax classifier with test accuracy 99 % , average precision 99.3 % , average recall 97.3 % and average F1-score 98 % which outperformed other state-of-the-art architectures on Figshare MRI image data set. The proposed framework has also been evaluated, and performance has been compared using two more publicly available standard four-class brain tumor MRI data sets. [ABSTRACT FROM AUTHOR]

Pituitary adenomas are a type of of the most frequent intracranial tumors. These tumors can extend outside the sella, but very rarely originate ectopically to the sellar region. A 71-year-old patient presented to our institution, with prior clinical history of noncontrolled arterial hypertension and new-onset high-intensity pulsatile headache. Upon suspicion of a hypertensive emergency with probable brain compromise, a nonenhanced computed tomography of the head was performed. A mass within the sphenoid sinus was found. Endocrinological workup demonstrated a significant elevation of the growth hormone. As an incidental finding, a brain aneurysm was evidenced, which was treated endovascularly prior to the mass treatment. Subsequently, the patient successfully underwent a gross total resection through an endonasal transsphenoidal approach. Histopathological results were consistent with a pituitary ectopic adenoma. A postoperative improvement in levels of somatomedin C was documented postoperatively. [ABSTRACT FROM AUTHOR]

Objective: Thyrotropin‐secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single‐centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long‐term remission. Design, Patients and Measurements: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long‐term remission. Results: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space‐occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. Conclusions: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long‐term endocrinological remission. [ABSTRACT FROM AUTHOR]

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology “atypical adenoma” for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD‐O and ICD‐11 codes for PitNET tumor behavior from a neoplasm either “benign” or “unspecified, borderline, or uncertain behavior” to “malignant” neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome. [ABSTRACT FROM AUTHOR]

Context Prolactinoma, the most common subtype of pituitary adenoma, is rare in children and adolescents. Clinical presentation and treatment outcomes of prolactinomas in this population have been evaluated insufficiently. Objective To summarize the clinical features, both medication and surgical outcomes of prolactinomas in children and adolescents in a large retrospective cohort from China. Methods A cohort of patients with prolactinomas aged ≤20 years at diagnosis between 2012 and 2021 in Peking Union Medical College Hospital were retrospectively analyzed. Results The cohort comprised 170 patients (115 females and 55 males, median age 16.6 years), with 20.0% (23/115) girls without menarche and 33.3% (18/54) boys in prepuberty. The median maximal diameter was 15.0 mm (61.2% macroadenomas and 4.6% giant adenomas), and the median baseline prolactin (PRL) level was 211.0 ng/mL. Larger sizes and higher PRL levels were observed in girls without menarche at diagnosis and in boys. Most girls presented with menstrual disturbance (86.7%), and boys were frequently bothered by headaches (42.6%), reduced height velocities (25.9%), and delayed puberty (18.2%). Dopamine agonists (DAs) were used as first-line treatment in 133 patients, and the resistance rate was 22.5% (25/111), independently associated with maximal tumor diameters (P =.035). Surgery was performed in 76 patients. Long-term surgical remission rates were 32.9% (25/76) overall, negatively associated with cavernous sinus invasion independently (P =.025), 59.4% (19/32) in noninvasive tumors (64.0% in 25 noninvasive macroadenomas), and 5.0% (1/20) in invasive tumors. Conclusion Pediatric prolactinomas exhibited more severe clinical characteristics in boys and in patients diagnosed during earlier stages of pubertal developments. Given the overall efficacy of PRL normalization by medication and considerable surgical remission rate in noninvasive tumors, DAs remain the first-line recommendation for prolactinomas in children and adolescents, while surgery might be viable for noninvasive tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET. [ABSTRACT FROM AUTHOR]

Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor‐ and/or treatment‐related damage to the hypothalamus. HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment‐related HO (TTR‐HO) patients. The algorithm is used to estimate incidence rates of TTR‐HO patients in the German healthcare context from a representative claims database (n = 5.42 million) covering 2010–2020. Patients were identified based on surgery/radiotherapy procedures and HO‐associated tumor diagnoses (n = 3976). HO was defined by incident obesity and validated based on incident diabetes insipidus diagnoses and desmopressin prescription within a 12‐month period after surgery/radiotherapy. Uncertainty due to algorithm definitions is explored in sensitivity analyses. Estimated annual incidence of TTR‐HO in Germany is between 0.7 and 1.7 cases per 1,000,000 persons (2019 prevalence: n = 1262 patients). With observed cases in all age groups, two HO‐incidence peaks are identified: children/young adults aged 10–24 years and adults aged 40–44 years. Most frequent HO‐validated tumor diagnoses are benign sellar/suprasellar tumors (6.1/1,000,000 persons over 9 years), including tumors of the craniopharyngeal duct (1.3/1,000,000), neoplasms of the pituitary gland (4.1/1,000,000), and nonspecific brain tumors of endocrine glands (2.4/1,000,000). This is the first real‐world database analysis of TTR‐HO epidemiology, refining current estimates of HO epidemiology and early patient identification. A more comprehensive characterization of patients with HO as well as a better understanding of clinical implications will be crucial in developing optimal treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Skull base tumors, can cause oculomotor dysfunction, presenting a management challenge given their proximity to cranial nerves. This study investigated the oculomotor outcomes in patients with skull base tumors presenting cranial nerve palsy due to tumor compression and aimed to identify associated factors. Methods: This retrospective observational cohort study enrolled patients diagnosed with primary skull base tumors who exhibited cranial nerve palsy due to tumor compression, confirmed by magnetic resonance imaging treated at Asan Medical Center between January 2011 and December 2022. Patients were assessed for oculomotor function pre- and post-treatment, and categorized into recovery and non-recovery groups based on outcomes. Factors associated with oculomotor outcomes were also analyzed. Results: Fifty-six patients were enrolled, with the majority (n = 37, 66.1%) demonstrating recovery in oculomotor function post-treatment. The duration from symptom onset to treatment initiation was short in the recovery group, suggesting that early treatment may contribute to improved oculomotor outcomes. The type of tumor was significantly associated with oculomotor outcomes, with patients with pituitary adenoma exhibiting better outcomes. In the recovery group, 19/37 (51.4%) patients underwent surgical resection alone. In contrast, in the non-recovery group, 17/19 (89.5%) patients received primary or adjuvant radiosurgery or radiation therapy. Conclusion: Approximately 70% of patients with skull base tumors experienced recovery in oculomotor function post-treatment. The duration before treatment and the type of tumor were significantly associated with the oculomotor outcome. These findings aid neuro-ophthalmologists in predicting oculomotor outcomes for patients with skull base tumors, guiding management strategies for oculomotor dysfunction. [ABSTRACT FROM AUTHOR]

Pituitary adenoma/pituitary neuroendocrine tumors (PitNETs) are the second most common primary intracranial tumor and the most frequent neuroendocrine tumors/neoplasms of the human body. Thus, they are one of the most frequent diagnoses in neuropathologist's practise. 2022 5th edition WHO Classification of Endocrine and Neuroendocrine Tumors does not support a grading and/or staging system for PitNETs and argues that histological typing and subtyping are more robust than proliferation rate and invasiveness to stratify tumors. Numerous studies suggest the existence of clinically relevant molecular subgroups encouraging an integrated histo‐molecular approach to the diagnosis of PitNETs to deepen the understanding of their biology and overcome the unresolved problem of grading system. The present review illustrates the main issues involved in establishing a grading and a staging system, as well as alternative systems validated by independent series to date. The state of art of the current histological and molecular markers is detailed, demonstrating that a standardized and reproducible clinico‐pathological approach, combined with the integration of molecular data may help build a workflow to refine the definition of PitNETs with ‘malignant potential’ and most importantly, avoid delay in patient treatment. Next molecular studied are needed to validate an integrated histo‐molecular grading for PitNETs. [ABSTRACT FROM AUTHOR]

The evolution of classification systems of pituitary adenomas (now PitNETs) has culminated in the use of transcription factor (TF) immunohistochemistry (IHC), forming a cell lineage‐based system. However, several issues remain to be addressed, including the additional financial and logistic burden of undertaking the complete array of anterior pituitary hormones and TF IHC. To that end, several groups have suggested algorithms to minimise the number of tests performed, with varying levels of diagnostic accuracy. Although the proportion of null cell tumours has decreased following the use of TFs, “multilineage” tumours have been reported and characterised using transcriptomic signatures, most prominently the PIT1‐SF1 co‐expressing PitNETs, which do not bear a position in the present system of classification. In this review, we examine the proposed practical approaches to the diagnosis of PitNETs. We review the literature on reported PitNET types that challenge the existing classification system, such as those that express multiple TFs, with their potential clinical implications. Finally, we assess limitations in the present system, such as the lack of a standardised system for IHC interpretation, that need to be addressed in the future. [ABSTRACT FROM AUTHOR]

AbstractBackgroundCase reportConclusionPrimary pituitary lymphoma (PPL) is a rare finding in immunocompetent patients, with only 54 patients reported to date (including ours). It presents most often with headache and hypopituitarism, with MRI findings comparable to more common pituitary tumours, making the diagnosis challenging. There is no consensus on the ideal management for these lesions with the role of surgical resection not clearly established.We present here a 49-year-old female who presented with acute vision loss and was found to have PPL of diffuse large B-cell lymphoma, non-germinal centre type. The radiologic findings were distinct from prior cases with haemorrhagic components and perilesional edoema in the bilobed sellar mass. Surgical resection was halted when a diagnosis of lymphoma was suspected. This decision was based on the guidelines for the treatment of primary CNS lymphoma (PCNSL) and the lack of evidence to support surgical resection of PPL specifically. Our patient lacked mutations commonly associated with a poor prognosis in DLBCL, such as TP53 and BCL6. She remains in remission with normal vision nearly two years after treatment with minimal resection, MR-CHOP, and consolidation radiotherapy.We highlight here the clinical and diagnostic features of PPL to guide clinicians to early recognition and diagnosis. Surgical resection should be limited to what is necessary to obtain a diagnosis and critical decompression; otherwise, these lesions respond excellently to steroids and typical chemoradiation regimens. [ABSTRACT FROM AUTHOR]

Background: Although visual field (VF) defects are common in compressive pituitary adenoma (CPA), their pathophysiology has not been fully elucidated. The mechanical theory (i.e., direct compression of the optic chiasm by the CPA) and the vascular theory (i.e., compression of the vessels supplying the visual path by the CPA) or their association could explain the visual impairment. The aim of this study was to determine whether the vascular density (VD) improved after surgical decompression of the optic chiasm in CPA patients and whether OCT-A could help to identify predictive factors for postoperative visual recovery. Methods: A prospective controlled study was conducted in patients who underwent transsphenoidal pituitary adenoma surgery. Patients were divided into two groups: with CPA and without CPA (NCPA). All patients underwent a neuro-ophthalmological examination, VF testing, macular and optic disc structural OCT [retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thicknesses] and OCT-A before and then 1 and 6 months after surgery. Results: Twenty-four eyes and fourteen eyes were included, respectively, in the CPA and NCPA groups. None of the VD parameters assessed by OCT-A were significantly improved after surgery in the CPA group. In the CPA group, the mean macular superficial VD was significantly decreased at 6 months. The multivariate analysis failed to identify any preoperative parameters predictive of postoperative VF improvement. Conclusions: Our preliminary findings suggest that the visual impairment observed in CPA patients could not be explained by the vascular theory. None of the preoperative OCT-A parameters allowed a postoperative VF recovery assessment. Trial registration number NCT04074642, ID-RCB 2019-A01186-51 date of registration 30 July 2019. [ABSTRACT FROM AUTHOR]

Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)‐independent and ACTH‐dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH‐independent hypercortisolemia. ACTH is derived from pro‐opiomelanocortin, and its processing involves prohormone convertase 1/3. High‐molecular‐weight ACTH is generally found in ACTH‐producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high‐molecular‐weight ACTH alternation during ACTH‐independent Cushing's syndrome remain unclear. A 40‐year‐old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH‐independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non‐suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high‐molecular‐weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high‐molecular‐weight ACTH levels was observed. Histological findings revealed cortisol‐producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high‐molecular‐weight ACTH. The observed decline in high‐molecular‐weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic–pituitary–adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH‐related molecules warrants further exploration to enhance our understanding of the hypothalamic–pituitary–adrenal axis feedback mechanism. [ABSTRACT FROM AUTHOR]

This article provides an overview of the 2021 WHO classification of nervous tumors, focusing on gliomas, glioneuronal tumors, and neuronal tumors. It discusses the historical revisions made to the classification and highlights the changes introduced in the latest edition. The article emphasizes the role of advanced technologies, such as methylome analysis, in classifying CNS tumors and mentions the contributions of the cIMPACT-NOW consortium. It also provides a list of references to scientific articles that cover various aspects of brain tumor classification and characterization. This information is valuable for researchers and medical professionals studying and treating brain tumors. [Extracted from the article]

This study investigated differential gene expression between granulation patterns in growth hormone (GH)-secreting pituitary tumors, aiming to elucidate novel transcriptomes that explain clinical variances in patients with acromegaly. Transcriptome analysis was conducted on 6 normal pituitary tissues and 15 GH-secreting pituitary tumors, including 9 densely granulated somatotroph tumors (DGSTs) and 6 sparsely granulated somatotroph tumors (SGSTs). We identified 3111 differentially expressed genes (DEGs) in tumors compared to normal pituitaries, with 1117 DEGs unique to a specific granulation within tumors. SGST showed enrichment of neuronal development and acute inflammatory response pathways, along with a significant enhancement of JAK-STAT, phosphatidylinositol 3-kinase, and MAPK signaling. The results suggest that granulation-specific gene expression may underpin diverse clinical presentations in acromegaly, highlighting the potential for further investigation into these transcriptomic variations and their roles in disease pathology, particularly the involvement of genes linked to neuronal development, inflammatory response, and JAK-STAT signaling in SGST. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center. Methods: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7–297.6) months. Results: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5–141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708–6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032–12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found. Conclusion: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS. [ABSTRACT FROM AUTHOR]

Pituitary neuroendocrine tumors (PitNETs) are common, most likely benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNET types are classified according to their expression of specific transcriptional factors (TFs) and hormone secretion levels. Some types show aggressive, invasive, and reoccurrence behavior. Current research is being conducted to understand the molecular mechanisms regulating these high-heterogeneous neoplasms originating from adenohypophysis, and single-cell RNA sequencing (scRNAseq) technology is now playing an essential role in these studies due to its remarkable resolution at the single-cell level. This review describes recent studies on human PitNETs performed with scRNA-seq technology, highlighting the potential of this approach in revealing these tumor pathologies, behavior, and regulatory mechanisms. [ABSTRACT FROM AUTHOR]

This article presents a case study of a Colombian family with a rare variant of Multiple Endocrine Neoplasia type 1 (MEN1). The study follows the medical history and diagnoses of the affected family members and emphasizes the importance of genetic screening and surveillance in early detection and personalized treatment of MEN1. The study also identifies a frameshift variant in the MEN1 gene that may contribute to the variability in clinical manifestations observed in the family. While the findings provide valuable insights, further research is needed to confirm their significance due to the limited sample size of the study. [Extracted from the article]

Elevated concentrations of T3 and T4 concomitant with nonsuppressed TSH are found in both TSH-producing tumors and resistance to thyroid hormone beta (RTHß), posing a diagnostic challenge. We demonstrate here a 54-year-old female who presented with palpitations, goiter, and elevated free T4 with nonsuppressed TSH concentrations (TSH 2.2 mIU/L [normal range, NR 0.27-4.2 mIU/L] and FT4 59.08 pmol/L [NR 12.0-22.0 pmol/L]). Because magnetic resonance imaging revealed a pituitary microadenoma (4 mm), she was diagnosed with TSH-secreting pituitary adenoma and underwent transsphenoidal surgery. Pathological reports showed no tumor cells. Subsequent genetic testing revealed a pathogenic variant in the THRB gene resulting in a His435Arg amino acid substitution in the T3 receptor isoform beta 1 (TRß1), suggestive of RTHß. In vitro and ex vivo studies revealed that the His435Arg mutated TRß1 (TRß1-H435R) completely abolishes the T3-induced transcriptional activation, nuclear receptor corepressor 1 release, steroid receptor coactivator 1 recruitment, and T3-induced thyroid hormone target gene expression, confirming the pathogenicity of this variant. The identification of a pituitary microadenoma in a patient with RTHß led to a misdiagnosis of a TSH-producing tumor and unnecessary surgery. Genetic testing proved pivotal for an accurate diagnosis, suggesting earlier consideration in similar clinical scenarios. [ABSTRACT FROM AUTHOR]

Somatic alpha thalassemia/mental retardation syndrome X-linked (ATRX) pathogenic variants have been shown to predict a malignant phenotype in neuroendocrine tumors. They were recently identified in aggressive pituitary tumors and carcinomas, mainly of corticotrophic origin. To our knowledge, these tumors are rare in a general cohort of pituitary tumors, with no cases described in null cell tumors. These variants can lead to loss of protein expression as revealed by immunohistochemistry. We describe a case of an aggressive null cell pituitary tumor with loss of ATRX expression. The patient underwent two transsphenoidal surgeries and radiotherapy and exhibited tumor growth despite conventional therapy. Analysis of the tumor samples revealed loss of ATRX expression in both surgical specimens, suggesting that ATRX may be a useful biomarker for the early identification of aggressive pituitary tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

McCune-Albright syndrome (MAS) is a rare genetic, non-inheritable disease and is characterized by fibrous dysplasia, hyperendocrinism, and café-au-lait macules. Pituitary adenomas could be concurrent with this syndrome but clinicopathological features and the surgical management of such disorders is unclear. We retrospectively reviewed ten MAS-associated pituitary adenoma patients with follow-up in Beijing Tiantan Hospital and analyzed their clinicohistological data, surgical strategies, neuro-imaging, genetic mutations, and prognosis. Moreover, a critical review of the English language literature was also conducted. All of the ten MAS-associated adenoma patients underwent surgeries to remove the tumor (nine transsphenoidal approaches and one transcranial approach). None of these patients had a decompression of the optic canal. Notably, the growth hormone (GH), prolactin (PRL), and IGF-1 level had a significant reduction after the resection of the tumor while vision improvement was observed in most patients (6/7) with visual deficits. No tumor recurrence was observed during the follow-up from 16 to 150 months. The pathological examination showed a moderate Ki-67 LI (mean 1.19%, range from 0.1% to 3.3%) and the positive staining of Gsα and PKA C-beta. GNAS gene mutation (R201C) was detected in one patient. Hormone excess (including GH and PRL) could be significantly reduced and the visual deficits are greatly improved after the surgery without the decompression of the optic canal. In addition, MAS-associated pituitary adenomas have a moderate expression of Ki-67 and positive expression of Gsα and PKA C-beta, indicating a mildly proliferative nature of these tumors and the possible linking between MAS and adenomas. [ABSTRACT FROM AUTHOR]

Thyrotroph pituitary adenomas have been reported to be a rare cause of 'thyroid storms', causing myriad metabolic and autonomic disturbances. In this case, we describe the second reported case in literature of a 'GH storm' in an infarcted somatotroph adenoma. We describe a residual invasive somatotroph macroadenoma that underwent infarction, producing a dramatic elevation in serum GH levels. While infarction of adenomas may in some cases lead to remission, the patient went on to require re-surgery and re-radiation due to growth of the residual viable tumour. 'GH storms' are rare but interesting events that may occur in somatotroph adenomas. Infarction or apoplexy must be considered when managing residual adenomas. [ABSTRACT FROM AUTHOR]

Extent of resection is a major determinant of outcomes following pituitary surgery. Intra-operative magnetic resonance imaging (iMRI), provides an immediate assessment of the extent of resection, allowing further tumour resection during the same procedure. However, such systems are expensive and significantly increase operative time, prompting some authors to question the additional benefit conferred by iMRI when combined with endoscopy. Our aim was to assess the impact of combining 3 T iMRI with endoscopy in patients with pituitary tumours. We retrospectively reviewed a prospectively maintained database to identify patients who underwent iMRI guided endoscopic resection of pituitary tumours between May 2017 and November 2018 (iMRI cohort). This cohort was compared with a pre-iMRI cohort of patients who underwent endoscopic resection of pituitary adenomas. Operative time, extent of resection, control of endocrine disease and post-operative complications were recorded and analysed. Thirty-seven patients were included in each cohort. iMRI facilitated additional tumour resection in 6/37 (16%) of cases. In 4/37 cases (11%), iMRI prompted a return to theatre but no further tumour could be identified. The overall GTR rate, following iMRI was 24/37 (65%) as compared to 21/37 (57%) in the pre-iMRI cohort. Cure of endocrine disease associated with hormonally active tumours was achieved in 9/11 (82%) of cases in the iMRI cohort. The mean operative time in the iMRI cohort was 327 minutes (five hours 27 minutes). 3 T iMRI provides immediate identification of residual tumour following endoscopic pituitary surgery. This allows for resection of surgically accessible residual disease during the same procedure and is likely to reduce the requirement for later re-intervention. However, the use of iMRI in this setting is associated with significant resource allocation issues which must be considered prior to the widespread adoption of this technique. [ABSTRACT FROM AUTHOR]

The aim of our study was to evaluate the efficacy and safety of Leksell gamma-knife radiosurgery in the treatment of residual growth hormone-secreting pituitary adenomas after the surgery. We conducted a retrospective analysis of 23 acromegaly patients treated with gamma-knife radiosurgery between 1996 and 2019. The therapeutic success of radiosurgery was defined as IGF-1 normalization without suppressive medication (complete response) or as IGF-1 normalization with medication (partial response). The median follow-up was 57 (10–198) months. Complete response was achieved in 11 patients (47.8%) with actuarial remission rates of 17.4%, 26.1%, 39.1% and 47.8% at 1, 2, 4, and 7 years, respectively. The median time to complete the response was 21 (6–85) months. Partial response was achieved in another nine patients (39.1%) after a median time of 48 (6–144) months from radiosurgery. Patients who achieved complete remission had significantly lower IGF-1 levels before radiosurgery (p = 0.016) as well as smaller tumour volume (p = 0.016) and radiologically less invasive tumours (p = 0.022) in comparison to patients who did not achieve IGF-1 normalization. Tumour growth control after radiosurgery was established in all patients. During the follow-up, new hormone deficiencies were found in seven patients (30.4%) which corresponds to the incidence of one new case of hypopituitarism per 7.1 patient years. Gamma-knife radiosurgery offers endocrine remission and tumour growth control in a substantial proportion of patients with GH-secreting adenomas. Given the high cost of life-long medical treatment and a moderate risk of radiation-induced side effects, radiosurgery for growth hormone-secreting pituitary adenomas should be considered in all patients with residual tumours. [ABSTRACT FROM AUTHOR]

See-saw nystagmus (SSN) is a rare form of nystagmus characterised by alternating elevation with incyclotorsion of one eye and concomitant depression with excyclotorsion of the other eye, often due to abnormalities involving the midbrain and parasellar region. Herein, we highlight a rare case of pendular SSN, which demonstrated complete resolution following resection of a pituitary macroadenoma. A patient in their 40s was identified to have SSN and was diagnosed with a pituitary macroadenoma. They underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma. Their nystagmus resolved immediately after surgery. From a review of the literature, resolution and/or significant improvement in SSN occurred in 74% of cases following treatment, with 100%, 86% and 50% following treatment for medication-induced, neurological infarcts, and mass-effect aetiologies of SSN, respectively. SSN is a rare entity with a wide array of aetiologies. Identification of the causative aetiology and appropriate treatment can lead to significant improvement or resolution of the nystagmus in most cases. [ABSTRACT FROM AUTHOR]

Introduction Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing's disease, high prolactin production, and without symptoms of hormone hypersecretion. Methods Previously published PitNET gene expression data was acquired from ArrayExpress. These data represented all secretion types. LR interactions were analyzed via a crosstalk score approach. Results Cortisol (CORT) ligand was significantly involved in tumor-to-tumor signaling across all PitNET subtypes but prolactinomas, which evidenced active CORT depletion. Likewise, CCL25 ligand was implicated in 20% of the top LR complex interactions along the tumor-to-stroma signaling axis, but silent PitNETs reported unique depletion of the CCL25 ligand. Along the stroma-to-tumor signaling axis, all clinical PitNET subtypes enriched stromal vasoactive intestinal polypeptide ligand interactions with tumor secretin receptor. All clinical PitNET subtypes enriched stromal DEFB103B (human β-defensin 103B) ligand interactions with stromal chemokine receptors along the stroma-to-stroma signaling axis. In PitNETs causing Cushing's disease, immune checkpoint ligand CD274 reported high stromal expression, and prolactinomas reported low stromal expression. Moreover, prolactinomas evidenced distinctly high stromal expression of immune-exhausted T cell response marker IL10RA compared with other clinical subtypes. Conclusion Relative crosstalk score analysis revealed a great diversity of LR complex interactions across clinical PitNET subtypes and between solid tumor compartments. More data are needed to validate these findings and exact clinical importance. [ABSTRACT FROM AUTHOR]

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level (p = 0.166), basal GH level (p = 0.001), and nadir GH level (p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission. [ABSTRACT FROM AUTHOR]

Cushing's disease (CD) is caused by rare pituitary corticotroph tumors that lead to corticotropin (ACTH) excess. Variants in FAF1 , a pro-apoptotic protein involved in FAS-induced cell death, have been implicated in malignant disorders but the involvement of FAF1 in pituitary tumors has not been studied. Genetic data from patients with CD were reviewed for variants in FAF1 gene. Knockout mice (KO) were followed to assess the development of any pituitary disorder or cortisol excess. AtT-20 cells were used to study the effects of the variants of interest on ACTH secretion and cell proliferation. Three variants of interest were identified in 5 unique patients, two of which had rare allele frequency in genomic databases and were predicted to be likely pathogenic. KO mice were followed over time and no difference in their length/weight was noted. Additionally, KO mice did not develop any pituitary lesions and retained similar corticosterone secretion with wild type. AtT-20 cells transfected with FAF1 variants of interest or WT expression plasmids showed no significant difference in cell death or Pomc gene expression. However, in silico prediction models suggested significant differences in secondary structures of the produced proteins. In conclusion, we identified two FAF1 variants in patients diagnosed with CD with a potential pathogenic effect on the protein function and structure. Our in vitro and in vivo studies did not reveal an association of FAF1 defects with pituitary tumorigenesis and further studies may be needed to understand any association. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) expression predict the biological behaviour, aggressiveness, and response to immune checkpoint inhibitors in different cancers. We reviewed the published data on PD-L1 expression in pituitary tumours from the perspective of its biological role and prognostic usefulness. Summary: A literature review focused on PD-L1 expression in pituitary tumours was performed. Six immunohistochemistry-based studies which assessed PD-L1 positivity in pituitary tumours were included, encompassing 704 patients. The cohort consisted of 384 (54.5%) nonfunctioning tumours and 320 (43.5%) functioning pituitary tumours. PD-L1 expression was positive in 248 cases (35.2%). PD-L1 positivity rate was higher in functioning than in nonfunctioning tumours (46.3% vs. 26.0%; p < 0.001) but also higher in growth hormone-secreting tumours (56.7%) and prolactinomas (53.6%) than in thyrotroph (33.3%) or corticotroph tumours (20.6%). While proliferative pituitary tumours showed higher rate of PD-L1 positivity than non-proliferative tumours (p < 0.001), no association with invasion or recurrence was found. Key Messages: PD-L1 is expressed in a substantial number of pituitary tumours, predominantly in the functioning ones. PD-L1 positivity rates were significantly higher in proliferative pituitary tumours in comparison to non-proliferative tumours, but no differences were found concerning invasive or recurrent pituitary tumours. More studies following homogeneous and standardised methodologies are needed to fully elucidate the role and usefulness of PD-L1 expression in pituitary tumours. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Craniopharyngioma is a rare epithelial brain tumor which arises from the embryological remnants of Rathke's pouch—a remnant of the primitive pharynx. The proximity of this tumor to the pituitary stalk, hypothalamus, third ventricle, optic chiasm, and optic nerves, as well as the major intracranial vessels bridging this area, makes safe surgical resection challenging. Given the recent advancement in endoscopic surgical techniques and the intraoperative assistance of neuronavigation and intraoperative magnetic resonance imaging, endoscopic endonasal transsphenoidal surgery (EETS) can be an alternative to the open transcranial approaches in the management of children with craniopharyngioma who fulfill the appropriate selection criteria. The comparison between the EETS and the open transcranial approach regarding the clinical and surgical outcomes could be subject to an inherent selection bias. In this article, we reviewed the body of the literature on the role of EETS in the management of pediatric craniopharyngioma and the proper selection criteria of children with craniopharyngioma, who might be suitable candidates for tumor resection via this minimally invasive endoscopic approach. We also looked at the preoperative assessment, surgical techniques, surgical and clinical outcomes, and the possible complications of endoscopic endonasal transsphenoidal surgery. [ABSTRACT FROM AUTHOR]

Background and Objectives: Prolactinomas are the most common pituitary adenomas, comprising 30–50% of such tumors. These adenomas cause hyperprolactinemia, leading to decreased fertility, reduced energy and libido, and galactorrhea. Diagnosing and treating prolactinomas in adolescents present unique challenges, as symptoms may be confused with age-related developmental variations. This case report explores the outcomes of early surgical intervention in an adolescent with a prolactinoma. Materials and Methods: A 14-year-old female presented delayed menarche and absent pubertal development. Initial evaluation revealed hyperprolactinemia (228.37 ng/mL) with normal estradiol levels. Initial management through observation was adopted, but persistent amenorrhea and severe headaches prompted further investigation. Magnetic resonance imaging revealed a cystic pituitary mass with apoplexy. Due to concerns regarding delayed puberty and the need for rapid normalization of prolactin levels, the patient underwent transsphenoidal surgery. Results: After operation, prolactin levels normalized, menarche occurred within three months, and secondary sexual characteristics developed within eight months. Pathology confirmed a pituitary adenoma with a high Ki-67 index (15%). Conclusions: Early surgical intervention for prolactinomas in adolescents can achieve successful biochemical remission and resolution of endocrine symptoms. Adolescents, particularly those with a high Ki-67 index and potential resistance to dopamine agonists, may benefit from prompt surgical management, resulting in improved clinical outcomes and complete tumor resection. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study explores the complex pathogenesis of pituitary adenomas (PAs), prevalent intracranial tumors in the pituitary gland. Despite their generally benign nature, PAs exhibit a diverse clinical spectrum involving hormone hypersecretion and varying invasiveness, hinting at multifaceted molecular mechanisms and abnormalities in tumorigenesis and gene regulation. Materials and Methods: The investigation focuses on the Ki-67 labeling index, SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 polymorphisms, alongside serum levels of SSTR2, SSTR5, and AIP, to discern their association with PAs. The Ki-67 labeling index was assessed using immunohistochemical analysis with the monoclonal antibody clone SP6, representing the percentage of tumor cells showing positive staining. Genotyping was performed via real-time polymerase chain reaction, and serum levels were analyzed using ELISA. The study included 128 PA patients and 272 reference group subjects. Results: The results derived from binary logistic regression analysis revealed an intriguing correlation between the SSTR2 rs2236750 AG genotype and approximately a 1.6-fold increased likelihood of PA occurrence. When analyzing SSTR5 rs34037914, statistically significant differences were found between Micro-PA and the reference group (p = 0.022). Additionally, the SSTR5 rs34037914 TT genotype, compared with CC + CT, under the most robust genetic model (selected based on the lowest AIC value), was associated with a 12-fold increased odds of Micro-PA occurrence. However, it is noteworthy that after applying Bonferroni correction, these findings did not retain statistical significance. Conclusions: Consequently, while this study hinted at a potential link between SSTR2 rs2236750 and pituitary adenoma development, as well as a potential link between SSTR5 rs34037914 and Micro-PA development, it underscored the need for further analysis involving a larger cohort to robustly validate these findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate the current situation of olfactory dysfunction in patients after endoscopic transsphenoidal resection of pituitary tumors, and analyze its influencing factors, to provide references for clinical nursing and rehabilitation. Methods: A cross-sectional study design and convenience sampling method were used to investigate 158 patients with pituitary tumors treated by endoscopic transsphenoidal pituitary tumor resection in the Department of Neurosurgery of three Grade-A general hospitals in Sichuan Province from January 2022 and June 2023. The olfactory function of patients was evaluated 1 week after surgery, and the general clinical data and olfactory related data of patients were collected, and the influencing factors of olfactory disorder were analyzed by logistic regression. Results: The incidence of olfactory dysfunction was 73.42%. analysis revealed that the formation of blood scabs, nasal cavity adhesion, cerebrospinal fluid leakage and operation time were independent risk factors for olfactory dysfunction in patients after transsphenoidal pituitary tumor resection (p < 0.05). Conclusion: The incidence of olfactory dysfunction is high in patients after endoscopic transsphenoidal resection of pituitary tumors, suggesting that medical staff should pay close attention to and identify patients with olfactory dysfunction based on the guidance of disease knowledge and skills, develop targeted nursing interventions, and promote the improvement of patients' olfactory function and quality of life. [ABSTRACT FROM AUTHOR]

Currently, cancer is a global concern with a focus on reducing its incidence and advancing diagnostic techniques. Faster and more precise cancer cell detection improves treatment and survival prospects. The objective of this study is to effectively categorize brain tumors with a specific focus on three types: meningioma, glioma, and pituitary tumors. The research adopts a thorough methodology encompassing pre-processing, feature extraction, feature selection, and classification using various techniques such as k-nearest neighbor (kNN), support vector machine (SVM), and Ensemble methods. Features were extracted using the bag of features- speeded-up robust features (BoF-SURF) algorithm for different cluster sizes (500, 250, 375, 750, and 825). Diverse feature selection algorithms, including ReliefF, analysis of variance (ANOVA), Kruskal Wallis, maximum relevance minimum redundancy (MRMR), and chi-square (CHI2), were employed to enhance detection accuracy. The proposed method, assessed on a public dataset comprising 3064 MRI scans of malignant brain tumours. The results of our experiments strongly support the effectiveness of our proposed method, achieving an impressive accuracy rate of 98.7%. Additionally, remarkable values of 98.4%, 98.5%, and 98.6% have been obtained for sensitivity, precision, and F1-score, respectively, when using the kNN classifier with 512 features selected from a cluster size of 750 using the ReliefF method. These outcomes clearly outperform existing approaches. [ABSTRACT FROM AUTHOR]

Background: Growth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels. Case presentation: We report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved. Conclusions: GH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the relationship between specific gene polymorphisms (TRAF2, TAB2, IKBKB) and protein levels and pituitary adenomas (PAs). The research included 459 participants, divided into a control group and a PA group. The key findings include significant differences in TRAF2 genotypes between the groups, with the G allele being less common in the PA group. The presence of the G allele and GG genotype were linked to a reduced risk of developing PAs, particularly microadenomas and macroadenomas. These results indicate a protective effect of the TRAF2 G allele against pituitary tumors. Aim: The aim of this study was to determine associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) gene polymorphisms and TRAF2, TAB2, IKBKB protein levels with clinical and morphological features of pituitary adenomas (PAs). Methods: This case–control study included 459 individuals divided into two groups: a control group (n = 320) and a group of individuals with PAs (n = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for TRAF2 (rs867186), TAB2 (rs237025), and IKBKB (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer's recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0". Results: We found significant differences in TRAF2 (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% (p < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, p < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA (p < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold (p < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model (p < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% (p < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, p < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% (p < 0.001), and the G allele was less common (13.7% vs. 34.2%, p < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold (p = 0.001), and each G allele reduced microadenoma odds by 3.1-fold (p < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model (p < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA (p < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold (p < 0.001), and each G allele reduced odds by 2.2-fold in the additive model (p < 0.001). Conclusions: The TRAF2 (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors. [ABSTRACT FROM AUTHOR]

Background: Resection of the medial wall of the cavernous sinus (MWCSR) is a growing surgical maneuver for the radical removal of pituitary adenomas. Method: We present a simple modification of the technique following the two dural layers of the floor of the sella turcica, allowing for early identification of the medial wall and simplifying dissection. We support this technique with an anatomical analysis on cadaveric specimens and clarifying dissection images. Conclusion: Recognition and dissection of the dural unfolding of the floor of the sella turcica are "key points" that lower the risk and facilitate the MWCSR. [ABSTRACT FROM AUTHOR]

Background: Large and giant pituitary adenomas (defined as tumors of maximal diameter ≥ 3–3.9 cm and ≥ 4 cm, respectively) present considerable surgical challenges regarding the extent of resection and perioperative morbidity. Endoscopic endonasal resection is considered the most effective treatment for pituitary adenomas. It allows for better visualization, maneuverability, and access to distant and lateral tumor compartments, ultimately enhancing the extent of resection. This article evaluates our initial experience with endoscopic endonasal resection of large and giant pituitary adenomas. The clinical outcomes, perioperative complications, and extent of tumor resection would be specifically addressed. Patients and methods: The primary goal of surgery was to decompress the optic pathways, and the secondary goals were to achieve maximal safe resection and hormonal control in hormone-secreting adenomas. The degree of tumor resection was classified as gross-total resection (100%), near-total resection (90–100%), subtotal resection (70–90%), and partial resection (< 70%). Results: 42 patients were included in this study. A good visual outcome achieved with 80% improvement in visual symptoms. Gross-total resection (GTR) was achieved in 19 patients (45.2%), near-total resection (NTR) was achieved in 12 patients (28.6%), subtotal resection (STR) in 6 patients (14.3%), and partial resection in the remaining 5 patients (11.9%). Subgroup analysis revealed that GTR, NTR rates were higher in large, compared to giant tumors. GTR, NTR rates of large adenomas were 59.3%, and 29.6%, compared to 20%, and 26.7% in giant adenomas respectively (p-value: 0.01428). Surgical complications were observed in 19 patients (45.2%) with CSF leakage being the most common complication (11 patients, 26.2%). Post-operative diabetes insipidus was observed in 5 patients (11.9%), major vascular injury in one case (2.4%), transient post-op 6th nerve palsy observed in 3 patients (7.1%), while two patients (4.8%) presented with post-operative paranasal sinuses infection. Conclusions: Endoscopic endonasal transsphenoidal resection of large and giant pituitary adenomas is a safe and efficient procedure. Large adenomas (3–3.9 cm) have excellent resection rates and lower complications than giant adenomas (≥ 4 cm), which may require extending our approach to achieve more tumor resection rates in the future. However, only adequate resection of these giant adenomas can be enough to achieve the main surgical goals of visual improvement, hormonal control, and decompression of surrounding structures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aggressive pituitary neuroendocrine tumors (PitNETs) present significant morbidity, and multimodal therapies including surgery, radiotherapy, and medications are frequently required. Chemotherapy, particularly temozolomide, is often pursued for tumors that progress despite these treatments. Although peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs is approved for the treatment of well-differentiated gastrointestinal neuroendocrine tumors, its use in aggressive PitNETs is limited. We describe the case of a 65-year-old man who presented with vision changes and hypopituitarism at age 33 secondary to a nonfunctioning gonadotroph PitNET. His initial treatment included a craniotomy followed by radiation therapy. With tumor regrowth, he required transsphenoidal surgeries at age 44 and age 52. At age 56, further tumor regrowth and a positive octreotide scan prompted treatment with long-acting octreotide for 1 year. Given absent tumor response, 12 cycles (4 treatment cycles and 8 maintenance cycles) of PRRT with 177Lutetium-DOTATATE were pursued. This resulted in partial response with significant tumor shrinkage. Notably, there was no tumor regrowth 40 months after treatment discontinuation. This is only the second report on the effectiveness of PRRT in patients with aggressive gonadotroph PitNETs. We also provide an overview of PRRT for PitNETs and describe clinical outcomes previously reported in the literature. [ABSTRACT FROM AUTHOR]

Blue nevus is a type of uncommon benign pigmented lesion in the skin or the mucosa of human body which is featured by pigmented dendritic melanocytes and spindled melanocytic cells. Sinonasal blue nevus is extremely rare. We reported a sinonasal blue nevus case with the background of pituitary adenoma, type 2 diabetes mellitus, and hypertension (including endoscopic and histological pictures). Further, the existing literature about blue nevus is reviewed. This paper puts a spotlight on the potential correlation between blue nevus with the endocrine system disorder and provides support for further experimental research. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare disease involving multiple systems, and it is caused by excessive proliferation of Langerhans cells. The hypothalamic-pituitary region (HPR) is involved in 5%-50% of all LCH patients, particularly those with multifocal disease. Diabetes insipidus (DI), the most common endocrinal abnormality, occurs in 15%-50% of patients with HPR-LCH. Anterior pituitary deficiency occurs in the minority, in 5%-20% of the patients, usually in combination with DI. The disease is clinically heterogeneous. The most commonly involved organs are the skeleton (78.7%) and skin (36.7%). Involvement of multiple organs such as the skin, lymph nodes, lungs, spleen, liver, bone marrow, ear, nose, and throat is a criterion for poor prognosis. We report a 19-year-old woman who presented with a pituitary suprasellar mass, had anterior pituitary deficiency (APD) but no DI at the time of diagnosis, and had the ear and mastoid bone involvement. We initially did not consider LCH but diagnosed it later. In the literature, we found only 2 cases with APD but without DI among patients with an LCH diagnosis. The clinical features of HPR-LCH are similar to other hypothalamicpituitary disorders; thus, differential diagnosis is necessary. Accurate and rapid diagnosis is crucial for HPR-LCH; its symptoms are progressive and irreversible. Unlike other disorders of HPR, LCH is treated with chemotherapy. Necessary surgical interventions must be performed to make a rapid pathologic diagnosis. [ABSTRACT FROM AUTHOR]