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Oncology Research 2024Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in (α subunit of stimulatory G protein). Mutations in...
Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in (α subunit of stimulatory G protein). Mutations in are associated with clinical features of smaller and less invasive tumors. However, the role of mutations in the invasiveness of GHPAs is unclear. mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 () was evaluated with RT-qPCR. was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated compared with that in mice with wild-type . Consistently, the invasiveness of mutant -expressing GH3 cells decreased. is uniquely expressed at high levels in GHPAs harboring mutated . Accordingly, upregulation inhibited tumor cell invasion, and conversely, downregulation increased tumor cell invasion. Mechanistically, mutations inhibit EMT in GHPAs. in mutated cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated . Our data suggest that mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the signaling pathway.
Topics: GTP-Binding Protein alpha Subunits, Gs; Animals; Humans; Growth Hormone-Secreting Pituitary Adenoma; Mice; Mutation; Chromogranins; Neoplasm Invasiveness; Epithelial-Mesenchymal Transition; RNA, Long Noncoding; Female; Male; Cell Line, Tumor; Adenoma; Middle Aged; Adult; Cell Proliferation; Xenograft Model Antitumor Assays; Wnt Signaling Pathway; Gene Expression Regulation, Neoplastic
PubMed: 38827318
DOI: 10.32604/or.2024.046007 -
Brain Research Bulletin Aug 2024Subiculum is a pivotal output component of the hippocampal formation, a structure often overlooked in neuroscientific research. Here, this review aims to explore the... (Review)
Review
Subiculum is a pivotal output component of the hippocampal formation, a structure often overlooked in neuroscientific research. Here, this review aims to explore the role of the subiculum in various brain disorders, shedding light on its significance within the functional-neuroanatomical perspective on neurological diseases. The subiculum's involvement in multiple brain disorders was thoroughly examined. In Alzheimer's disease, subiculum alterations precede cognitive decline, while in epilepsy, the subiculum plays a critical role in seizure initiation. Stress involves the subiculum's impact on the hypothalamic-pituitary-adrenocortical axis. Moreover, the subiculum exhibits structural and functional changes in anxiety, schizophrenia, and Parkinson's disease, contributing to cognitive deficits. Bipolar disorder is linked to subiculum structural abnormalities, while autism spectrum disorder reveals an alteration of inward deformation in the subiculum. Lastly, frontotemporal dementia shows volumetric differences in the subiculum, emphasizing its contribution to the disorder's complexity. Taken together, this review consolidates existing knowledge on the subiculum's role in brain disorders, and may facilitate future research, diagnostic strategies, and therapeutic interventions for various neurological conditions.
Topics: Humans; Hippocampus; Brain Diseases; Alzheimer Disease
PubMed: 38825254
DOI: 10.1016/j.brainresbull.2024.110993 -
Genome Medicine May 2024Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant...
BACKGROUND
Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS).
METHODS
The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations.
RESULTS
Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features.
CONCLUSIONS
The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.
Topics: Hypopituitarism; Animals; Humans; Pituitary Gland; Mice, Knockout; Mice; Phenotype; Female; Male; Disease Models, Animal; Exome Sequencing; Septo-Optic Dysplasia
PubMed: 38822427
DOI: 10.1186/s13073-024-01347-y -
World Journal of Surgical Oncology Jun 2024Delayed epistaxis after endoscopic transnasal pituitary tumor resection (ETPTR) is a critical complication, tending to cause aspiration or hemorrhagic shock. This study...
BACKGROUND
Delayed epistaxis after endoscopic transnasal pituitary tumor resection (ETPTR) is a critical complication, tending to cause aspiration or hemorrhagic shock. This study assessed clinical characteristics, risk factors, and provide treatment and prevention advice of this complication.
METHODS
This was a retrospective monocentric analysis of 862 patients who underwent ETPTR. Statistical analyses of clinical data revealed the incidence, sources and onset time of delayed epistaxis. Univariate analysis and binary logistic regression were used to identify risk factors.
RESULTS
The incidence of delayed epistaxis was 2.78% (24/862), with an average onset time of 20.71 ± 7.39 days. The bleeding sources were: posterior nasal septal artery branch of sphenopalatine artery (12/24), multiple inflammatory mucosae (8/24), sphenopalatine artery trunk (3/24) and sphenoid sinus bone (1/24). Univariate analysis and binary logistic regression analysis confirmed that hypertension, nasal septum deviation, chronic rhinosinusitis and growth hormone pituitary tumor subtype were independent risk factors for delayed epistaxis. Sex, age, history of diabetes, tumor size, tumor invasion and operation time were not associated with delayed epistaxis. All patients with delayed epistaxis were successfully managed through endoscopic transnasal hemostasis without recurrence.
CONCLUSIONS
Delayed epistaxis after ETPTR tends to have specific onset periods and risk factors. Prevention of these characteristics may reduce the occurrence of delayed epistaxis. Endoscopic transnasal hemostasis is recommended as the preferred treatment for delayed epistaxis.
Topics: Humans; Epistaxis; Male; Female; Retrospective Studies; Middle Aged; Pituitary Neoplasms; Risk Factors; Adult; Aged; Follow-Up Studies; Prognosis; Incidence; Endoscopy; Postoperative Complications; Young Adult; Time Factors; Adolescent; Natural Orifice Endoscopic Surgery
PubMed: 38822349
DOI: 10.1186/s12957-024-03428-z -
Scientific Reports May 2024To construct a prediction model of olfactory dysfunction after transnasal sellar pituitary tumor resection based on machine learning algorithms. A cross-sectional study...
To construct a prediction model of olfactory dysfunction after transnasal sellar pituitary tumor resection based on machine learning algorithms. A cross-sectional study was conducted. From January to December 2022, 158 patients underwent transnasal sellar pituitary tumor resection in three tertiary hospitals in Sichuan Province were selected as the research objects. The olfactory status was evaluated one week after surgery. They were randomly divided into a training set and a test set according to the ratio of 8:2. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. Based on different machine learning algorithms, BP neural network, logistic regression, decision tree, support vector machine, random forest, LightGBM, XGBoost, and AdaBoost were established to construct olfactory dysfunction risk prediction models. The accuracy, precision, recall, F1 score, and area under the ROC curve (AUC) were used to evaluate the model's prediction performance, the optimal prediction model algorithm was selected, and the model was verified in the test set of patients. Of the 158 patients, 116 (73.42%) had postoperative olfactory dysfunction. After missing value processing and feature screening, an essential order of influencing factors of olfactory dysfunction was obtained. Among them, the duration of operation, gender, type of pituitary tumor, pituitary tumor apoplexy, nasal adhesion, age, cerebrospinal fluid leakage, blood scar formation, and smoking history became the risk factors of olfactory dysfunction, which were the key indicators of the construction of the model. Among them, the random forest model had the highest AUC of 0.846, and the accuracy, precision, recall, and F1 score were 0.750, 0.870, 0.947, and 0.833, respectively. Compared with the BP neural network, logistic regression, decision tree, support vector machine, LightGBM, XGBoost, and AdaBoost, the random forest model has more advantages in predicting olfactory dysfunction in patients after transnasal sellar pituitary tumor resection, which is helpful for early identification and intervention of high-risk clinical population, and has good clinical application prospects.
Topics: Humans; Pituitary Neoplasms; Male; Female; Olfaction Disorders; Machine Learning; Middle Aged; Adult; Cross-Sectional Studies; Postoperative Complications; Risk Factors; ROC Curve; Risk Assessment; Aged; Algorithms
PubMed: 38822064
DOI: 10.1038/s41598-024-62963-7 -
Cureus Apr 2024Hypophysitis is a rare pituitary gland disease primarily seen in females of reproductive age. Patients can present with various non-specific symptoms, which makes...
Hypophysitis is a rare pituitary gland disease primarily seen in females of reproductive age. Patients can present with various non-specific symptoms, which makes diagnosis challenging. Appropriate endocrine workup supplemented with magnetic resonance imaging (MRI) helps establish a diagnosis. We present a case of a 22-year-old postpartum female who came with nausea, vomiting, and abdominal pain. Global endocrine insufficiency was seen in the laboratory workup, and an MRI confirmed the diagnosis of hypophysitis. She was treated with steroid and thyroid hormone supplementation.
PubMed: 38817522
DOI: 10.7759/cureus.59396 -
Frontiers in Neuroscience 2024Pregnancy and the postpartum period induce physiological changes that can influence women's cognitive functions. Alzheimer's disease (AD) has a higher prevalence in...
Pregnancy and the postpartum period induce physiological changes that can influence women's cognitive functions. Alzheimer's disease (AD) has a higher prevalence in women and is exacerbated by early life stress. In the present study, we found that late adolescent social isolation combined with the experience of pregnancy and delivery accelerates the onset of cognitive deficits in 5xFAD dams, particularly affecting their ability to recognize novelty. These cognitive deficits manifested as early as 16 weeks, earlier than the usual timeline for these mice, and were closely associated with increased levels of corticosterone, suggesting dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Notably, the presence of -amyloid plaques in brain regions associated with novelty recognition did not significantly contribute to these deficits. This highlights the potential role of stress and HPA axis dysregulation in the development of cognitive impairments related to AD, and underscores the need for further investigation.
PubMed: 38812977
DOI: 10.3389/fnins.2024.1366199 -
TouchREVIEWS in Endocrinology Apr 2024Pituitary infiltration by systemic lymphoma is an exceedingly rare occurrence. Given its high mortality rate, it is crucial to recognize its clinical, biochemical and...
Pituitary infiltration by systemic lymphoma is an exceedingly rare occurrence. Given its high mortality rate, it is crucial to recognize its clinical, biochemical and radiological features in order to provide timely intervention. We present the case of a 26-year-old male with a history of human immunodeficiency virus (HIV) infection who presented to the hospital with severe anemia, persistent fever, weight loss and diarrhea over the previous 4 months. Physical examination revealed a compromised general condition, fever, pallor, hepatomegaly and lymphadenopathy. Cervical lymph node biopsy confirmed Burkitt lymphoma (BL). During hospitalization, the patient developed polyuria, polydipsia, hypernatremia, fluid-resistant hypotension and hypoglycaemia. Corticosteroid therapy was initiated due to suspected adrenal insufficiency, resulting in clinical improvement but exacerbation of polyuria and hypernatremia. Plasma and urinary osmolarity confirmed arginine vasopressin deficiency, and assessment of anterior pituitary reserve revealed hypopituitarism, necessitating hormonal replacement therapy. Sellar magnetic resonance imaging with contrast revealed pituitary infiltration. The patient subsequently developed septic shock and died. BL accounts for approximately 10% of the cases of pituitary infiltration associated with lymphoma. Clinical presentation is heterogeneous, with panhypopituitarism often serving as the initial manifestation. Sellar magnetic resonance imaging plays a pivotal role in the differential diagnosis. Management typically entails chemotherapy, immunotherapy, radiation and hormonal replacement therapy. This case report describes a patient with BL and HIV infection who developed panhypopituitarism due to pituitary infiltration, an exceedingly rare presentation considered a medical emergency.
PubMed: 38812670
DOI: 10.17925/EE.2024.20.1.11 -
TouchREVIEWS in Endocrinology Apr 2024The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with... (Review)
Review
The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide.
PubMed: 38812667
DOI: 10.17925/EE.2024.20.1.9