Acquired hypothalamic obesity: A clinical overview and update.

Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.

[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

Microsurgical Resection of a Parachiasmatic Craniopharyngioma via a Left-Sided Pterional Transsylvian Approach.

Craniopharyngiomas are histologically benign tumors that originate from squamous rests along the pituitary stalk. They make up approximately 1.2% to 4.6% of all intracranial tumors and do not show significant differences in occurrence based on sex. Adamantinomatous craniopharyngiomas have 2 peaks of incidence, commonly observed in patients from ages 5 to 15 years and again from 45 to 60 years. In contrast, papillary craniopharyngiomas mainly affect adults in their fifth and sixth decades of life.1 The "malignancy" of craniopharyngiomas is attributed to their location and the challenges associated with achieving complete removal because they can manifest in the sellar, parachiasmatic, and intraventricular regions or a combination of these.2,3 Various approaches have been used to resect these tumors.4,5 Radical resection offers the most promising option for disease control, potential cure, and the ability to transform the disease from lethal to survivable in children, allowing for a functional adult life.2,3 Meticulous evaluation is crucial to determine the appropriate approach and side, with particular emphasis on closely examining the relationship between the tumor and optic pathways (nerve, chiasm, tract), which are frequently involved. This assessment should also include the tumor's relationship with other crucial structures, such as the hypothalamus and adjacent arteries, to ensure that the strategy is adjusted accordingly to further minimize the risk of postoperative morbidity. Video 1 demonstrates a left-sided pterional transsylvian approach to remove a parachiasmatic craniopharyngioma involving the left optic chiasm and tract.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

The Role of Tumor-Associated Hypothalamic Involvement in Surgical Treatment and Long-Term Outcome in Adult Patients with Craniopharyngioma.

INTRODUCTION: Hypothalamic invasion in pediatric patients with craniopharyngioma negatively influences clinical outcomes. It has been shown that radiologic classification of hypothalamic invasion can effectively predict surgical strategies to minimize postoperative comorbidities in pediatric patients. However, no comparative analysis has been performed in adult patients with craniopharyngioma. This study implements the previously established radiologic classification to characterize postoperative morbidity, surgical outcome, and distress in adult patients with craniopharyngioma. METHODS: Electronic medical records of 22 adult patients with craniopharyngioma were used to analyze patient demographics, surgical data, endocrinologic and ophthalmologic status, and histopathology in a retrospective single-center study. Questionnaires regarding postoperative distress (National Comprehensive Cancer Network Distress Thermometer and Problem List), comorbidities (Charlson Comorbidity Index), employment status, and need for supportive care were distributed. Magnetic resonance imaging scans were categorized according to Puget et al. RESULTS: Patients with hypothalamic involvement show significantly higher rates of postoperative diabetes insipidus and higher scores on the National Comprehensive Cancer Network Distress Thermometer. This significant difference was lost when considering postoperative Puget grades. Puget grades 1 and 2 were found to be associated with the use of a subfrontal surgical approach (hazard ratio, 4.080; confidence interval, 1.153-14.431; P = 0.029). CONCLUSIONS: Our results point toward a possible predictive role of preoperative hypothalamic invasion for postoperative diabetes insipidus as well as higher perceived levels of distress after surgery, which may be established in larger patient cohorts. Furthermore, a subfrontal surgical approach seems to be predicted by tumors with hypothalamic invasion. In this case, preoperative magnetic resonance imaging grading may help guide the planning of an optimal surgical strategy for adults with craniopharyngioma to reduce postoperative morbidity.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

Vitex agnus castus effects on hyperprolactinaemia.

Background: Vitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome. Methods: We have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia. Results: Some evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure. Conclusion: It appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it.

Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon.

Hypothalamic obesity (HO) is a complex and rare disorder affecting multiple regulatory pathways of energy intake and expenditure in the brain as well as the regulation of the autonomic nervous system and peripheral hormonal signaling. It can be related to monogenic obesity syndromes which often affect the central leptin-melanocortin pathways or due to injury of the hypothalamus from pituitary and hypothalamic tumors, such as craniopharyngioma, surgery, trauma, or radiation to the hypothalamus. Traditional treatments of obesity, such as lifestyle intervention and specific diets, are still a therapeutic cornerstone, but often fail to result in meaningful and sustained reduction of body mass index. This review will give an update on pharmacotherapies of HO related to hypothalamic injury. Recent obesity drug developments are promising for successful obesity intervention outcomes.

Tocilizumab for the fifth progression of cystic childhood craniopharyngioma-a case report.

We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local radiotherapy. She had severe visual impairment, panhypopituitarism including diabetes insipidus, and several components of hypothalamic damage, including morbid obesity and severe fatigue. To prevent further late effects hampering her quality of survival, she was treated biweekly with intravenous tocilizumab, an anti-interleukin-6 agent, which stabilized the cyst for a prolonged time. Based on the biology of adamantinomatous craniopharyngioma, this immune-modulating treatment seems promising for the treatment of this cystic tumor in order to reduce surgery and delay or omit radiotherapy.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

A pharmacophore screening approach of homeopathic phenols for a renovated design of fragment-optimized Bauhiniastatin-1 as a drug against acromegaly.

OBJECTIVE: Acromegaly is a fatal and chronic disease that is caused by the abnormal secretion of growth hormone (GH) by the pituitary adenoma or pituitary tumor, resulting in an increased circulated concentration of insulin-like growth factors 1 (IGF-1), where in most of the cases it is secreted by a pituitary tumor. Higher levels of GH cause an increase in IGF-1 in the liver leading to multiple conditions such as cardiovascular diseases, glucose imbalance, cancer, and sleep apnea. Medical treatments such as surgery and radiotherapy can be used as the first choice of patients; however, specified human growth hormone control should be an essential treatment strategy due to an incidence rate of 0.2-1.1 yearly. Therefore, the main focus of this study is to develop a novel drug for treating acromegaly by exploiting medicinal plants that have been screened using phenol as a pharmacophore model to identify target therapeutic medicinal plant phenols. MATERIALS AND METHODS: The screening identified thirty-four pharmacophore matches of medicinal plant phenols. These were selected as suitable ligands and were docked against the growth hormone receptor to calculate their binding affinity. The candidate with the highest screened score was fragment-optimized and subjected to absorption, distribution, metabolism, and excretion (ADME) analysis, in-depth toxicity predictions, interpretation of Lipinski's rule, and molecular dynamic simulations to check the behavior of the growth hormone with the fragment-optimized candidate. RESULTS: The highest docking energy was calculated as -6.5 K/mol for Bauhiniastatin-1. Enhancing the performance of Bauhiniastatin-1 against the growth hormone receptor with fragment optimization portrayed that human growth hormone inhibition can be executed in a more efficient and better way. Fragment-optimized Bauhiniastatin-1 (FOB) was predicted with high gastrointestinal absorption, a water solubility of -2.61 as soluble, and synthetic accessibility of 4.50, achieving Lipinski's rule of 5, with low organ toxicity prediction and interpreting a positive behavior against the targeted protein. The discovery of a de novo drug candidate was confirmed by the docking of fragment-optimized Bauhiniastatin-1 (FOB), which had an energy of -4,070 Kcal/mol. CONCLUSIONS: Although successful and completely harmless, present healthcare treatment does not always eradicate the disease in some individuals. Therefore, novel formulas or combinations of currently marketed medications and emergent phytochemicals will provide new possibilities for these instances.

The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas-New Potential Therapeutic Approach-A Systematic Review.

Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012-2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.

Dopamine agonists for the treatment of pituitary tumours: From ergot extracts to next generation therapies.

Dopamine agonists are a key tool in the therapeutic arsenal of endocrinologists worldwide. They exert their effects by binding to dopamine-2 (D2) receptors expressed by pituitary tumour cells to modulate hormonal secretion and tumour size. They are the established first-line treatment for prolactinomas which express high levels of D2 receptors. Growing data support their use as an adjuvant treatment option for other pituitary tumours including growth hormone, adrenocorticotrophic hormones, thyroid hormone secreting adenomas and nonfunctional pituitary tumours, all of which have been shown to express D2 receptors as well, albeit to varying extents. For those pituitary tumours inadequately treated by dopamine agonist alone, combined agonism of D2 and somatostatin receptors represent a new frontier in clinical development. Here we review the development and role of dopamine agonist for the treatment of prolactinomas, the literature supporting their adjuvant use for the treatment of all other pituitary tumours, and recent progress in the development of the next generation of chimeric compounds that target D2 and other receptor subtypes highly expressed on pituitary tumour cells.

Pituitary Stalk Stretch Predicts Postoperative Diabetes Insipidus After Pituitary Macroadenoma Transsphenoidal Resection.

BACKGROUND: Manipulation of the pituitary stalk, posterior pituitary gland, and hypothalamus during transsphenoidal pituitary adenoma resection can cause disruption of water electrolyte regulation leading to diabetes insipidus (DI). OBJECTIVE: To determine whether pituitary stalk stretch is an independent risk factor for postoperative DI after pituitary adenoma resection. METHODS: A retrospective review was performed of patients undergoing endoscopic endonasal resection of pituitary macroadenoma between July 2010 and December 2016 by a single neurosurgeon. We analyzed preoperative and postoperative imaging metrics to assess predictors for postoperative DI. RESULTS: Of the 234 patients undergoing resection, 41 (17.5%) developed postoperative DI. DI was permanent in 10 (4.3%) and transient in 31 (13.2%). The pituitary stalk stretch, measured as the change in stalk length from preoperative to postoperative imaging, was greater in the DI compared with the non-DI group (10.1 mm vs 5.9 mm, P < .0001). The pituitary stalk stretch was associated with DI with significant difference in mean pituitary stalk stretch between non-DI group vs DI group (5.9 mm vs 10.1 mm, P < .0001). Multivariate analysis revealed that pituitary stalk stretch >10 mm was a significant independent predictor of postoperative DI [odds ratios = 2.56 (1.10-5.96), P = .029]. When stratified into transient and permanent DI, multivariable analysis showed that pituitary stalk stretch >10 mm was a significant independent predictor of transient DI [odds ratios = 2.71 (1.0-7.1), P = .046] but not permanent DI. CONCLUSION: Postoperative pituitary stalk stretch after transsphenoidal pituitary adenoma surgery is an important factor for postoperative DI. We propose a reconstruction strategy to mitigate stalk stretch.

Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

Effects of Imatinib Combined With Everolimus on Mouse Pituitary Tumor Cell AtT-20.

Context: Pituitary adenoma is a clinical syndrome in which excessive production of pituitary corticotropin (ACTH). For ACTH tumor cells, researchers know little about the influence of the cell-cycle process on ACTH production and cell proliferation. Some research has shown that imatinib can induce apoptosis of tumor cells. Objective: The study intended to explore the effects and molecular mechanisms of imatinib combined with everolimus on AtT-20 cells in AtT-20 mouse pituitary tumors. Design: The research team performed a laboratory study using murine corticotropin tumor AtT-20 cells. Setting: The study took place at the Department of Neurosurgery at Renmin Hospital of the Hubei University of Medicine in Shiyan, Hubei, China. Intervention: The research team cultured the cells in AtT-20-cell-specific medium containing 100 µg/mL of streptomycin, 100 U/mL of penicillin, and 10% fetal bovine serum at 37°C and 5% CO2. The team divided the cells into a control group, a normal culture without the drug, and an intervention group, incubated for 24 hours with 1 µM of imatinib and 3 µM of everolimus when the cells grew to 40% confluence. Outcome Measures: The research team: (1) determined the effects of the combined drugs on cell viability using a methyl thiazolyl tetrazolium (MTT) assay; (2) detected the cell's mitochondrial membrane potential and LDH leakage using "sytox blue, 5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide," CBIC2(3) or JC-1, and lactate dehydrogenase (LDH) assay kits, respectively; (3) detected AtT-20 cell apoptosis using a "terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling" (TUNEL) kit; (4) analyzed the expression of protein kinase B (p-Akt), cAMP-response element binding protein (p-CREB), p27, p53, and cyclin E using a Western blot test; (5) detected the mRNA expression of opioid melanin procorticotropin (POMC)), caspase-3, and pituitary tumor transforming gene 1 (PTTG1) using reverse transcription-polymerase chain reaction (RT-PCR); (6) measure the concentration of adreno-cortico-tropic-hormone (ACTH) in the supernatant using an enzyme-linked immunoassay (ELISA) kit; and (7) assessed the cell cycle distribution using flow cytometry. Results: No differences existed in cell viability between the groups at the baseline (0 h) of the culture period (P > .05). Compared to the control group, the intervention group's: (1) cell viability was significantly lower at 4, 8, and 12 hours and postintervention at 16 hours (P < .001); (2) LDH concentration was significantly higher (P < .001); (3) mitochondrial membrane potential was significantly lower (P < .001); (4) apoptosis rate of TUNEL was significantly higher (P < .001 ); (5) expression of p-Akt, p-CREB phosphorylation, and cyclin E was significantly lower (P < .001), (6) expression of p27 and p53 protein was significantly higher (P < .001); (7) mRNA expression of POMC and PTTG1 were significantly lower (P < .001); (8) mRNA expression of caspase-3 was significantly higher (P < .001); (9) concentration of ACTH was lower (P < .001); and (10) percentage of cells in the G0/G1 phase was significantly higher, while the percentage of cells in the S phase was significantly lower (P < .05). Conclusions: Imatinib combined with everolimus can affect the AtT-20 cell cycle through the signaling pathway of the phosphatidylin-ositol-3-kinase (PI3K)/Akt/ protein kinase A (PKA) system and can inhibit cell proliferation and induce cell apoptosis. Therefore, Imatinib and everolimus may be an effective combination of candidates for drugs for mouse pituitary tumor.

Expanded endoscopic endonasal approach for the resection of midline craniopharyngiomas with hypothalamic involvement.

BACKGROUND: With relevant surrounding neurological structures and potential involvement of the hypothalamus, the surgical management of craniopharyngiomas is complex. Compared to the transcranial approach, the expanded endoscopic endonasal approach provides direct access to the supradiaphragmatic and retrochiasmatic areas without crossing nerves and arteries. METHOD: Based on our substantial experience of 68 patients operated on between 2008 and 2022 by endoscopic surgery, our strategy has evolved such that all of our midline infundibular craniopharyngiomas with hypothalamic involvement are currently treated with an expanded endonasal route, except for tumours isolated to the third ventricle. Vascularized mucosal nasoseptal flaps are required for closure. Fine details of the related anatomy and surgical technique are described. CONCLUSION: Expanded endoscopic endonasal approach is a safe and effective route for resection of midline suprasellar craniopharyngiomas with hypothalamic involvement in centres of expertise.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.