Pituitary Adenomas Research Articles

Headache in pituitary adenomas: frequency, characteristics and outcome after treatment

Headache in pituitary adenomas: frequency, characteristics and outcome after treatment

Descriptive analysis and outcomes of PitNETs treated surgically during pregnancy and postpartum.

Data on pituitary neuroendocrine tumors (PitNETs) surgically treated during pregnancy is limited, and no studies have compared these cases to those treated in non-pregnant women. This study aimed to describe the clinical, radiological, and histological profiles of patients treated surgically for PitNETs during pregnancy and evaluate long-term prognosis. This study was multicentric, observational and retrospective. We included 10 patients from 5 university hospitals who underwent surgical treatment for PitNETs during pregnancy or within 12 months postpartum, along with 30 matched non-pregnant controls treated surgically for PitNETs. Clinical and histological data, as well as progression-free survival without additional treatment, were compared between pregnant and non-pregnant patients. Among the 10 PitNETs, 4 were corticotropic, 2 gonadotropic, 2 lactotropic, and 2 somatotropic. The primary surgical indication (tumour syndrome with or without failure of medical treatment) was similar between the two groups: 7/10 vs 19/30 (p = 1.00). There was no statistically significant difference in volume (p = 0.072) or radiological invasion markers (optic chiasm compression, p = 0.059, and cavernous sinus invasion, p = 0.274). However, PitNETs in pregnant women showed higher mitotic activity (p = 0.038) and were more frequently classified as grade 2b (Trouillas clinicopathological classification; p=0.049). The need for second-line treatment was also more frequent (p = 0.005). PitNETs requiring surgical treatment during pregnancy are characterized by increased proliferative activity and progression after surgery. Despite this, the long-term prognosis remains favorable. These results need confirmation in a larger study.

Pituitary Adenomas in Children: : Specific Imaging Features According to Hormonal Secretion.

Pituitary adenomas are much rarer in children than in adults. We aimed to analyze their imaging characteristics in this age group and to compare them according to the hormonal secretion. We conducted an observational monocentric retrospective study on clinical and imaging data. We analyzed imaging features before surgery or drug treatment of pituitary adenomas in children confirmed by histopathology or hormonal secretion. We assessed tumoral signal intensity, volume and aggressiveness, and compared it according to the hormonal secretion. We included 31 children (13 lactotroph (42%), 8corticotroph (26%), 5somatotroph (16%), 5plurihormonal adenomas (16%) including 1 non-secreting macroadenoma) with a median age of 13years (range 2-16years-old), without age or sex difference between secretion types. Lactotroph and somatotroph adenomas were larger than corticotroph adenomas (p = 0.007) and were more aggressive (p = 0.01). They also had higher signal intensity on T2-weighted images (p = 0.04). T1 signal intensity was similar between the groups on pre and post-contrast images (lower enhancement than the normal pituitary). No non-secreting micro-adenoma became clinically significant enough to lead to a pathological confirmation or specific treatment. Genetic research was conducted on 20children, finding MEN1 mutations in 80% of the patients. Pituitary adenomas in children are rare but should be considered when facing similar imaging features than in adults. Imaging characteristics may allow to suspect the hormonal secretion.

Machine Learning Prediction of Pituitary Macroadenoma Consistency: Utilizing Demographic Data and Brain MRI Parameters.

Consistency of pituitary macroadenomas is a key determinant in surgical outcomes, with non-soft consistency linked to more complications and incomplete resections. This study aimed to develop a machine learning model to predict the consistency of pituitary macroadenomas to improve surgical planning and outcomes. A retrospective study of patients with pituitary macroadenomas was conducted. Data included brain magnetic resonance imaging findings (diameter and apparent diffusion coefficient), patient demographics (age and sex), and tumor consistency. Seventy patients were evaluated, 59 with soft consistency and 11 with non-soft consistency. The support vector machine (SVM) was the best model with ROC AUC score of 83.3% [95% CI 65.8, 97.6], AP AUC of 69.8% [95% CI 41.3, 91.1], sensitivity of 73.1% [95% CI 44.4, 100], specificity of 89.8% [95% CI 82, 96.7], F1 score of 0.63 [95% CI 0.36, 0.83], and Matthews correlation coefficient score of 0.57 [95% CI 0.29, 0.79]. These findings indicate a significant improvement over random classification, as confirmed by a permutation test (p < 0.05). Additionally, the model had a 67.4% probability of outperforming the second-best model in cross-validation, as determined through Bayesian analysis, and demonstrated statistical significance (p < 0.05) compared to non-ensemble models. Using explainability heuristics, both 2D and 3D probability maps highlighted areas with a higher probability of non-soft consistency. The attributes most influential in the correct classification by our best model were male sex and age ≤ 42.25years. Despite some limitations, the SVM model showed promise in predicting tumor consistency, which could aid in surgical planning. To address concerns about generalizability, we have created an open-access repository to promote future external validation studies and collaboration with other research centers, with the goal of enhancing model prediction through transfer learning.

Overlapping presentations and diverse genetic defects characterize neuroendocrine neoplasms in a Mexican cohort.

Genetic tests are part of the routine clinical approach to syndromic and nonsyndromic phenotypes of neuroendocrine neoplasms (NENs). Current data on phenotype-genotype associations in NENs, however, do not accurately represent all populations. To describe the frequency, inventory, and clinical associations of germline defects associated with multiple types of NENs in a Mexican cohort. Blood DNA from Mexican adults with NENs was analyzed with a 53-gene NGS panel developed ad hoc (n=90) or Sanger sequencing (n=2). Single nucleotide variants, indels and structural variants were identified, classified, and subjected to orthogonal confirmation. When possible, tumor samples and blood DNA from additional family members were tested using Sanger sequencing. Ninety-two probands (70.7% women, 51.5% sporadic) were included; sixteen carried pathogenic or likely pathogenic (P/LP) variants and were significantly younger at disease onset, compared with the rest (29.6±10,7 vs. 40 [21.5-51.5] years, P=0.0384). Likely driving variants were identified in three-quarters of Von Hippel Lindau syndrome cases, one-third of multiple endocrine neoplasia type 1 (MEN1), one-quarter of early-onset acromegaly/gigantism, and individual cases of Cushing's disease, MEN2A, and medullary thyroid carcinoma. One patient with clinical MEN1 associated with an SDHA variant and one with a pituitary tumor and neurofibromatosis type 1 were also identified. Probands with familial disease were more likely to carry P/LP variants, compared with sporadic cases (26.7 vs 8.5%, P=0.0282). P/LP variants were identified in 17.4% of individuals with NENs. Our research provides a view of the landscape of NEN drivers in a population not previously characterized.

Preoperatively Predicting PIT1 Expression in Pituitary Adenomas Using Habitat, Intra-tumoral and Peri-tumoral Radiomics Based on MRI.

The study aimed to predict expression of pituitary transcription factor 1 (PIT1) in pituitary adenomas using habitat, intra-tumoral and peri-tumoral radiomics models. A total of 129 patients with pituitary adenoma (training set, n = 103; test set, n = 26) were retrospectively enrolled. A total of 12, 18, 14, 13, and 14 radiomics features were selected from the ROIintra, ROIintra+peri (ROIintra+2mm, ROIintra+4mm, ROIintra+6mm), and ROIhabitat, respectively. Then, three machine learning algorithms were employed to develop radiomic models, including logistic regression (LR), support vector machines (SVM), and multilayer perceptron (MLP). The performances of the intra-tumoral, combined intra-tumoral and peri-tumoral, and habitat models were evaluated. The peritumoral region (ROI2mm, ROI4mm, ROI6mm) of the combined model with the highest performance was individually selected for further peritumoral analysis. Moreover, a deep learning radiomics nomogram (DLRN) was constructed incorporating clinical characteristics and the peri-tumoral and habitat models for individual prediction. The combined modelintra+2mm based on ROIintra+2mm achieved a better performance (AUC, 0.800) than that of the intra-tumoral model alone (AUC, 0.731). And the habitat model showed a higher performance (AUC, 0.806) than that of the intra-tumoral model. In addition, the performance of the peri-tumoral model based on ROI2mm was 0.694 in the testing set. Furthermore, the DLRN achieved the highest performance of 0.900 in the test set. The DLRN showed the best performance for PIT1 expression in pituitary adenomas, followed by the habitat, combined modelintra+2mm, intra-tumoral model, and peri-tumoral model based on ROI2mm, respectively. These different models are helpful for the model choice in clinical work.

Association of pituitary neuroendocrine tumors and neurofibromatosis type 1: assessing causation versus coincidence. Case report

IntroductionPatients with neurofibromatosis type 1 (NF1) are at risk for developing various neoplasms. Since the early twentieth century, multiple cases of pituitary neuroendocrine tumors (PitNETs) occurring in this context have been published. Yet, the role of NF1 (17q11.2) loss-of-function (LOF) variants in pituitary tumorigenesis remains unclear.AimWe report the clinical and molecular characterization of a case of PitNET diagnosed in a patient with NF1. We also review the available data for and against a causal association between NF1 defects and pituitary tumors.MethodsOur patient was recruited via an ongoing prospective study of individuals with neuroendocrine neoplasms. Genetic testing was carried out by means of targeted next generation sequencing (NGS) and Sanger sequencing in blood and tumor DNA, respectively. NF1 expression was analyzed via quantitative polymerase chain reaction (qPCR) in blood and tumor cDNA. Similar cases were searched in the literature.ResultsA 54-year-old-man was incidentally diagnosed with a clinically non-functioning PitNET via brain imaging. He had a personal and family history of NF1 and carried the germline pathogenic variant NF1 (NM_001042492.3): c.147C&amp;gt;A, p.Y49*. Via transsphenoidal surgery, a 16 mm lesion was resected, showing strong granular cytoplasmic immunoreactivity with patchy distribution for NF1 and preserved heterozygosity for the NF1 defect. Additional NGS ruled out germline defects in PitNET-associated genes. By qPCR, NF1 was significantly overexpressed in the tumor when compared with another NF-PitNET, but not when compared with a corticotropinoma. We reviewed twenty-three case reports of PitNETs occurring in patients with either clinical NF1 without genetic study, individuals with NF1 germline variants with or without clinical NF1 or associated with somatic NF1 defects. Predominance of GH-secreting and large PitNETs, with young-onset in around half of the cases, were noticed. Two individuals developed multiple endocrine neoplasia-like phenotypes but tested negative for other relevant genetic defects.ConclusionsAlthough the association of NF1 and PitNETs could be coincidental, the clinical characteristics of the reviewed cases differ from those of typical incidentalomas. NF1 could drive pituitary tumorigenesis via haploinsufficiency, but this hypothesis requires further research. Additional clinical and molecular data from large cohorts of affected individuals should help clarify this question.

Clinical and rehabilitation aspects of managing patients with meningiomas, schwannomas, ependymomas, and pituitary neuroendocrine tumors

The rehabilitation of neurooncology patients represents a critical issue due to the high incidence of brain tumors of varying locations and the severity of associated neurological symptoms, which significantly reduce the patient’s quality of life. Over the past decades, the prevalence of central nervous system tumor has increased by more than twofold in individuals aged 65 and above. Neurooncology patients represent a complex group that requires long-term restorative treatment. The early initiation of rehabilitation facilitates the recovery of impaired functions prior to the formation of persistent pathological patterns. This article examines neurorehabilitation methods using the example of the most common benign brain tumors, which include meningiomas, schwannomas, ependymomas, and pituitary neuroendocrine tumors. Significant advancements have been made in the treatment of these tumors in recent years, particularly through combined treatment modalities. A multidisciplinary approach to neurooncology is becoming increasingly recognized as a key element in global healthcare. However, the needs of these patients and their families extend beyond medical care, necessitating the involvement of psychologists, occupational therapists, speech-language pathologists, and social workers. A comprehensive approach to treatment, early restorative interventions and the development of innovative neurorehabilitation methods can facilitate a personalized strategy for patients with benign brain tumors, thereby increasing their rehabilitation potential.

Growth hormone signaling and clinical implications: from molecular to therapeutic perspectives.

Growth hormone (GH) is a key polypeptide hormone secreted by somatotroph cells in the anterior pituitary gland, essential for postnatal growth, metabolism, and systemic homeostasis. Its secretion is regulated by hypothalamic neuropeptides, including GH-releasing hormone and somatostatin. GH exerts effects through direct interaction with the growth hormone receptor and indirect pathways mediated by the GH-IGF-I axis. GHR activation triggers signaling pathways, such as JAK-STAT, PI3K/AKT, and MAPK, promoting cellular proliferation, differentiation, and metabolic balance. The GH-IGF-I axis is critical for bone growth, lipid and carbohydrate metabolism, and organ-specific physiological functions. Dysregulation of GH results in diverse disorders. Congenital deficiencies, like isolated GH deficiency and syndromic conditions (e.g., Turner syndrome), stem from genetic mutations. Acquired deficiencies arise from trauma, tumors, infections, or autoimmune damage, while GH overproduction causes gigantism in children and acromegaly in adults, often due to pituitary adenomas. Idiopathic deficiencies, lacking identifiable causes, complicate management further. Advances in therapy have transformed outcomes for GH disorders. Recombinant human growth hormone provides effective replacement therapy for deficiencies. Somatostatin analogs, dopamine receptor agonists, and GH receptor antagonists are pivotal for managing GH excess. Surgical and radiotherapeutic interventions remain essential for pituitary adenomas. However, GH therapy requires close monitoring to prevent side effects like insulin resistance and metabolic complications. This review provides a comprehensive evaluation of the molecular mechanisms underlying GH action, its physiological roles, GH-related disorders, and therapeutic approaches to optimize patient outcomes.

Cabozantinib in the Treatment of Neuroendocrine Neoplasms: Insights Across Different Tumor Origins.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from neuroendocrine cells, exhibiting a wide range of behaviours from indolent to highly aggressive forms. Treatment options remain limited, particularly for progressive cases. Cabozantinib, a multitarget tyrosine kinase inhibitor, has demonstrated potential in targeting key pathways related to tumor growth, angiogenesis, and metastasis. This review provides a comprehensive analysis of cabozantinib's therapeutic role across various NEN subtypes, including gastroenteropancreatic NENs, lung NENs, pheochromocytomas/paragangliomas, Merkel cell carcinoma, presacral NENs, pituitary neuroendocrine tumors, and neuroendocrine prostate cancer. The paper discusses several preclinical and clinical studies that demonstrate the efficacy of cabozantinib in slowing tumor progression and improving progression-free survival, particularly in patients with progressive, well-differentiated NENs. However, cabozantinib's complex toxicity profile limits its broad application, necessitating further research to optimize dosing, particularly in syndromic NENs. Ongoing trials are investigating cabozantinib in combination with somatostatin analogues, peptide receptor radionuclide therapy, temozolomide and immunotherapies in order to overcome treatment resistance and expanding therapeutic strategies for advanced NENs.

Fractionated robotic radiosurgery for unfavorable nonfunctioning pituitary macroadenoma: 5-year outcomes from a single institution protocol

ObjectiveNonfunctioning macroadenoma is a commonly diagnosed pituitary tumor. Resection is the favored treatment, with radiosurgery often utilized for residual or progressing disease. Long-term outcomes are established in the literature for single-fraction frame-based radiosurgery, but mature outcomes are lacking for fractionated frameless radiosurgery. We report our institution’s 5-year efficacy and toxicity results for unfavorable nonfunctioning pituitary macroadenoma patients treated with 5-fraction robotic radiosurgery.MethodsBetween 2010 and 2020, patients who completed 5-fraction robotic radiosurgery for the treatment of unfavorable nonfunctioning pituitary macroadenomas were included. A tumor was considered unfavorable if the gross tumor volume (GTV) was larger than 5 cc or if it closely approached a critical structure (optic apparatus, brainstem, or pituitary gland). Local control was calculated using the Kaplan–Meier method.ResultsTwenty predominantly female patients (60%), ages 21–77 (median: 53 years), were included in this study. All underwent primary resection at the time of diagnosis. The indication for radiosurgery was tumor progression (n = 14, 70%) or residual tumor after subtotal resection (n = 6, 30%). Eighty-five percent of patients treated with radiosurgery (n = 17) had cavernous sinus involvement. Median GTV was 3.4 cm3 (range: 0.3–20.8 cm3), and 40% of the tumors had suprasellar extension. A mean dose of 28.8 Gy (range: 25–30 Gy) was delivered to a median isodose line of 80% (range: 75%–89%). The median optic chiasm maximum point dose was 21.8 Gy (range: 12.0–25.0 Gy). Acute toxicity was minimal with eight patients (40%) developing short-lived headaches and one patient (5%) developing a brief ipsilateral sixth nerve palsy. There was no late radiation-induced neurologic or optic dysfunction identified in this cohort. At a median follow-up of 5 years, local control was 94%. There was one in-field failure pathologically confirmed following surgery for pituitary hemorrhage and two radiographically confirmed out-of-field failures in patients with larger tumors (&amp;gt;20 cc).ConclusionsThe treatment of unfavorable nonfunctioning pituitary macroadenoma with 5-fraction robotic radiosurgery provides excellent local control to date, with acceptable toxicity. However, tumors with GTVs greater than 20 cc may still require conventionally fractionated treatment with a margin to optimize local control.

Exploring the Role of Intraoperative Prolactin Levels in Surgical Management of Prolactinomas: Predicting Operative Success and Enhancing Surgical Decision-Making

Objective: Prolactinomas comprise half of all pituitary adenomas. This study explores the significance of measuring intraoperative (IO) prolactin (PRL) levels in guiding surgical decision making and predicting operative success. Methods: Retrospective cohort study design of consecutive patients with prolactinomas who underwent TSS resection from June 2021 to May 2023. Intraoperative prolactin was measured after tumor resection was completed. Remission was defined as normalization of prolactin levels during follow-up without medication. Outcomes included factors associated with remission, utilizing significance thresholds at p&lt;0.05. Results: Thirteen patients were included with a 5.3-month median follow-up (range, 3-15 months). Most of the tumors were microadenomas (61%), with a median preoperative PRL level of 116 ng/mL (range, 25-471 ng/mL). Gross total resection (GTR) was achieved in 69% of patients, all of whom attained remission. The median IO PRL was 19.8 ng/mL (range, 1-329), the postoperative day 1 (POD1) PRL of 3.6 ng/mL (range, 1-203 ng/mL) and the latest PRL at 9.3 ng/mL (range, 1-137 ng/mL). A ≥40% decline in IO PRL from baseline was identified as the optimal cut-off for predicting biochemical remission, with 89% sensitivity, 75% specificity, and 85% accuracy. Conclusions: Monitoring prolactin levels intraoperatively may be a useful biomarker aiding surgeon’s assessment of the extent of tumor resection and guiding surgical decision-making. Further refinement of the immunoassay assay and clinical testing with more extensive prospective studies are needed.

Giant and irregular pituitary neuroendocrine tumors surgery: comparison of simultaneous combined endoscopic endonasal and transcranial and purely endoscopic endonasal surgery at a single center

BackgroundSurgical management of giant and irregular pituitary neuroendocrine tumors (GIPitNETs) presents a significant challenge in neurosurgery. While endoscopic endonasal surgery (EES) is a widely used approach for PitNETs, GIPitNETs with extensive intracranial extension pose challenges for purely EES. We use simultaneous combined endoscopic endonasal and transcranial surgery (CECS) for the treatment of this type of tumor. Currently, there is limited research comparing CECS to EES for GIPitNETs. This study aims to compare the efficacy and short outcome of CECS and purely EES in the management of GIPitNETs to better understand the advantages and limitations of each surgical approach.MethodsThe data of GIPitNETs patients who underwent surgery between March 2018 and May 2023 at a single center were retrospectively reviewed. All included cases were divided into CECS and EES groups according to the treatment modality received. The baseline characteristics and tumor imaging features of patients were compared between the groups, as well as surgical results, perioperative complications, and last follow-up outcomes.ResultsA total of 50 patients met the inclusion criteria, with 27 undergoing CECS and 23 EES. CECS achieved a significantly higher GTR rate compared to EES (66.7% vs. 13.0%, p < 0.0001). CECS had longer operation times and hospital stays, but both approaches had similar rates of complications, including intracranial infection, CSF leakage, new pituitary dysfunction, postoperative diabetes insipidus, and vascular infarction. CECS reduces the risk of postoperative bleeding. Tumor recurrence and reoperation were significantly more common in the EES group.ConclusionsCECS is a safe and effective surgical approach for GIPitNETs, leading to higher rates of GTR, comparable complication rates, and reduced risk of postoperative bleeding when compared to purely EES. EES was associated with more tumor recurrence. Further long-term follow-up data is needed to validate these findings.

Etiology, presentation, and outcomes of hyperprolactinemia due to pituitary masses in children and adolescents.

Hyperprolactinemia in children and adolescents can result from various etiologies, including pituitary masses. Understanding the underlying causes, clinical presentation, and outcomes is essential for effective management. A retrospective cohort study was conducted, analyzing clinical data from patients diagnosed with hyperprolactinemia secondary to pituitary masses. The study included patients aged under 18 years, who were diagnosed between January 2018 and September 2024. Patients were classified into two groups: those with prolactinoma and those with non-prolactinoma causes, including non-functioning pituitary adenomas (NFPAs) and craniopharyngiomas. Serum prolactin levels, imaging studies, and treatment responses were assessed. A total of 33 patients with hyperprolactinemia attributed to pituitary masses were identified. The diagnoses among the patients were as follows: 54.5% had prolactinomas, 24.2% had NFPAs, and 21.2% had craniopharyngiomas. The age at diagnosis ranged from 8.4-17.9 years. In the prolactinoma group, the mean age at diagnosis was 15.6 ± 2.1 years, while in the non-prolactinoma group, it was 13.5 ± 2.9 years, and a statistically significant difference was observed (p = 0.024). The median prolactin level was 258 ng/mL (range: 30.5-14,35 0 ng/mL). According to the diagnoses, the median prolactin level was 491.5 ng/mL (range: 249-14,350 ng/mL) for prolactinomas, 45.6 ng/mL (range: 30.5-68.5 ng/mL) for NFPAs, and 61 ng/mL (range: 44-72 ng/mL) for craniopharyngiomas. Menstrual irregularities, headaches, and galactorrhea were the most commonly reported complaints. Overweight/obesity was present in 39.3% of the entire cohort, while patients with prolactinomas demonstrated a significant reduction in BMI SDS following cabergoline treatment. Cabergoline treatment achieved a 100% success rate in patients with prolactinomas. We observed a higher prevalence of hyperprolactinemia due to NFPAs and craniopharyngiomas compared to previous reports. Notably, obesity was prevalent among patients and demonstrated a favorable response to cabergoline therapy. These findings emphasize the necessity for future studies, particularly larger prospective trials incorporating genetic analyses, to enhance our understanding of the characteristics and treatment outcomes of pediatric hyperprolactinemia.

Morphometric Analysis of Radiological Features of Pituitary Tumors and Optic Pathway Distortion Associated with Visual Impairment in Pituitary Macroadenomas with Suprasellar Extension

To validate the correlation between visual impairment (VI) and suprasellar extension (SSE) in pituitary macroadenomas and to identify patients at heightened risk of preoperative visual deficits by analyzing anatomical distortion of optic nerve and optic chiasm (OC) using preoperative magnetic resonance imaging. Ninety-seven patients with pituitary macroadenomas and SSE, treated between January 2015 and April 2022, were analyzed. Associations between VI, demographic data, SSE, and optic pathway deformation were assessed. SSE cutoff points for predicting VI were determined using receiver operating characteristic curves, with univariate and multivariate logistic regression identifying potential risk factors. Of the 97 patients, 47 had confirmed VI. Independent predictors of VI included visual symptoms lasting >1month, sagittal SSE >10.35mm, and vertical OC width >5.6mm. Additional risk factors were older age, nonfunctioning pituitary adenoma, coronal SSE, dumbbell-shaped tumors, large and giant adenomas, reduced optic nerve diameter, increased horizontal OC width, and thinned OC thickness. Tumor morphology and optic pathway distortion predict preoperative VI in patients with pituitary macroadenomas. These findings support the development of a viable approach for assessing VI risk in clinical practice, aiding in decisions regarding optimal surgical timing.

Role of Cathepsin K in bone invasion of pituitary adenomas: A dual mechanism involving cell proliferation and osteoclastogenesis.

This study aimed to investigate the regulation and underlying mechanism of Cathepsin K (CTSK) in bone-invasive pituitary adenomas (BIPAs). A total of 1437 patients with pituitary adenomas were included and followed up. RNA sequencing, immunohistochemistry, and qRT-PCR were used to analyze CTSK expression. The effects of CTSK on cellular proliferation, bone matrix degradation, and osteoclast differentiation were determined by gain/loss of function experiments in vitro and in vivo. The exploration of signaling pathways was determined through molecular biology experiments. Here, we reported a significant fraction (∼10%) of pituitary adenoma patients developed bone invasion, which was correlated with tumor recurrence. Patients with BIPAs had shorter recurrence-free survival. CTSK expression was increased in BIPA patients and was strongly associated with a worse prognosis. Increased CTSK expression enhanced pituitary adenoma cell proliferation through the activation of the mammalian target of rapamycin (mTOR) signaling pathway and promoted bone invasion by increasing osteoclast differentiation both in vitro and in vivo. Treatment with the CTSK inhibitor odanacatib effectively inhibited pituitary adenoma cell proliferation and bone invasion in these models. Additionally, CTSK facilitated osteoclast differentiation by promoting RANKL expression in MC3T3-E1 cells via interaction with TLR4. Based on these findings, we conclude that CTSK has the potential to become a novel predictive biomarker and therapeutic target for BIPAs.

Endoscopic Endonasal Approach for Calcified Sellar/Parasellar Region Pathologies: Report of 11 Pituitary Adenoma Cases

Calcification in pituitary adenomas is a rare occurence and its differential diagnosis typically includes other sellar masses.Common calcifications in pituitary adenomas are classified into two morphological forms: capsular(eggshell-like)and multiple small nodular calcifications located within the adenoma.Also,there is a pituitary stone term.This study aims to present the results of calcified pituitary adenoma case series who underwent endoscopic endonasal approach(EEA)and the clinical,histopathological characteristics and surgical outcomes of these cases. This study conducted a retrospective cohort analysis of patients with calcified pituitary adenoma operated on by EEA between August 1997 and February 2024.The inclusion criteria were as follows:proven radiological calcification on pre-operative neuroimaging,intraoperative findings of calcification and definitive histopathological diagnosis of calcification.Among these patients,11 cases were included. The mean follow-up duration was 51.45±37.24 (6-118)months.Based on the pre-operative paranasal sinus computed tomography(CT)scans of patients,nine patients(81.8%)had intratumoral calcification,one(9.1%)had capsular(eggshell like)calcification and one(9.1%)had both intratumoral and capsular calcification.Moreover,stone-like calcifications were observed in four patients(36.4%),soft type calcifications in three(27.3%),hard-type calcifications in three(27.3%)and soft and hard-type calcifications in one(9%).Gross total resection(GTR)was achieved in nine patients(81.8%).Pathologic subtypes included non-functioning(n = 4),prolactin secreting(n = 3),growth hormone secreting adenoma(n = 2)and pituitary apoplexy(n = 2).Ten patients had psammomatous type calcifications and one had extensive ossification and osteoid metaplasia. Pre-operative radiological evaluation,intraoperative classification of calcification,and post-operative histopathological assessments are crucial in the treatment of calcified adenomas.Bases on these findings,the EEA,with its advantages,is an approach that can be effectively used in the management of these calcified adenomas.

Aggressive Pituitary Adenomas: Clinical Predictors for Rapidly Recurrent Pituitary Adenomas—Looking Beyond Proliferative Markers

Aggressive Pituitary Adenomas: Clinical Predictors for Rapidly Recurrent Pituitary Adenomas—Looking Beyond Proliferative Markers

Does the crafted abdominal fat grafting technique completely eliminate risk of postoperative CSF leak in endonasal pituitary surgery? Technical note and preliminary clinical outcome.

The endonasal transsphenoidal approach (ETA) developed over the years has become the standard of care for sellar and parasellar lesions. However, because it necessitates the removal of the skull base bone, it is often accompanied by CSF leakage. The authors aimed to provide technical nuances and analyze the results of their routine fat grafting technique after ETA. A consecutive patient cohort (2004-2024) of 168 patients who underwent ETA for sellar and parasellar lesions and the modified fat grafting technique for skull base repair were retrospectively reviewed. Overall, combined ETA and transcranial approach (TCA) was performed in 7 (4.2%) patients, and 4 (2.4%) patients had prior transsphenoidal surgery. The size of the lesion was < 10 mm in 24 (14.3%) patients, 10-30 mm in 93 (55.4%), and > 30 mm in 51 (30.4%). Histopathological diagnoses were as follows: 154 (91.7%) pituitary adenomas, of which 45 (26.8%) were secreting; 8 (4.8%) Rathke's cleft cysts; 2 (1.2%) inflammatory/autoimmune lesions; 2 (1.2%) craniopharyngiomas; 1 (0.6%) renal cell carcinoma metastasis; and 1 (0.6%) chordoma. Gross-total resection was achieved in 127 (75.6%) patients, near-total resection in 22 (13.1%), and subtotal resection/partial resection/biopsy in 19 (11.3%). Overall, 122 (72.6%) procedures had intraoperative CSF leakage. Postoperative CSF leakage was observed in 1 (0.6%) patient treated with a revision operation and regrafting with a slightly larger graft and lumbar drainage. Even slight modifications in contemporary surgical techniques and the addition of an innovative approach may improve the treatment of sellar and parasellar lesions via ETA and reduce the risk of CSF leakage. The authors have developed and described a modified fat grafting technique with gradual crafting and preprocessing of the abdominal fat tissue for skull base repair, and they have demonstrated its effectiveness in significantly reducing the CSF leak rate. This technique enables adequate reconstruction of skull base defects with low donor-site complication rates and obviates the need for external lumbar drainage.

Older Patients with Pituitary Adenomas Are More Likely to Present with Vision Loss

Older Patients with Pituitary Adenomas Are More Likely to Present with Vision Loss