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Xiang Y, Wu Y, Liu H, Chen Z, Pan J. Association of coagulation-related indicators with postoperative venous thromboembolism occurrence in patients with pituitary tumors. Sci Rep 2025; 15:16694. [PMID: 40368990 PMCID: PMC12078525 DOI: 10.1038/s41598-025-01029-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 05/02/2025] [Indexed: 05/16/2025] Open
Abstract
This study aimed to analyze risk factors for postoperative VTE in pituitary tumor resection patients, focusing on coagulation indicators and their predictive value. This study collected clinical data from 300 patients who underwent pituitary adenoma resection from January 2021 to August 2023 in the Department of Neurosurgery, the Second Clinical College of the Army Medical University, China. Logistic regression modeling was used to identify risk factors for VTE. Restricted cubic spline curves were used to characterize the dose-response relationship between coagulation-related indicators and the risk of venous thromboembolism. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve to evaluate the predictive power of coagulation-related indicators. Multivariate analysis showed that D-dimer, platelet count and hemoglobin (Hb) were significant predictors of VTE with OR (95% CI) of 1.967 (1.441-2.808), 1.020 (1.013-1.029), and 0.952 (0.914-0.994), respectively. The AUCs for D-dimer, Platelet Count, and Hb were 0.708, 0.731, and 0.712, respectively. The AUC for combining the three coagulation indices was the largest, 0.838. The combined use of D-dimer, Hb, and platelet count can identify high-risk patients early, enabling timely implementation of antithrombotic strategies.
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Affiliation(s)
- Yi Xiang
- Chongqing General Hospital, Chongqing University, 118 Star Avenue, Liangjiang New Area, Chongqing, China
| | - Ya Wu
- The Second Clinical College of the Army Medical University, Chongqing, China
| | - Huan Liu
- The Second Clinical College of the Army Medical University, Chongqing, China
| | - Zheng Chen
- The Second Clinical College of the Army Medical University, Chongqing, China
| | - JinYu Pan
- Chongqing General Hospital, Chongqing University, 118 Star Avenue, Liangjiang New Area, Chongqing, China.
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Liu J, Ye Z, Zhang Y, Su W, Liu J, Chen T, Shi Y, Liu L, Lu J, Cai Z, Zhong Q, Wang P, Pu J, Liu J, Wei Y, Pan H, Zhu H, Deng K, Wang R, Lu L, Hu X, Yao Y. Exploring the gut microbiome and serum metabolome interplay in non-functioning pituitary neuroendocrine tumors. Front Microbiol 2025; 16:1541683. [PMID: 40236482 PMCID: PMC11997625 DOI: 10.3389/fmicb.2025.1541683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 02/12/2025] [Indexed: 04/17/2025] Open
Abstract
The gut microbiome has emerged as a potential factor in cancer pathogenesis, but its role in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) remains unclear. This study aimed to elucidate gut microbiome and metabolomic alterations in NF-PitNETs by comparing microbial diversity, pathogenic bacteria, and serum metabolomic profiles between NF-PitNET patients and healthy controls. The gut microbiome was assessed through 16S rRNA sequencing, while serum metabolomics was analyzed using mass spectrometry. Correlation analyses identified potential links between microbial characteristics and metabolic markers. The results revealed that specific pathogenic bacteria, such as Bacteroides, were significantly enriched in NF-PitNET patients. Multi-omics correlations suggested that altered microbiota might contribute to NF-PitNET pathogenesis by modulating host metabolic pathways. These findings highlight the potential role of gut microbiome dysbiosis and its metabolic effects in NF-PitNET development, offering insights into possible therapeutic and diagnostic targets.
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Affiliation(s)
- Jifang Liu
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhang Ye
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Zhang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wan Su
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Liu
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tianqi Chen
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanan Shi
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lulu Liu
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiao Lu
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zian Cai
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qing Zhong
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pei Wang
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Pu
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jinghua Liu
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuchen Wei
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Pan
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huijuan Zhu
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Renzhi Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
| | - Lin Lu
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaomin Hu
- State Key Laboratory for Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Yao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pituitary Disease Innovative Diagnosis and Treatment Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Khalil I, Hossain MI. Treatment-resistant Cushing disease and acromegaly in a young woman: A case of functional pituitary macroadenoma. Radiol Case Rep 2025; 20:2013-2019. [PMID: 39926265 PMCID: PMC11802362 DOI: 10.1016/j.radcr.2025.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 12/09/2024] [Accepted: 01/03/2025] [Indexed: 02/11/2025] Open
Abstract
Cushing disease and acromegaly are common endocrine disorders caused by excessive cortisol and growth hormone production, respectively. Both conditions can co-occur due to functioning pituitary adenomas, which are typically benign pituitary gland tumors. This report discusses a 30-year-old woman with hyperpituitarism leading to treatment-resistant Cushing disease and acromegaly caused by a functional pituitary macroadenoma. A 30-year-old woman presented with a history of excessive weight gain, facial puffiness, fatigue, persistent headaches, and visual disturbances. Clinical examination revealed features consistent with Cushing disease and acromegaly, including a moon face, central obesity, and large hands and feet-the ophthalmologic evaluation identified bitemporal hemianopia, suggesting optic chiasm compression. Laboratory results showed elevated ACTH, IGF-1, and prolactin levels, alongside confirmed hypercortisolism. The patient also had secondary diabetes mellitus and galactorrhea-initial treatment with octreotide provided limited benefit, with persistent hormone elevations and insufficient symptom control. The patient underwent endonasal endoscopic transsphenoidal resection of the pituitary macroadenoma, leading to marked symptomatic and hormonal improvements. This underscores the diagnostic challenge and treatment complexity of such cases. Early diagnosis is critical for optimizing outcomes in patients with hyperpituitarism and mitigating complications. This case highlights the importance of multidisciplinary management and the necessity of long-term follow-up to monitor for recurrence and ensure sustained remission.
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Cole KL, Rennert RC, Rawanduzy CA, Brandel MG, Findlay MC, Azab MA, Karsy M, Couldwell WT. Cost outcomes of pituitary adenoma resection: The use of a hybrid microscopic/endoscopic surgery. Surg Neurol Int 2025; 16:50. [PMID: 40041046 PMCID: PMC11878703 DOI: 10.25259/sni_1043_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 01/17/2025] [Indexed: 03/06/2025] Open
Abstract
Background The pathogenesis, surgical techniques, and outcomes of pituitary adenomas (PAs) remain variable. We compared our surgical techniques and perioperative/long-term PA outcomes to highlight the hybrid microscopic/endoscopic technique used to optimize efficiency, cost savings, and outcomes in PA surgery. Methods Consecutive PA cases performed from January 2017 through February 2020 were evaluated retrospectively. A cost analysis by surgical approach was performed combining this primarily microscopic series, with endoscopic visual assist, and a separate cohort of consecutive intra-institutional endoscopic-only PA resections. Results Among 160 patients included in the main cohort analysis (mean age 51.5 ± 16.2; 89 females [55.6%]), a microscope was used in 81.9% of cases, with endoscopic assistance (hybrid) or the endoscope alone used in the remaining cases. Surgical complications occurred in 5 cases (3.1%): postoperative diabetes insipidus in 3 (1.9%), electrolyte imbalances requiring additional drug treatment in 3 (1.9%), and syndrome of inappropriate anti-diuretic hormone release in 2 (1.2%). Thirty-three additional patients were included in the cost analysis (193 total). Patients treated with a microscopic-only approach had the lowest operating time (mean normalized operating room costs 1.00 [95% confidence interval (CI) 0.95, 1.04], P < 0.001; mean normalized total direct costs 5.00 [95%CI 4.69, 5.31], P = 0.008), with hybrid and endoscopic-only approaches having higher comparable operating times and costs. Conclusion PA surgery using a primarily microscopic approach (with endoscopic assistance for complex cases) remains a safe, efficient, and cost-effective strategy and results in shorter anesthesia time to reduce patient complications while maintaining excellent endocrinologic outcomes. Keywords Endoscope, Hybrid approach, Microscope, Pituitary adenoma, Transnasal surgery, Transsphenoidal surgery.
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Affiliation(s)
- Kyril L. Cole
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States
| | - Robert C. Rennert
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States
| | | | - Michael G. Brandel
- Department of Neurological Surgery, University of California San Diego, La Jolla, United States
| | - Matthew C. Findlay
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States
| | - Mohammed A. Azab
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States
| | - Michael Karsy
- Department of Neurosurgery, University of Michigan, Ann Arbor, United States
| | - William T. Couldwell
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States
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Wang L, Liu S, Zheng J, Li R, Xing Z. Contributing factors to postoperative surgical site infections in pituitary neuroendocrine tumors undergoing endonasal transsphenoidal resection. Sci Rep 2025; 15:2995. [PMID: 39848981 PMCID: PMC11757733 DOI: 10.1038/s41598-025-86567-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 01/13/2025] [Indexed: 01/25/2025] Open
Abstract
Pituitary Neuroendocrine Tumors (PitNETs), often treated via endonasal transsphenoidal resection, present a risk for postoperative surgical site infections (SSIs), including intracranial infections such as meningitis. Identifying the risk factors associated with these infections is crucial for improving surgical outcomes and patient care. A retrospective study was conducted at a medical center from June 2020 to June 2023. The study included 20 patients with postoperative intracranial infections and 50 controls without infections. Inclusion criteria involved adult patients diagnosed with PitNETs who underwent standard endonasal transsphenoidal surgery and provided informed consent. Exclusion criteria included previous neurosurgical procedures, preoperative infections, concurrent severe diseases, or alternative surgical approaches. Diagnostic criteria for intracranial infections were based on clinical, hematological, cerebrospinal fluid, radiological, and microbiological findings. Statistical analyses were performed using IBM SPSS, focusing on univariate and multivariate logistic regression analyses. Univariate analysis showed no significant association of intracranial infections with factors like smoking history, previous craniotomy, operation time, hypertension, preoperative sphenoid sinusitis, BMI, and age. However, postoperative CSF leaks, intracranial pneumocephalus, diabetes mellitus, and tumor extension to the third ventricle were significantly associated with infections. Multivariate logistic regression further confirmed these findings, with significant odds ratios for these factors. The study reveals a significant correlation between postoperative CSF leaks, intracranial pneumocephalus, diabetes mellitus, and tumor extension to the third ventricle with the occurrence of SSIs following endonasal transsphenoidal resection of PitNETs. Microbial analysis revealed Escherichia coli as the most prevalent pathogen in post-surgery infections, with notable antibiotic resistance patterns observed in key bacteria, necessitating careful antibiotic selection. Tailored clinical treatment strategies addressing these risk factors are essential to reduce the incidence of postoperative SSIs and enhance patient safety.
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Affiliation(s)
- Lei Wang
- Department of Neurosurgery, Xinxiang Central Hospital, 56 Jinsui Avenue, Weibin District, Xinxiang, 453000, Henan, China
| | - Shanxian Liu
- Department of Neurosurgery, Xinxiang Central Hospital, 56 Jinsui Avenue, Weibin District, Xinxiang, 453000, Henan, China
| | - Jie Zheng
- Department of Neurosurgery, Xinxiang Central Hospital, 56 Jinsui Avenue, Weibin District, Xinxiang, 453000, Henan, China
| | - Rui Li
- Department of Neurosurgery, Xinxiang Central Hospital, 56 Jinsui Avenue, Weibin District, Xinxiang, 453000, Henan, China
| | - Zhenyi Xing
- Department of Neurosurgery, Xinxiang Central Hospital, 56 Jinsui Avenue, Weibin District, Xinxiang, 453000, Henan, China.
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Yang Q, Ke T, Wu J, Wang Y, Li J, He Y, Yang J, Xu N, Yang B. Preoperative prediction of pituitary neuroendocrine tumor invasion using multiparametric MRI radiomics. Front Oncol 2025; 14:1475950. [PMID: 39850814 PMCID: PMC11754205 DOI: 10.3389/fonc.2024.1475950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Accepted: 12/03/2024] [Indexed: 01/25/2025] Open
Abstract
Objective The invasiveness of pituitary neuroendocrine tumor is an important basis for formulating individualized treatment plans and improving the prognosis of patients. Radiomics can predict invasiveness preoperatively. To investigate the value of multiparameter magnetic resonance imaging (mpMRI) radiomics in predicting pituitary neuroendocrine tumor invasion into the cavernous sinus (CS) before surgery. Patients and methods The clinical data of 133 patients with pituitary neuroendocrine tumor (62 invasive and 71 non-invasive) confirmed by surgery and pathology who underwent preoperative mpMRI examination were retrospectively analyzed. Data were divided into training set and testing set according to different field strength equipment. Radiomics features were extracted from the manually delineated regions of interest in T1WI, T2WI and CE-T1, and the best radiomics features were screened by LASSO algorithm. Single radiomics model (T1WI, T2WI, CE-T1) and combined radiomics model (T1WI+T2WI+CE-T1) were constructed respectively. In addition, clinical features were screened to establish clinical model. Finally, the prediction model was evaluated by ROC curve, calibration curve and decision curve analysis (DCA). Results A total of 10 radiomics features were selected from 306 primitive features. The combined radiomics model had the highest prediction efficiency. The area under curve (AUC) of the training set was 0.885 (95% CI, 0.819-0.952), and the accuracy, sensitivity, and specificity were 0.951,0.826, and 0.725. The AUC of the testing set was 0.864 (95% CI, 0.744-0.985), and the accuracy, sensitivity, and specificity were 0.829,0.952, and 0.700. DCA showed that the combined radiomics model had higher clinical net benefit. Conclusion The combined radiomics model based on mpMRI can effectively and accurately predict the invasiveness of pituitary neuroendocrine tumor to CS preoperatively, and provide decision-making basis for clinical individualized treatment.
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Affiliation(s)
- Qiuyuan Yang
- Department of Medical Imaging, The Second People’s Hospital of Dali Prefecture, Dali, China
| | - Tengfei Ke
- Department of Medical Imaging, Yunnan Cancer Hospital, Kunming, China
| | - Jialei Wu
- Medical Imaging Center, The First Hospital of Kunming, Kunming, China
| | - Yubo Wang
- Medical Imaging Center, The First Hospital of Kunming, Kunming, China
| | - Jiageng Li
- Medical Imaging Center, The First Hospital of Kunming, Kunming, China
| | - Yimin He
- Department of Medical Imaging, The Second People’s Hospital of Dali Prefecture, Dali, China
| | - Jianxian Yang
- Department of Medical Imaging, The Second People’s Hospital of Dali Prefecture, Dali, China
| | - Nan Xu
- Department of Radiology, Air Force Medical Center, Air Force Medical University, Beijing, China
| | - Bin Yang
- Medical Imaging Center, The First Hospital of Kunming, Kunming, China
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Shen A, Min Y, Zhou D, Dai L, Lyu L, Zhan W, Jiang S, Zhou P. Adaptive evaluation of gross total resection rates for endoscopic endonasal approach based on preoperative MRI morphological features of pituitary adenomas. Front Oncol 2024; 14:1481899. [PMID: 39741971 PMCID: PMC11685135 DOI: 10.3389/fonc.2024.1481899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 12/02/2024] [Indexed: 01/03/2025] Open
Abstract
Objective This study aims to define a set of related anatomical landmarks based on preoperative Magnetic Resonance Imaging (MRI) of patients with pituitary adenomas (PAs). It explores the impact of the dynamic relationships between different anatomical landmarks and the tumor on the resection rate and tumor progression/recurrence during the endoscopic endonasal approach (EEA). Methods A single-center institutional database review was conducted, identifying patients with PAs treated with EEA from December 2018 to January 2023. Clinical data were reviewed, and anatomical landmarks were categorized into two regions: the suprasellar region and the cavernous sinus region. Following basic statistical and univariate logistic regression analyses, patients were randomly divided into training and validation sets. A nomogram was then established through the integration of least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis. The clinical prediction model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis. Kaplan-Meier curves were plotted for survival analysis. Results A total of 626 patients with PAs were included in the study, with gross total resection (GTR) achieved in 570 cases (91.05%). Significant differences were observed in the distribution of age, Knosp grade, and tumor size between the GTR and near total resection (NTR) groups. LASSO regression identified 8 key anatomical landmarks. The resulting model demonstrated an AUC of 0.96 in both the training and validation sets. Calibration curves indicated a strong agreement between the nomogram model and actual observations. Survival analysis revealed that the extent of resection (EOR), age, Knosp grade, tumor size, and PAs extending beyond several anatomical landmarks identified were significantly associated with the progression or recurrence of PAs. Conclusion This study proposes a model for adaptively assessing the resection rate of PAs by delineating relevant anatomical landmarks. The model comprehensively considers instrument manipulation angles, surgical accessibility during EEA procedures, anatomical variations, and the displacement of related anatomical structures in pathological states. This approach can assist neurosurgeons in preoperative planning and developing personalized surgical strategies.
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Affiliation(s)
- Ao Shen
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Yue Min
- Department of Neurosurgery, West China Hospital/West China School of Nursing, Chengdu, Sichuan, China
| | - Dongjie Zhou
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Lirui Dai
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Liang Lyu
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Wenyi Zhan
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Shu Jiang
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Peizhi Zhou
- Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
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Lindberg F, Gabri A, Kristiansson H, Gubanski M, Höybye C, Olsson M, Förander P, Skyrman S, Lippitz B, Fletcher-Sandersjöö A, Bartek J. Long-term tumor control following repeat gamma-knife radiosurgery of growing pituitary adenomas: a population-based cohort study. Acta Neurochir (Wien) 2024; 166:494. [PMID: 39641851 PMCID: PMC11624231 DOI: 10.1007/s00701-024-06341-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 10/29/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Gamma Knife radiosurgery (GKRS) is a well-established treatment for residual or growing pituitary adenomas (PAs) post-partial resection. However, some PAs grow even after initial GKRS, for which the efficacy of repeat GKRS is unclear. The primary objective of this study was to determine long-term progression-free survival (PFS) following repeated GKRS in patients with PA. The secondary objective was to determine predictors of tumor progression in these patients. METHODS Single-center, population-based consecutive cohort study of patients with recurrent PAs treated with repeated GKRS due to tumor progression between 1999 and 2022 at the Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden. PFS and predictors of tumor growth were assessed. RESULTS 23 patients were included, with a median follow-up time of 6.3 years. The 5-year PFS rate was 57%, and the median duration from repeat GKRS to tumor progression was 2.6 years. Tumor growth after repeat GKRS occurred exclusively within the first three years post-treatment. Older age at the time of repeat GKRS was a significant predictor of continued tumor growth (OR 1.09, p = 0.036). CONCLUSION Repeat GKRS is a feasible treatment alternative for PAs that exhibit growth following initial GKRS.
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Affiliation(s)
- Felicia Lindberg
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
| | - Alexander Gabri
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
| | - Helena Kristiansson
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Michael Gubanski
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Charlotte Höybye
- Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Martin Olsson
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Petter Förander
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Simon Skyrman
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Bodo Lippitz
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
| | - Alexander Fletcher-Sandersjöö
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Jiri Bartek
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
- Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark
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Xu L, Lei Z, Wang Q, Jiang Q, Xing B, Li X, Guo X, Wang Z, Li S, Huang Y, Lei T. Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular Reactive Oxygen Species in Prolactin-Secreting Pituitary Adenoma. Antioxid Redox Signal 2024. [PMID: 39360800 DOI: 10.1089/ars.2024.0611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
Aims: Dopamine agonists (DAs) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. Results: Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to bromocriptine (BRC) both in vitro and in vivo. Mechanistically, we demonstrated that intracellular reactive oxygen species (ROS) function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NFE2-like bZIP transcription factor 2 (NRF2) expression, which regulates intracellular ROS levels, thereby enhancing cell viability and conferring DA resistance to pituitary adenoma (PA) cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. Conclusion and Innovation: We demonstrated that AR plays a crucial role in mediating DA resistance in PRL adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas. Antioxid. Redox Signal. 00, 000-000.
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Affiliation(s)
- Linpeng Xu
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Zhuowei Lei
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Department of Orthopedics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Quanji Wang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Qian Jiang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Biao Xing
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Xingbo Li
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Guo
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Zihan Wang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Sihan Li
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Yimin Huang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
| | - Ting Lei
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China
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10
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Yuan X, Zhu J, Su X, Tan H, Wang S, Zheng X, Ding Y, Li S. Pituitary hyperplasia secondary to primary hypothyroidism in adolescents: A medical case report and literature review. Clin Case Rep 2024; 12:e9541. [PMID: 39502127 PMCID: PMC11535441 DOI: 10.1002/ccr3.9541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 07/26/2024] [Accepted: 09/14/2024] [Indexed: 11/08/2024] Open
Abstract
Prompt and precise diagnosis of pituitary hyperplasia secondary to primary hypothyroidism (PHPH) is crucial to avoid unwarranted pituitary surgery and potential permanent impairment. Although PHPH may present similarly to pituitary adenoma, it is responsive to thyroxine therapy, underscoring the critical role of differential diagnosis in the treatment of adolescent patients.
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Affiliation(s)
- Xiangfeng Yuan
- Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefeiAnhuiChina
- Department of Endocrinology, Funan Hospital of Traditional Chinese MedicineFuyangAnhuiChina
| | - Jiangyu Zhu
- Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical CollegeBengbu Medical CollegeBengbuAnhuiChina
| | - Xiaoyu Su
- Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical CollegeBengbu Medical CollegeBengbuAnhuiChina
| | - Huiling Tan
- Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Siqi Wang
- Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Xueying Zheng
- Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Yu Ding
- Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Sumei Li
- Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefeiAnhuiChina
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11
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Peng J, Yuan L, Kang P, Jin S, Ma S, Zhou W, Jia G, Zhang C, Jia W. Comprehensive transcriptomic analysis identifies three distinct subtypes of pituitary adenomas: insights into tumor behavior, prognosis, and stem cell characteristics. J Transl Med 2024; 22:892. [PMID: 39363281 PMCID: PMC11448088 DOI: 10.1186/s12967-024-05702-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 09/23/2024] [Indexed: 10/05/2024] Open
Abstract
BACKGROUND Pituitary adenomas (PAs) are the second most common intracranial tumor. While current diagnostic practices rely primarily on histological testing, they often fail to capture the molecular complexities of pituitary adenomas, underscoring the need for a molecular-based classification to refine therapeutic strategies and prognostic assessments. This study aims to provide a molecularly unbiased classification of pituitary adenomas and explore their unique gene expression patterns and clinical features. METHODS We performed unsupervised hierarchical clustering of the gene expression profiles of 117 PA samples to identify three distinct molecular subtypes. Subsequently, we analyzed the compiled transcriptomic profiles of each individual subtype for pathway enrichment. We also validated the new classification with a validation set containing 158 PAs and 24 pituitary adenoma stem cells (PASCs). RESULTS Consensus clustering of transcriptomic data from 117 pituitary adenoma (PA) samples identified three distinct molecular subtypes, each showing unique gene expression patterns and associated biological processes: Group I is enriched in signaling pathways, such as the cAMP signaling pathway and the calcium signaling pathway. Group II is primarily related to metabolic processes, including nitrogen metabolism and arginine biosynthesis in cancer. Group III predominantly shows enrichment in immune responses and potential malignant transformation of the disease, especially through cancer-related pathways such as the JAK-STAT signaling pathway and the PI3K-Akt signaling pathway. The immune profiling revealed distinct patterns for each subtype: Group I had higher dendritic cells and fewer CD8+ T cells, Group II had more monocytes and macrophages, and Group III had elevated levels of T cells. Additionally, there were differences in clinical characteristics and prognosis among the subtypes, with Group III having a worse prognosis, despite the smaller tumor size compared to other groups. Notably, differences in PASCs correlated with the molecular subtypes, with Group III stem cells being enriched in tumorigenesis pathways, PI3K-Akt signaling pathway and Ras signaling pathway. CONCLUSION Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification.
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Affiliation(s)
- Jiayi Peng
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Linhao Yuan
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Peng Kang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shucheng Jin
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shunchang Ma
- China National Clinical Research Center for Neurological Diseases, Fengtai, Beijing, China
| | - Wenjianlong Zhou
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Guijun Jia
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Fengtai, Beijing, China
| | - Chuanbao Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
| | - Wang Jia
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
- China National Clinical Research Center for Neurological Diseases, Fengtai, Beijing, China.
- Beijing Neurosurgical Institute, Beijing, China.
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12
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Chiloiro S, Vicari A, Mongelli G, Costanza F, Giampietro A, Mattogno PP, Lauretti L, Olivi A, De Marinis L, Doglietto F, Bianchi A, Pontecorvi A. Effects of glucocorticoid replacement therapy in patients with pituitary disease: A new perspective for personalized replacement therapy. Rev Endocr Metab Disord 2024; 25:855-873. [PMID: 39168952 PMCID: PMC11470908 DOI: 10.1007/s11154-024-09898-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/29/2024] [Indexed: 08/23/2024]
Abstract
Secondary adrenal insufficiency (SAI) is an endocrine disorder due to impaired secretion of ACTH resulting from any disease affecting the pituitary gland. Glucocorticoid replacement therapy is mandatory to ensure patient survival, haemodynamic stability, and quality of life. In fact, a correct dose adjustement is mandatory due to the fact that inappropriately low doses expose patients to hypoadrenal crisis, while inappropriately high doses contribute to glucose metabolic and cardiovascular deterioration. This review analyses the current evidence from available publications on the epidemiology and aetiology of SAI and examines the association between glucocorticoid replacement therapy and glucometabolic and cardiovascular effects.
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Affiliation(s)
- Sabrina Chiloiro
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Alessandra Vicari
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy.
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
| | - Ginevra Mongelli
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Flavia Costanza
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Antonella Giampietro
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Pier Paolo Mattogno
- Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Department of Ageing, Neurosciences Head Neck, and Orthopedics Sciences, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
| | - Liverana Lauretti
- Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Department of Ageing, Neurosciences Head Neck, and Orthopedics Sciences, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
| | - Alessandro Olivi
- Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Department of Ageing, Neurosciences Head Neck, and Orthopedics Sciences, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
| | - Laura De Marinis
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy.
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
| | - Francesco Doglietto
- Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
- Department of Ageing, Neurosciences Head Neck, and Orthopedics Sciences, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy.
| | - Antonio Bianchi
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Alfredo Pontecorvi
- Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy
- Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
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13
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Li J, Song H, Chen T, Zhang S, Zhang C, Ma C, Zhang L, Wang T, Qian Y, Deng X. Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/β-Catenin Signaling Pathway. Neuroendocrinology 2024; 114:589-601. [PMID: 38565081 PMCID: PMC11152009 DOI: 10.1159/000538560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/25/2024] [Indexed: 04/04/2024]
Abstract
INTRODUCTION Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/β-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/β-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.
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Affiliation(s)
- Junjun Li
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hao Song
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
- Guangyuan Central Hospital, Guangyuan, China
| | - Ting Chen
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Sixi Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Chao Zhang
- Xiangyang First People’s Hospital, Xiangyang, China
| | - Chen Ma
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Lingye Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Tengfei Wang
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuan Qian
- The Clinical Medical Research Center for Obstetrics and Gynecology (Yunnan Joint Key Laboratory), Kunming City of Maternal and Child Health Hospital, Kunming City of Women and Children Hospital, Kunming, China
| | - Xingli Deng
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
- Puer People’s Hospital, Puer, China
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14
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Tang J, Mou M, Zheng X, Yan J, Pan Z, Zhang J, Li B, Yang Q, Wang Y, Zhang Y, Gao J, Li S, Yang H, Zhu F. Strategy for Identifying a Robust Metabolomic Signature Reveals the Altered Lipid Metabolism in Pituitary Adenoma. Anal Chem 2024; 96:4745-4755. [PMID: 38417094 DOI: 10.1021/acs.analchem.3c03796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2024]
Abstract
Despite the well-established connection between systematic metabolic abnormalities and the pathophysiology of pituitary adenoma (PA), current metabolomic studies have reported an extremely limited number of metabolites associated with PA. Moreover, there was very little consistency in the identified metabolite signatures, resulting in a lack of robust metabolic biomarkers for the diagnosis and treatment of PA. Herein, we performed a global untargeted plasma metabolomic profiling on PA and identified a highly robust metabolomic signature based on a strategy. Specifically, this strategy is unique in (1) integrating repeated random sampling and a consensus evaluation-based feature selection algorithm and (2) evaluating the consistency of metabolomic signatures among different sample groups. This strategy demonstrated superior robustness and stronger discriminative ability compared with that of other feature selection methods including Student's t-test, partial least-squares-discriminant analysis, support vector machine recursive feature elimination, and random forest recursive feature elimination. More importantly, a highly robust metabolomic signature comprising 45 PA-specific differential metabolites was identified. Moreover, metabolite set enrichment analysis of these potential metabolic biomarkers revealed altered lipid metabolism in PA. In conclusion, our findings contribute to a better understanding of the metabolic changes in PA and may have implications for the development of diagnostic and therapeutic approaches targeting lipid metabolism in PA. We believe that the proposed strategy serves as a valuable tool for screening robust, discriminating metabolic features in the field of metabolomics.
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Affiliation(s)
- Jing Tang
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
- Department of Bioinformatics, Chongqing Medical University, Chongqing 400016, China
| | - Minjie Mou
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Xin Zheng
- Multidisciplinary Center for Pituitary Adenoma of Chongqing, Department of Neuosurgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Jin Yan
- Multidisciplinary Center for Pituitary Adenoma of Chongqing, Department of Neuosurgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Ziqi Pan
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Jinsong Zhang
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Bo Li
- School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
| | - Qingxia Yang
- School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
| | - Yunxia Wang
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Ying Zhang
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Song Li
- Multidisciplinary Center for Pituitary Adenoma of Chongqing, Department of Neuosurgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Hui Yang
- Multidisciplinary Center for Pituitary Adenoma of Chongqing, Department of Neuosurgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Feng Zhu
- College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
- Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou 330110, China
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15
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Yit LFN, Li Y. A Review of the Evolving Role of Radiotherapy in the Treatment of Neuroendocrine Neoplasms. Neuroendocrinology 2024; 114:856-865. [PMID: 38432216 DOI: 10.1159/000538140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 02/20/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are rare tumours that develop from neuroendocrine cells in various parts of the body. The management of this disease poses a significant challenge because of the heterogeneous clinical presentation and varying degrees of aggressiveness. A multidisciplinary approach is often required in complex clinical situations. Radiotherapy (RT) plays a key role in managing NETs in both curative and palliative settings. SUMMARY In this review, we summarize and discuss recent developments in the field of advanced RT in early-stage, locally advanced, and metastatic NENs. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NENs.
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Affiliation(s)
- Ling Fung Nelson Yit
- Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Youquan Li
- Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
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16
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Bruzaite A, Gedvilaite G, Kriauciuniene L, Liutkeviciene R. Association of KDR (rs2071559, rs1870377), CFH (rs1061170, rs1410996) genes variants and serum levels with pituitary adenoma. Mol Genet Genomic Med 2024; 12:e2289. [PMID: 37803932 PMCID: PMC10767405 DOI: 10.1002/mgg3.2289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 09/09/2023] [Accepted: 09/19/2023] [Indexed: 10/08/2023] Open
Abstract
INTRODUCTION Pituitary adenomas (PA) are slow-growing, benign tumors that usually do not metastasize to other body organs. Although they are referred to as benign, tumor growth can eventually put pressure on nearby structures, spread to surrounding tissues, and cause symptoms. The exact cause of PA is unknown, and the pathogenesis is multifactorial. METHODS Our study included PA patients and healthy volunteers. Genomic DNA was extracted using the DNA salting-out method. All participants were genotyped for the KDR rs2071559, rs1870377, CFH rs1061170, and rs1410996 polymorphisms. Serum levels of KDR and CFH were examined using the ELISA method. RESULTS The results of the present study showed that KDR rs2071559 A allele was associated with the occurrence of PA, hormonally active PA, invasive PA, and PA without recurrence development. KDR rs1870377 increased the probability of invasive PA and PA recurrence. CFH rs1061170 C allele was associated with hormonally active PA and the T allele was associated with non-invasive PA development. CONCLUSION KDR rs2071559, rs1870377, and CFH rs1061170 could be potential biomarkers associated with PA.
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Affiliation(s)
- Akvile Bruzaite
- Ophthalmology LaboratoryNeuroscience Institute, Lithuanian University of Health Sciences, Medical AcademyKaunasLithuania
| | - Greta Gedvilaite
- Ophthalmology LaboratoryNeuroscience Institute, Lithuanian University of Health Sciences, Medical AcademyKaunasLithuania
| | - Loresa Kriauciuniene
- Ophthalmology LaboratoryNeuroscience Institute, Lithuanian University of Health Sciences, Medical AcademyKaunasLithuania
| | - Rasa Liutkeviciene
- Ophthalmology LaboratoryNeuroscience Institute, Lithuanian University of Health Sciences, Medical AcademyKaunasLithuania
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17
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Пронин ВС, Анциферов МБ, Алексеева ТМ, Пронин ЕВ, Лапшина АМ, Урусова ЛС. [Unification of pathomorphological examination of patients with neuroendocrine tumors of the pituitary gland. Controversial issues of the new classification]. PROBLEMY ENDOKRINOLOGII 2023; 70:31-45. [PMID: 39069771 PMCID: PMC11334236 DOI: 10.14341/probl13376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/05/2023] [Accepted: 11/14/2023] [Indexed: 07/30/2024]
Abstract
The progressive improvement of the classification using modern analytical methods is an essential tool for the development of precise and personalized approaches to the treatment of pituitary adenomas. In recent years, endocrinologists have witnessed evolutionary changes that have occurred in the histopathological identification of pituitary neoplasms, revealing new possibilities for studying tumorigenesis and predicting biological behavior.The paper considers the historical aspects of the gradual improvement of the classification of pituitary adenomas, as well as the new international 2022 WHO classification, according to which pituitary adenomas are included in the list of neuroendocrine tumors (PitNETs) to reflect the biological aggressiveness of some non-metastatic pituitary adenomas. The characteristics of pituitary adenoma are presented, as well as a list of histological subtypes of aggressive neuroendocrine tumors of the pituitary gland, marked by the main potentials for invasive growth, an increased risk of recurrence and a negative clinical prognosis.The expediency of changing the definition of «pituitary adenoma» to «neuroendocrine tumor» is discussed. It is emphasized that the introduction of a unified clinical, laboratory and morphological protocol into national clinical practice will help provide comparable comparative studies on the prognosis of the disease and the effectiveness of secondary therapy and also contribute to adequate management of potentially aggressive PitNETs.
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Affiliation(s)
- В. С. Пронин
- Российская медицинская академия непрерывного профессионального образования;
Эндокринологический диспансер Департамента здравоохранения города Москвы
| | - М. Б. Анциферов
- Российская медицинская академия непрерывного профессионального образования;
Эндокринологический диспансер Департамента здравоохранения города Москвы
| | - Т. М. Алексеева
- Эндокринологический диспансер Департамента здравоохранения города Москвы
| | - Е. В. Пронин
- Эндокринологический диспансер Департамента здравоохранения города Москвы
| | - А. М. Лапшина
- Национальный медицинский исследовательский центр эндокринологии
| | - Л. С. Урусова
- Национальный медицинский исследовательский центр эндокринологии
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18
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McKevitt C, Gabriel E, Marenco-Hillembrand L, Otamendi-Lopez A, Jeevaratnam S, Almeida JP, Samson S, Chaichana KL. Supervised machine learning to validate a novel scoring system for the prediction of disease remission of functional pituitary adenomas following transsphenoidal surgery. Sci Rep 2023; 13:15409. [PMID: 37717023 PMCID: PMC10505180 DOI: 10.1038/s41598-023-42157-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/06/2023] [Indexed: 09/18/2023] Open
Abstract
Functional pituitary adenomas (FPAs) are associated with hormonal hypersecretion resulting in systemic endocrinopathies and increased mortality. The heterogenous composition of the FPA population has made modeling predictive factors of postoperative disease remission a challenge. Here, we aim to define a novel scoring system predictive of disease remission following transsphenoidal surgery (TSS) for FPAs and validate our process using supervised machine learning (SML). 392 patients with FPAs treated at one of the three Mayo Clinic campuses were retrospectively reviewed. Variables found significant on multivariate analysis were incorporated into our novel Pit-SCHEME score. The Pit-SCHEME score with a cut-off value ≥ 6 achieved a sensitivity of 86% and positive likelihood ratio of 2.88. In SML models, without the Pit-SCHEME score, the k-nearest neighbor (KNN) model achieved the highest accuracy at 75.6%. An increase in model sensitivity was achieved with inclusion of the Pit-SCHEME score with the linear discriminant analysis (LDA) model achieving an accuracy of 86.9%, which suggests the Pit-SCHEME score is the variable of most importance for prediction of postoperative disease remission. Ultimately, these results support the potential clinical utility of the Pit-SCHEME score and its prospective future for aiding in the perioperative decision making in patients with FPAs.
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Affiliation(s)
- Chase McKevitt
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
| | - Ellie Gabriel
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Lina Marenco-Hillembrand
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Andrea Otamendi-Lopez
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Suren Jeevaratnam
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Joao Paulo Almeida
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Susan Samson
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Kaisorn L Chaichana
- Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
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19
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Li JY, Chen J, Liu J, Zhang SZ. Simultaneous rectal neuroendocrine tumors and pituitary adenoma: A case report and review of literature. World J Gastroenterol 2023; 29:5082-5090. [PMID: 37753367 PMCID: PMC10518740 DOI: 10.3748/wjg.v29.i34.5082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/09/2023] [Accepted: 08/18/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Neuroendocrine tumors (NET) are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body. Acromegaly, a rare and slowly progressive disorder, usually results from a growth hormone (GH)-secreting pituitary adenoma. CASE SUMMARY We herein describe a 38-year-old patient who was initially diagnosed with diabetes. During colonoscopy, two bulges were identified and subsequently removed through endoscopic submucosal dissection. Following the surgical intervention, the excised tissue samples were examined and confirmed to be grade 2 NET. 18F-ALF-NOTATATE positron emission tomography-computed tomography (PET/CT) and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes, prompting laparoscopic low anterior resection with total mesorectal excision. The patient later returned to the hospital because of hyperglycemia and was found to have facial changes, namely a larger nose, thicker lips, and mandibular prognathism. Laboratory tests and magnetic resonance imaging (MRI) suggested a GH-secreting pituitary adenoma. The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach. Whole-exome sequencing analysis revealed no genetic abnormalities. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION 18F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.
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Affiliation(s)
- Jing-Yi Li
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Jie Chen
- Department of Neuroendocrine Tumor, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Jun Liu
- Department of Gastroenterology, Shanxi Bethune Hospital, Taiyuan 030032, Shanxi Province, China
| | - Su-Zhen Zhang
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
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20
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Robertson IJ, Gregory TA, Waguespack SG, Penas-Prado M, Majd NK. Recent Therapeutic Advances in Pituitary Carcinoma. JOURNAL OF IMMUNOTHERAPY AND PRECISION ONCOLOGY 2023; 6:74-83. [PMID: 37214211 PMCID: PMC10195013 DOI: 10.36401/jipo-22-25] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/07/2022] [Accepted: 10/18/2022] [Indexed: 05/24/2023]
Abstract
Pituitary carcinoma (PC) is a rare, aggressive malignancy that comprises 0.1-0.2% of all pituitary tumors. PC is defined anatomically as a pituitary tumor that metastasizes outside the primary intrasellar location as noncontiguous lesions in the central nervous system or as metastases to other organs. Similar to pituitary adenoma, PC originates from various cell types of the pituitary gland and can be functioning or nonfunctioning, with the former constituting the majority of the cases. Compression of intricate skull-based structures, excessive hormonal secretion, impaired pituitary function from therapy, and systemic metastases lead to debilitating symptoms and a poor survival outcome in most cases. PC frequently recurs despite multimodality treatments, including surgical resection, radiotherapy, and biochemical and cytotoxic treatments. There is an unmet need to better understand the pathogenesis and molecular characterization of PC to improve therapeutic strategies. As our understanding of the role of signaling pathways in the tumorigenesis of and malignant transformation of PC evolves, efforts have focused on targeted therapy. In addition, recent advances in the use of immune checkpoint inhibitors to treat various solid cancers have led to an interest in exploring the role of immunotherapy for the treatment of aggressive refractory pituitary tumors. Here, we review our current understanding of the pathogenesis, molecular characterization, and treatment of PC. Particular attention is given to emerging treatment options, including targeted therapy, immunotherapy, and peptide receptor radionuclide therapy.
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Affiliation(s)
- Ian J. Robertson
- Department of Internal Medicine, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Timothy A. Gregory
- Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Steven G. Waguespack
- Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Marta Penas-Prado
- Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Nazanin K. Majd
- Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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21
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De Alcubierre D, Puliani G, Cozzolino A, Hasenmajer V, Minnetti M, Sada V, Martines V, Zaccagnino A, Ruggeri AG, Pofi R, Sbardella E, Venneri MA. Pituitary adenoma consistency affects postoperative hormone function: a retrospective study. BMC Endocr Disord 2023; 23:92. [PMID: 37101307 PMCID: PMC10131333 DOI: 10.1186/s12902-023-01334-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 04/05/2023] [Indexed: 04/28/2023] Open
Abstract
BACKGROUND Tumor consistency recently emerged as a key factor in surgical planning for pituitary adenomas, but its impact on postoperative endocrine function is still unclear. Our study aimed to evaluate the impact of tumor consistency on the development of postoperative pituitary deficiencies. METHODS Single-center, retrospective analysis of consecutive pituitary surgeries performed between January 2017 and January 2021 at Policlinico Umberto I in Rome. All patients underwent radiological and biochemical evaluations at baseline, and hormone assessments 3 and 6 months after pituitary surgery. Postoperative MRI studies were used to determine resection rates following surgery. Data on tumor consistency, macroscopic appearance, neurosurgical approach, and intraoperative complications were collected. RESULTS Fifty patients [24 women, mean age 57 ± 13 years, median tumor volume 4800 mm3 [95% CI 620-8828], were included. Greater tumor volume (χ2 = 14.621, p = 0.006) and male sex (χ2 = 12.178, p < 0.001) were associated with worse preoperative endocrine function. All patients underwent transsphenoidal adenomectomy. Fibrous consistency was observed in 10% of patients and was associated with a Ki-67 greater than 3% (χ2 = 8.154, p = 0.04), greater risk of developing postoperative hormone deficiencies (χ2 = 4.485, p = 0.05, OR = 8.571; 95% CI: 0.876-83.908), and lower resection rates (χ2 = 8.148, p = 0.004; OR 1.385, 95% CI; 1.040-1.844). Similarly, worse resection rates were observed in tumors with suprasellar extension (χ2 = 5.048, p = 0.02; OR = 6.000, 95% CI; 1.129-31.880) and CSI (χ2 = 4.000, p = 0.04; OR = 3.857, 95% CI; 0.997-14.916). CONCLUSIONS Tumor consistency might provide useful information about postoperative pituitary function, likely due to its impact on surgical procedures. Further prospective studies with larger cohorts are needed to confirm our preliminary findings.
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Affiliation(s)
- Dario De Alcubierre
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Giulia Puliani
- Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Alessia Cozzolino
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Valeria Hasenmajer
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Marianna Minnetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Valentina Sada
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Antonella Zaccagnino
- Department of Neurology and Psychiatry-Neurosurgery Unit, Sapienza University of Rome, Rome, Italy
| | - Andrea Gennaro Ruggeri
- Department of Neurology and Psychiatry-Neurosurgery Unit, Sapienza University of Rome, Rome, Italy
| | - Riccardo Pofi
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
| | - Emilia Sbardella
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
| | - Mary Anna Venneri
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
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22
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He Y, Gao YT, Sun L. Functioning gonadotroph adenoma with hyperestrogenemia and ovarian hyperstimulation in a reproductive-aged woman: A case report and review of literature. World J Clin Cases 2023; 11:1341-1348. [PMID: 36926127 PMCID: PMC10013118 DOI: 10.12998/wjcc.v11.i6.1341] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 12/28/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND Functioning gonadotroph adenomas are extremely rare pituitary tumors that secrete gonadotropins and exhibit distinct clinical manifestations. Here, we report a case of functioning gonadotroph adenoma in a reproductive-aged woman and discuss its diagnosis and management.
CASE SUMMARY A 21-year-old female patient with abdominal pain, irregular menstruation, hyperestrogenemia, and an ovarian mass was included. Brain magnetic resonance imaging (MRI) revealed a pituitary macroadenoma, and transsphenoidal surgery relieved her clinical symptoms. Before transsphenoidal surgery, plasma CA125, estradiol levels were elevated, while prolactin, luteinizing hormone, follicle-stimulating hormone, PROG, cortisol, FT4, thyroid-stimulating hormone, parathyroid hormone, and GH levels were maintained at normal levels. After transsphenoidal surgery, the patient was diagnosed with a functioning gonadotroph adenoma. During follow-up, pelvic ultrasound confirmed normal-sized ovaries in the patient, the menstrual cycle returned to regular, and her hormones were maintained within a normal range. There was no evidence of tumor recurrence after two years of follow-up.
CONCLUSION Early diagnosis of functioning gonadotroph adenomas should be considered in patients with hyperestrogenism, irregular menstruation, large or recurrent ovarian cysts, and visual field defects. Pituitary MRI should be performed, and transsphenoidal surgery is recommended for the management of this disease.
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Affiliation(s)
- Ying He
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Yu-Tao Gao
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Li Sun
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
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23
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Chen YJ, Li L. A Complete Form of Pachydermoperiostosis Accompanied by a Pituitary Microadenoma. Clin Cosmet Investig Dermatol 2023; 16:47-52. [PMID: 36636633 PMCID: PMC9830955 DOI: 10.2147/ccid.s389766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 12/30/2022] [Indexed: 01/07/2023]
Abstract
Pachydermoperiostosis is a rare genetic disease that is associated with HPGD (15-hydroxyprostaglandin dehydrogenase) and SLCO2A1 (solute carrier organic anion transporter family member 2A1) gene mutations. It is characterized by three major phenotypes, namely, pachydermia, periostosis, and digital clubbing. Clinically, misdiagnoses such as acromegaly and thyroid acropachy are commonly confused with pachydermoperiostosis. Integral medical history, physical examination, endocrinological tests, and multiple disciplinary cooperation are extremely significant in the accurate diagnosis of pachydermoperiostosis. The co-existence of pachydermoperiostosis and pituitary adenoma is rarely recorded and discussed. In this case, we present a young male patient with a complete form of pachydermoperiostosis and a nonfunctional pituitary microadenoma, which has rarely been reported.
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Affiliation(s)
- Yan Jing Chen
- Department of Dermatology and Venereology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Li Li
- Department of Dermatology and Venereology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China,Correspondence: Li Li, Department of dermatology and venereology, West China Hospital, Sichuan University, Guoxue Alley No. 37, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 18980601692, Email
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24
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Wang M, Ji C, Zhang Y, Zhang Z, Zhang Y, Guo H, Qiao N, Zhou X, Cao X, Ye Z, Yu Y, Melnikov V, Gong W, He M, Zhang Z, Zhao Y, Wang X, Wei G, Ye Z. Global changes in chromatin accessibility and transcription in growth hormone-secreting pituitary adenoma. Endocrine 2022; 78:329-342. [PMID: 35947334 PMCID: PMC9584994 DOI: 10.1007/s12020-022-03155-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 07/25/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA. METHODS Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA. RESULTS Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site. CONCLUSIONS Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease.
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Affiliation(s)
- Meng Wang
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chenxing Ji
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
| | - Yichao Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
| | - Zhiqiang Zhang
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yu Zhang
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Huiping Guo
- School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Nidan Qiao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Xiang Zhou
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Xiaoyun Cao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Zhen Ye
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
| | - Yifei Yu
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Vladimir Melnikov
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei Gong
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Min He
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhaoyun Zhang
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yao Zhao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Sate Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Neurosurgical Institute of Fudan University, Fudan University, Shanghai, China
| | - Xuelong Wang
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
| | - Gang Wei
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
| | - Zhao Ye
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.
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25
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Birkenbeuel JL, Lehrich BM, Goshtasbi K, Abiri A, Hsu FPK, Kuan EC. Refusal of Surgery in Pituitary Adenoma Patients: A Population-Based Analysis. Cancers (Basel) 2022; 14:cancers14215348. [PMID: 36358767 PMCID: PMC9656152 DOI: 10.3390/cancers14215348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/26/2022] [Accepted: 10/27/2022] [Indexed: 12/04/2022] Open
Abstract
We characterized the clinical and sociodemographic factors predictive of surgery refusal in pituitary adenoma (PA) patients. We queried the National Cancer Database (NCDB) to identify adult PA patients treated from 2004−2015 receiving or refusing surgery. Multivariate logistic regression and Cox proportional-hazards analysis identified clinical and/or sociodemographic factors predictive of surgery refusal or mortality, respectively. Of the 34,226 patients identified, 280 (0.8%) refused surgery. On multivariate logistic regression, age > 65 (OR: 2.64; p < 0.001), African American race (OR: 1.70; p < 0.001), Charlson-Deyo Comorbidity (C/D) Index > 2 (OR: 1.52; p = 0.047), and government insurance (OR: 2.03; p < 0.001) or being uninsured (OR: 2.16; p = 0.03) were all significantly associated with surgery refusal. On multivariate cox-proportional hazard analysis, age > 65 (HR: 2.66; p < 0.001), tumor size > 2 cm (HR: 1.30; p < 0.001), C/D index > 1 (HR: 1.53; p < 0.001), having government insurance (HR: 1.66; p < 0.001) or being uninsured (HR: 1.67; p < 0.001), and surgery refusal (HR: 2.28; p < 0.001) were all significant predictors of increased mortality. Macroadenoma patients receiving surgery had a significant increase in overall survival (OS) compared to those who refused surgery (p < 0.001). There are significant sociodemographic factors that influence surgery refusal in PA patients. An individualized approach is warranted that considers functional status, clinical presentations, and patient choice.
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Affiliation(s)
- Jack L. Birkenbeuel
- Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, CA 92868, USA
| | - Brandon M. Lehrich
- Medical Scientist Training Program, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Khodayar Goshtasbi
- Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, CA 92868, USA
| | - Arash Abiri
- Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, CA 92868, USA
| | - Frank P. K. Hsu
- Department of Neurosurgery, University of California, Irvine, CA 92868, USA
| | - Edward C. Kuan
- Department of Otolaryngology–Head and Neck Surgery, University of California, Irvine, CA 92868, USA
- Department of Neurosurgery, University of California, Irvine, CA 92868, USA
- Correspondence: ; Tel.: +1-714-456-5753
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SFRP2 is a Novel Diagnostic Biomarker and Suppresses the Proliferation of Pituitary Adenoma. JOURNAL OF ONCOLOGY 2022; 2022:4272525. [PMID: 36276274 PMCID: PMC9586780 DOI: 10.1155/2022/4272525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/02/2022] [Accepted: 10/06/2022] [Indexed: 11/18/2022]
Abstract
Pituitary adenoma (PA) constitutes one of the most common intracranial tumors. The present study was designed to identify potential diagnostic markers for PA. We used gene expression profiles (GEO: GSE26966 and GEO: GSE63357 datasets) derived from human PA and nontumor samples that were made freely accessible by the gene expression omnibus (GEO) datasets. Differentially expressed genes (DEGs) were screened between 14 normal specimens and 34 PA specimens by the use of the limma package of the R. The diagnostic genes were determined using a LASSO regression model and SVM-RFE analysis. SFRP2 expression in PA cells was analyzed using RT-PCR, and the effect of SFRP2 dysregulation on PA cell proliferation was measured using CCK-8 analysis. In this study, 361 DEGs were identified: 309 genes were downregulated and 52 genes were upregulated. The results of KEGG assays revealed that the 361 DEGs were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, growth hormone synthesis, secretion and action, and AGE-RAGE signaling pathway in diabetic complications. Results from the LASSO regression model and the SVM-RFE analysis indicated that LOC101060391 and SFRP2 were diagnostic genes. In contrast to normal tissue, the expressions of LOC101060391 and SFRP2 were much lower in PA samples. According to the ROC assays, high LOC101060391 and SFRP2 expression had an AUC value >0.9 for PA. Upregulation of SFRP2 distinctly inhibited the proliferative capacity of PA cells, as shown by CCK-8 analysis. Furthermore, knockdown of SFRP2 had an influence on cell growth in both the AtT-20 and HP75 cell lines. Taken together, our findings indicate that LOC101060391 and SFRP2 have diagnostic potential for PA. Furthermore, SFRP2 may be an antioncogene and a therapeutic target for PA.
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Wu J, Zhang B, Shao D, Ji S, Li Y, Xie S, Jiang Z. Analysis of neuroendoscopy for the treatment of macroadenomas and giant pituitary adenomas. Front Surg 2022; 9:956345. [PMID: 36034373 PMCID: PMC9403245 DOI: 10.3389/fsurg.2022.956345] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
Objective This study investigated the use and effectiveness of endoscopic transnasal, transsphenoidal surgery, a minimally invasive method for the treatment of macroadenomas and giant pituitary a denomas, in a medical setting. The surgical results of 429 patients who received neuroendoscopic treatment of macroadenomas or giant pituitary adenomas were evaluated, and the experiences and lessons learned from treatment complications were assessed. Patients and methods From January 2012 to December 2021, 429 patients with macroadenomas or giant pituitary adenomas, including 60 patients with giant adenomas (diameter ≥4 cm) and 369 patients with macroadenomas (diameter 1–4 cm), received a 3D head CT, a MRI with contrast enhancement, and an endocrinology examination prior to surgery. Preoperative clinical and radiological features, visual measurements, hormone levels, length of stay, length of surgery, postoperative stay, visual and hormone outcomes, resection range, complication and recurrence rates, and routine patient information were recorded. The patients were followed up for 6–72 months (median = 40 months). Results Of 429 patients with macroadenomas or giant pituitary adenomas who received neuroendoscopic treatment, 348 (81.12%) had gross-total resections (GTR), 53 (12.35%) had near-total resections (NTR), and 28 (6.53%) had subtotal resections. There were 138 cases of post-operative diabetes insipidus (32.17%), including 7 cases of permanent diabetes insipidus (1.63%), 16 cases of nasal hemorrhage (3.73%), 39 cases of intraoperative cerebrospinal fluid leakage (9.09%), 4 cases of intracranial infection (0.9%), 16 cases of hypophysis (3.7%), and 15 cases of anosmia (3.50%). The clinical symptoms and endocrinology indices of the patients improved after surgery, and all patients were discharged 5–18 days (8.36 ± 2.65) postop. Conclusion Neuroendoscopy is a safe operation with a short recovery period and hospital stay and is thus an effective method to treat macroadenomas and giant pituitary adenomas. Preoperative evaluation and prediction can help to accurately address possible intraoperative situations and improve GTR.
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Affiliation(s)
- Junyong Wu
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Binbin Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Dongqi Shao
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shuxin Ji
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yu Li
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shan Xie
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhiquan Jiang
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Correspondence: Zhiquan Jiang
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Koskay G, Opperman P, Mezzacappa FM, Surdell D. Decision-Making and Management in a Patient With Coexistent Colloid Cyst and Pituitary Macroadenoma: A Case Report. Cureus 2022; 14:e22884. [PMID: 35399429 PMCID: PMC8980217 DOI: 10.7759/cureus.22884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2022] [Indexed: 11/06/2022] Open
Abstract
The coexistence of separate and distinct primary intracranial tumors is rare. Specifically, there are no previous reports of a colloid cyst coexisting with a pituitary macroadenoma. We present the case of a 40-year-old male with a colloid cyst associated with mild enlargement of the right lateral ventricle and a coexistent pituitary macroadenoma with compression of the optic apparatus. An endoscopic endonasal transsphenoidal surgery (EETS) for resection of the pituitary mass was performed first due to the patient’s complaints of acute visual changes. He then underwent a right frontal craniotomy for resection of the colloid cyst one month later. The patient recovered without residual deficits in vision, and he did not require ventricular shunting after removal of the colloid cyst. We aimed to discuss our decision-making process and the management of these coexistent lesions.
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Yan JL, Chen MY, Chen YL, Chuang CC, Hsu PW, Wei KC, Chang CN. Surgical Outcome and Evaluation of Strategies in the Management of Growth Hormone-Secreting Pituitary Adenomas After Initial Transsphenoidal Pituitary Adenectomy Failure. Front Endocrinol (Lausanne) 2022; 13:756855. [PMID: 35498411 PMCID: PMC9048041 DOI: 10.3389/fendo.2022.756855] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 03/09/2022] [Indexed: 12/02/2022] Open
Abstract
Acromegaly is a systemic disease that requires multidisciplinary treatment to achieve the best clinical outcome. This study aimed to evaluate the outcomes of the endoscopic transsphenoidal approach (TSA) as the primary treatment for somatotroph adenomas and further investigate patients who had suboptimal surgical results. This retrospective study included 83 patients with somatotroph adenomas treated by TSA at our institution from 1999 to 2010. Biochemical remission was defined as hGH <1 and <2.5 ng/ml. Factors associated with failure of TSA and strategy of secondary treatments for refractory and recurrent disease were analyzed. The mean age of patients was 41.1 ± 11.3 years, and the mean follow-up time was 54.2 ± 44.3 months. Approximately 44.5% of patients had residual tumors after TSA. Larger tumor size, higher GH level before the operation, and the existence of residual tumors were associated with TSA failure. Forty-one patients had an inadequate response to TSA or a recurrent lesion, and of these patients, 37 had residual tumor after TSA. Octreotide results in good outcomes in the treatment of DGSA patients, and SRS/EXRT generates good results in treating patients who receive second treatments when remission cannot be reached 6 months after TSA operation.
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Affiliation(s)
- Jiun-Lin Yan
- Department of Neurosurgery, Keelung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Keelung, Taiwan
- Chang Gung University, College of Medicine, Taoyuan, Taiwan
- *Correspondence: Jiun-Lin Yan, ; Chen-Nen Chang,
| | - Mao-Yu Chen
- Department of Neurosurgery, Keelung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Keelung, Taiwan
| | - Yao-Liang Chen
- Department of Radiology, Keelung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Keelung, Taiwan
| | - Chi-Cheng Chuang
- Chang Gung University, College of Medicine, Taoyuan, Taiwan
- Department of Neurosurgery, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
| | - Peng-Wei Hsu
- Chang Gung University, College of Medicine, Taoyuan, Taiwan
- Department of Neurosurgery, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
| | - Kuo-Chen Wei
- Chang Gung University, College of Medicine, Taoyuan, Taiwan
- Department of Radiology, Keelung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Keelung, Taiwan
| | - Chen-Nen Chang
- Department of Neurosurgery, Keelung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Keelung, Taiwan
- Chang Gung University, College of Medicine, Taoyuan, Taiwan
- Department of Neurosurgery, Xiamen Chang Gung Hospital, Xiamen, Taiwan
- *Correspondence: Jiun-Lin Yan, ; Chen-Nen Chang,
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Valea A, Sandru F, Petca A, Dumitrascu MC, Carsote M, Petca RC, Ghemigian A. Aggressive prolactinoma (Review). Exp Ther Med 2021; 23:74. [PMID: 34934445 DOI: 10.3892/etm.2021.10997] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/05/2021] [Indexed: 12/22/2022] Open
Abstract
Aggressive prolactinoma (APRL) is a subgroup of aggressive pituitary tumors (accounting for 10% of all hypophyseal neoplasia) which are defined by: invasion based on radiological and/or histological features, a higher proliferation profile when compared to typical adenomas and rapidly developing resistance to standard medication/protocols in addition to an increased risk of early recurrence. This is a narrative review focusing on APRL in terms of both presentation and management. Upon admission, the suggestive features may include increased serum prolactin with a large tumor diameter (mainly >4 cm), male sex, early age at diagnosis (<20 years), and genetic predisposition [multiple endocrine neoplasia type 1 (MEN1), aryl hydrocarbon receptor interacting protein (AIP), succinate dehydrogenase (SDHx) gene mutations]. Potential prognostic factors are indicated by assessment of E-cadherin, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) status. Furthermore, during management, APRL may be associated with dopamine agonist (DA) resistance (described in 10-20% of all prolactinomas), post-hypophysectomy relapse, mitotic count >2, Ki-67 proliferation index ≥3%, the need for radiotherapy, lack of response in terms of controlling prolactin levels and tumor growth despite multimodal therapy. However, none of these as an isolated element serves as a surrogate of APRL diagnosis. A fourth-line therapy is necessary with temozolomide, an oral alkylating chemotherapeutic agent, that may induce tumor reduction and serum prolactin reduction in 75% of cases but only 8% have a normalization of prolactin levels. Controversies surrounding the duration of therapy still exist; also regarding the fifth-line therapy, post-temozolomide intervention. Recent data suggest alternatives such as somatostatin analogues (pasireotide), checkpoint inhibitors (ipilimumab, nivolumab), tyrosine kinase inhibitors (TKIs) (lapatinib), and mTOR inhibitors (everolimus). APRL represents a complex condition that is still challenging, and multimodal therapy is essential.
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Affiliation(s)
- Ana Valea
- Department of Endocrinology, 'I. Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.,Department of Endocrinology, Clinical County Hospital, 400000 Cluj-Napoca, Romania
| | - Florica Sandru
- Department of Dermatology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Dermatology, 'Elias' University Emergency Hospital, 011461 Bucharest, Romania
| | - Aida Petca
- Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Obstetrics and Gynecology, 'Elias' University Emergency Hospital, 011461 Bucharest, Romania
| | - Mihai Cristian Dumitrascu
- Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Obstetrics and Gynecology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Mara Carsote
- Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Endocrinology, 'C. I. Parhon' National Institute of Endocrinology, 011863 Bucharest, Romania
| | - Razvan-Cosmin Petca
- Department of Urology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Urology, 'Prof. Dr. Theodor Burgele' Clinical Hospital, 061344 Bucharest, Romania
| | - Adina Ghemigian
- Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Endocrinology, 'C. I. Parhon' National Institute of Endocrinology, 011863 Bucharest, Romania
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Zou Y, Li D, Gu J, Chen S, Wen X, Dong J, Jiang X. The recurrence of prolactinoma after withdrawal of dopamine agonist: a systematic review and meta-analysis. BMC Endocr Disord 2021; 21:225. [PMID: 34774043 PMCID: PMC8590353 DOI: 10.1186/s12902-021-00889-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/28/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Prolactinoma is the major cause of hyperprolactinemia, and dopamine agonists (DAs) are generally the first-line treatment for them. Several studies have reviewed the recurrent rate of hyperprolactinemia after DAs withdrawal. However, few of them have concerned the recurrence risk of prolactinoma following the withdrawal of DAs. METHODS Three medical databases, PubMed, EMBASE and Cochrane library, were retrieved up to February, 14, 2021 to identify studies related to recurrence of prolactinoma and withdrawal of DAs. Statistical analyses including meta-analysis, sensitivity analysis, meta-regression, funnel plot and Egger test were performed through software R. RESULTS A total of 3225 studies were retrieved from the three data bases, and 13 studies consisted of 616 patients and 19 arms were finally included in this systematic analysis. There was no significant heterogeneity among the included studies, and fixed effect model was thus used. The pooled recurrence proportion of prolactinoma after withdrawal of DA was 2% with a 95% confidence interval (CI) of 1-3%. CONCLUSION Our study showed a very low recurrent rate of prolactinomas after DAs withdrawal. Much more prospective studies with larger cases and longer follow-up period are encouraged to confirm our finding. TRIAL REGISTRATION Registration number CRD42021245888 (PROSPERO).
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Affiliation(s)
- Yunzhi Zou
- Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Depei Li
- Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Jiayu Gu
- Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Siyu Chen
- Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Xia Wen
- Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Jiajun Dong
- Jiangmen Central Hospital, Affiliated Jiangmen hospital of Sun Yat-Sen University, Jiangmen, 519000, China.
| | - Xiaobing Jiang
- Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
- Jiangmen Central Hospital, Affiliated Jiangmen hospital of Sun Yat-Sen University, Jiangmen, 519000, China.
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32
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Alvarez-Payares JC, Bello-Simanca JD, De La Peña-Arrieta EDJ, Agamez-Gomez JE, Garcia-Rueda JE, Rodriguez-Arrieta A, Rodriguez-Arrieta LA. Common Pitfalls in the Interpretation of Endocrine Tests. Front Endocrinol (Lausanne) 2021; 12:727628. [PMID: 34557164 PMCID: PMC8453144 DOI: 10.3389/fendo.2021.727628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/23/2021] [Indexed: 11/15/2022] Open
Abstract
Endocrine tests are the cornerstone of diagnosing multiple diseases that primary care physicians are frequently faced with. Some of these tests can be affected by situations that affect the proper interpretation, leading to incorrect diagnoses and unnecessary treatment, such as the interference of biotin with thyroid function test, falsely elevated prolactin values in presence of macroprolactinemia or falsely normal due to the "hook effect" in macroprolactinomas. Recognizing these situations is essential for the clinician to make an adequate interpretation of these tests as well as an accurate diagnosis that guarantees the best outcomes for the patient.
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Affiliation(s)
- Jose C. Alvarez-Payares
- Internal Medicine Department, Faculty of Medicine, University of Antioquia, Medellin, Colombia
- Internal Medicine Service, Institución Prestadora de Servicios (IPS) Universitaria - Clínica León XIII, Medellin, Colombia
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Shahrestani S, Cardinal T, Micko A, Strickland BA, Pangal DJ, Kugener G, Weiss MH, Carmichael J, Zada G. Neural network modeling for prediction of recurrence, progression, and hormonal non-remission in patients following resection of functional pituitary adenomas. Pituitary 2021; 24:523-529. [PMID: 33528731 DOI: 10.1007/s11102-021-01128-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE Functional pituitary adenomas (FPAs) cause severe neuro-endocrinopathies including Cushing's disease (CD) and acromegaly. While many are effectively cured following FPA resection, some encounter disease recurrence/progression or hormonal non-remission requiring adjuvant treatment. Identification of risk factors for suboptimal postoperative outcomes may guide initiation of adjuvant multimodal therapies. METHODS Patients undergoing endonasal transsphenoidal resection for CD, acromegaly, and mammosomatotroph adenomas between 1992 and 2019 were identified. Good outcomes were defined as hormonal remission without imaging/biochemical evidence of disease recurrence/progression, while suboptimal outcomes were defined as hormonal non-remission or MRI evidence of recurrence/progression despite adjuvant treatment. Multivariate regression modeling and multilayered neural networks (NN) were implemented. The training sets randomly sampled 60% of all FPA patients, and validation/testing sets were 20% samples each. RESULTS 348 patients with mean age of 41.7 years were identified. Eighty-one patients (23.3%) reported suboptimal outcomes. Variables predictive of suboptimal outcomes included: Requirement for additional surgery in patients who previously had surgery and continue to have functionally active tumor (p = 0.0069; OR = 1.51, 95%CI 1.12-2.04), Preoperative visual deficit not improved after surgery (p = 0.0033; OR = 1.12, 95%CI 1.04-1.20), Transient diabetes insipidus (p = 0.013; OR = 1.27, 95%CI 1.05-1.52), Higher MIB-1/Ki-67 labeling index (p = 0.038; OR = 1.08, 95%CI 1.01-1.15), and preoperative low cortisol axis (p = 0.040; OR = 2.72, 95%CI 1.06-7.01). The NN had overall accuracy of 87.1%, sensitivity of 89.5%, specificity of 76.9%, positive predictive value of 94.4%, and negative predictive value of 62.5%. NNs for all FPAs were more robust than for CD or acromegaly/mammosomatotroph alone. CONCLUSION We demonstrate capability of predicting suboptimal postoperative outcomes with high accuracy. NNs may aid in stratifying patients for risk of suboptimal outcomes, thereby guiding implementation of adjuvant treatment in high-risk patients.
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Affiliation(s)
- Shane Shahrestani
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
- Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA.
| | - Tyler Cardinal
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Alexander Micko
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
| | - Ben A Strickland
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Dhiraj J Pangal
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Guillaume Kugener
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Martin H Weiss
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - John Carmichael
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Gabriel Zada
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Lines KE, Gluck AK, Thongjuea S, Bountra C, Thakker RV, Gorvin CM. The bromodomain inhibitor JQ1+ reduces calcium-sensing receptor activity in pituitary cell lines. J Mol Endocrinol 2021; 67:83-94. [PMID: 34223822 PMCID: PMC8345903 DOI: 10.1530/jme-21-0030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/05/2021] [Indexed: 12/05/2022]
Abstract
Corticotrophinomas represent 10% of all surgically removed pituitary adenomas, however, current treatment options are often not effective, and there is a need for improved pharmacological treatments. Recently, JQ1+, a bromodomain inhibitor that promotes gene transcription by binding acetylated histone residues and recruiting transcriptional machinery, has been shown to reduce proliferation in a murine corticotroph cell line, AtT20. RNA-Seq analysis of AtT20 cells following treatment with JQ1+ identified the calcium-sensing receptor (CaSR) gene as significantly downregulated, which was subsequently confirmed using real-time PCR and Western blot analysis. CaSR is a G protein-coupled receptor that plays a central role in calcium homeostasis but can elicit non-calcitropic effects in multiple tissues, including the anterior pituitary where it helps regulate hormone secretion. However, in AtT20 cells, CaSR activates a tumour-specific cAMP pathway that promotes ACTH and PTHrP hypersecretion. We hypothesised that the Casr promoter may harbour binding sites for BET proteins, and using chromatin immunoprecipitation (ChIP)-sequencing demonstrated that the BET protein Brd3 binds to the promoter of the Casr gene. Assessment of CaSR signalling showed that JQ1+ significantly reduced Ca2+e-mediated increases in intracellular calcium (Ca2+i) mobilisation and cAMP signalling. However, the CaSR-negative allosteric modulator, NPS-2143, was unable to reduce AtT20 cell proliferation, indicating that reducing CaSR expression rather than activity is likely required to reduce pituitary cell proliferation. Thus, these studies demonstrate that reducing CaSR expression may be a viable option in the treatment of pituitary tumours. Moreover, current strategies to reduce CaSR activity, rather than protein expression for cancer treatments, may be ineffective.
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Affiliation(s)
- Kate E Lines
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford,UK
- Correspondence should be addressed to K E Lines or C M Gorvin: or
| | - Anna K Gluck
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford,UK
| | - Supat Thongjuea
- Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Chas Bountra
- Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Rajesh V Thakker
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford,UK
| | - Caroline M Gorvin
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford,UK
- Institute of Metabolism and Systems Research and Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK
- Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, UK
- Correspondence should be addressed to K E Lines or C M Gorvin: or
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Chen C, Hu Y, Lyu L, Yin S, Yu Y, Jiang S, Zhou P. Incidence, demographics, and survival of patients with primary pituitary tumors: a SEER database study in 2004-2016. Sci Rep 2021; 11:15155. [PMID: 34312470 PMCID: PMC8313564 DOI: 10.1038/s41598-021-94658-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 07/09/2021] [Indexed: 02/05/2023] Open
Abstract
Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan–Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.
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Affiliation(s)
- Cheng Chen
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Yu Hu
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Liang Lyu
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China.,State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Senlin Yin
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Yang Yu
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Shu Jiang
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China.,Pituitary Adenoma Multidisciplinary Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Peizhi Zhou
- Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China. .,Pituitary Adenoma Multidisciplinary Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
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Liu CX, Heng LJ, Han Y, Wang SZ, Yan LF, Yu Y, Ren JL, Wang W, Hu YC, Cui GB. Usefulness of the Texture Signatures Based on Multiparametric MRI in Predicting Growth Hormone Pituitary Adenoma Subtypes. Front Oncol 2021; 11:640375. [PMID: 34307124 PMCID: PMC8294058 DOI: 10.3389/fonc.2021.640375] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 06/16/2021] [Indexed: 01/14/2023] Open
Abstract
Objective To explore the usefulness of texture signatures based on multiparametric magnetic resonance imaging (MRI) in predicting the subtypes of growth hormone (GH) pituitary adenoma (PA). Methods Forty-nine patients with GH-secreting PA confirmed by the pathological analysis were included in this retrospective study. Texture parameters based on T1-, T2-, and contrast-enhanced T1-weighted images (T1C) were extracted and compared for differences between densely granulated (DG) and sparsely granulated (SG) somatotroph adenoma by using two segmentation methods [region of interest 1 (ROI1), excluding the cystic/necrotic portion, and ROI2, containing the whole tumor]. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. Results Among 49 included patients, 24 were DG and 25 were SG adenomas. Nine optimal texture features with significant differences between two groups were obtained from ROI1. Based on the ROC analyses, T1WI signatures from ROI1 achieved the highest diagnostic efficacy with an AUC of 0.918, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.7, 72.0, 100.0, 100.0, and 77.4%, respectively, for differentiating DG from SG. Comparing with the T1WI signature, the T1C signature obtained relatively high efficacy with an AUC of 0.893. When combining the texture features of T1WI and T1C, the radiomics signature also had a good performance in differentiating the two groups with an AUC of 0.908. In addition, the performance got in all the signatures from ROI2 was lower than those in the corresponding signature from ROI1. Conclusion Texture signatures based on MR images may be useful biomarkers to differentiate subtypes of GH-secreting PA patients.
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Affiliation(s)
- Chen-Xi Liu
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.,Functional and Molecular Imaging Key Lab of Shaanxi Province, Xi'an, China
| | - Li-Jun Heng
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China
| | - Yu Han
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China
| | - Sheng-Zhong Wang
- Faculty of Medical Technology, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
| | - Lin-Feng Yan
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.,Functional and Molecular Imaging Key Lab of Shaanxi Province, Xi'an, China
| | - Ying Yu
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.,Functional and Molecular Imaging Key Lab of Shaanxi Province, Xi'an, China
| | | | - Wen Wang
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.,Functional and Molecular Imaging Key Lab of Shaanxi Province, Xi'an, China
| | - Yu-Chuan Hu
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.,Functional and Molecular Imaging Key Lab of Shaanxi Province, Xi'an, China
| | - Guang-Bin Cui
- Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.,Functional and Molecular Imaging Key Lab of Shaanxi Province, Xi'an, China
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Luo M, Tan Y, Chen W, Hu B, Wang Z, Zhu D, Jiao H, Duan C, Zhu Y, Wang H. Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis. Front Neurol 2021; 12:700007. [PMID: 34220696 PMCID: PMC8250148 DOI: 10.3389/fneur.2021.700007] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 05/18/2021] [Indexed: 12/14/2022] Open
Abstract
Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable. Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment. Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007). Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy.
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Affiliation(s)
- Mei Luo
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yiheng Tan
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wenli Chen
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bin Hu
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zongming Wang
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Diming Zhu
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Haosen Jiao
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chengbin Duan
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yonghong Zhu
- Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Haijun Wang
- Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Jaursch-Hancke C, Deutschbein T, Knappe UJ, Saeger W, Flitsch J, Fassnacht M. The Interdisciplinary Management of Newly Diagnosed Pituitary Tumors. DEUTSCHES ARZTEBLATT INTERNATIONAL 2021; 118:237-243. [PMID: 34114552 DOI: 10.3238/arztebl.m2021.0015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 03/31/2020] [Accepted: 09/21/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND The increasing use of cranial tomographic imaging has led to the more frequent discovery of pituitary tumors. In this review, we discuss the clinical symptoms that point toward a pituitary tumor, the required diagnostic studies, the potential need for follow-up studies, and the indications for neurosurgical treatment. METHODS This review is based on pertinent publications from the years 2005-2020 that were retrieved by a selective search in PubMed, as well as on the current German S2k guideline, which was created with the present authors playing a coordinating role, and on further guidelines from abroad. Relevant information from older reviews was also considered. RESULTS The reported prevalence of pituitary tumors varies depending on the method of data acquisition. Autopsy studies yield a figure of 10.7%, while population-based studies reported 77.6-115.6 cases per 100 000 inhabitants. These lesions are nearly always benign, and 85% of them are pituitary adenomas. Pituitary adenomas measuring less than 1 cm in diameter are called microadenomas, while those measuring 1 cm or more are called macroadenomas. According to magnetic resonance imaging (MRI) studies, the prevalence of microadenomas in the general population is in the range of 10-38%, while that of macroadenomas is 0.16-0.3%. Pituitary adenomas can be either hormonally inactive or hormonally active. Half of all patients with hormonally inactive microadenomas display no endocrine abnormality, while 37-85% of patients with hormonally inactive macroadenomas manifest at least partial pituitary insufficiency. The clinical spectrum of pituitary tumors ranges from a fully asymptomatic state to visual disturbances, neurologic deficits, severe hormone excess (e.g., in Cushing disease), and life-threatening pituitary insufficiency. Pituitary adenomas are often diagnosed only after a latency of many years, even when they are symptomatic. If an imaging study shows the tumor to be in contact with the visual pathway, an ophthalmological evaluation should be performed. There are clear indications for surgery, e.g., imminent loss of vision, but most asymptomatic pituitary tumors can be observed only. CONCLUSION The manifestations of pituitary tumors are first recognized by primary care physicians. The further diagnostic evaluation of these patients should be carried out in standardized and interdisciplinary fashion.
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Affiliation(s)
- Cornelia Jaursch-Hancke
- Department of Internal Medicine/Endocrinology, DKD Helios Klinik Wiesbaden Medicover Oldenburg MVZ; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of; Würzburg, Würzburg, Germany; Department of Neurosurgery, Johannes Wesling Klinikum Minden; Institute of Neuropathology, UKE Hamburg; Department of Neurosurgery, UKE Hamburg
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Guo J, Fang Q, Liu Y, Xie W, Zhang Y, Li C. Identifying critical protein-coding genes and long non-coding RNAs in non-functioning pituitary adenoma recurrence. Oncol Lett 2021; 21:264. [PMID: 33664827 PMCID: PMC7882882 DOI: 10.3892/ol.2021.12525] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/17/2020] [Indexed: 12/14/2022] Open
Abstract
Non-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor. Monitoring and predicting the postoperative recurrence of NFPAs is difficult, as these adenomas do not present with serum hormone hypersecretion. Long non-coding RNAs (lncRNAs) and protein-coding genes (PCGs) play critical roles in the development and progression of numerous tumors. However, the complex network of RNA interactions related to the mechanisms underlying the postoperative recurrence of NFPA is still unclear. In the present study, 73 patients with NFPA were investigated using high-throughput sequencing and follow-up investigations. In total, 6 of these patients with recurrence within 1 year after surgery were selected as the fast recurrence group, and 6 patients with recurrence 5 years after surgery were selected as the slow recurrence group. By performing differential expression analysis of the fast recurrence and slow recurrence groups, a set of differentially expressed PCGs and lncRNAs were obtained (t-test, P<0.05). Next, protein-protein interaction coregulatory networks and lncRNA-mRNA coexpression networks were identified. In addition, the hub lncRNA-mRNA modules related to NFPA recurrence were further screened and transcriptome expression markers for NFPA regression were identified (log-rank test, P<0.05). Finally, the ability of the hub and module genes to predict recurrence and progression-free survival in patients with NFPA was evaluated. To confirm the credibility of the bioinformatic analyses, nucleolar protein 6 and LL21NC02-21A1.1 were randomly selected from among the genes with prognostic significance for validation by reverse transcription-quantitative PCR in another set of NFPA samples (n=9). These results may be helpful for evaluating the slow and rapid recurrence of NFPA after surgery and exploring the mechanisms underlying NFPA recurrence. Future effective biomarkers and therapeutic targets may also be revealed.
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Affiliation(s)
- Jing Guo
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China
| | - Qiuyue Fang
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China
| | - Yulou Liu
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China
| | - Weiyan Xie
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China
| | - Yazhuo Zhang
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China.,Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.,Cell laboratory, Beijing Institute for Brain Disorders Brain Tumor Center, Beijing 100070, P.R. China.,Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing 100070, P.R. China
| | - Chuzhong Li
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China.,Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.,Cell laboratory, Beijing Institute for Brain Disorders Brain Tumor Center, Beijing 100070, P.R. China.,Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing 100070, P.R. China
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Ehret F, Kufeld M, Fürweger C, Haidenberger A, Windisch P, Fichte S, Lehrke R, Senger C, Kaul D, Rueß D, Ruge M, Schichor C, Tonn JC, Stalla G, Muacevic A. Robotic Radiosurgery for Persistent Postoperative Acromegaly in Patients with Cavernous Sinus-Invading Pituitary Adenomas-A Multicenter Experience. Cancers (Basel) 2021; 13:cancers13030537. [PMID: 33572555 PMCID: PMC7866786 DOI: 10.3390/cancers13030537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/12/2021] [Accepted: 01/28/2021] [Indexed: 11/25/2022] Open
Abstract
Simple Summary Growth hormone-secreting tumors of the pituitary gland which infiltrate surrounding tissue structures may not be fully resectable. This causes many patients to suffer from acromegaly after an unsuccessful surgery. To limit the considerable morbidity and mortality of such patients, effective and safe treatment options are needed. Fractionated radiotherapy and growth hormone-lowering medication are possible treatment options. Robotic radiosurgery (RRS) may be a suitable treatment modality as well. However, only sparse and heterogeneous data are available. This first retrospective multicenter study investigated the efficacy and safety of RRS for this patient group. Outcomes provide evidence that RRS may achieve biochemical disease control or remission in most of the patients. The hormone levels are decreasing after treatment, whereas favorable risk and safety profiles of RRS were shown. No new tumor growth was observed throughout the available follow-up. These findings may guide future care for this challenging patient population. Abstract Background: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study assesses the efficacy and safety of robotic radiosurgery (RRS) for patients with cavernous sinus-invading adenomas with persistent acromegaly. Methods: Patients who underwent RRS with CyberKnife for postoperative acromegaly were eligible. Results: Fifty patients were included. At a median follow-up of 57 months, the local control was 100%. The pretreatment insulin-like growth factor 1 (IGF-1) levels and indexes were 381 ng/mL and 1.49, respectively. The median dose and prescription isodose were 18 Gy and 70%, respectively. Six months after RRS, and at the last follow-up, the IGF-1 levels and indexes were 277 ng/mL and 1.14, as well as 196 ng/mL and 0.83, respectively (p = 0.0001 and p = 0.0002). The IGF-1 index was a predictor for biochemical remission (p = 0.04). Nine patients achieved biochemical remission and 24 patients showed biochemical disease control. Three patients developed a new hypopituitarism. Conclusions: RRS is an effective treatment for this challenging patient population. IGF-1 levels are decreasing after treatment and most patients experience biochemical disease control or remission.
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Affiliation(s)
- Felix Ehret
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Radiation Oncology, 13353 Berlin, Germany; (C.S.); (D.K.)
- European Cyberknife Center, 81377 Munich, Germany; (M.K.); (C.F.); (A.H.); (P.W.); (A.M.)
- Correspondence:
| | - Markus Kufeld
- European Cyberknife Center, 81377 Munich, Germany; (M.K.); (C.F.); (A.H.); (P.W.); (A.M.)
| | - Christoph Fürweger
- European Cyberknife Center, 81377 Munich, Germany; (M.K.); (C.F.); (A.H.); (P.W.); (A.M.)
| | - Alfred Haidenberger
- European Cyberknife Center, 81377 Munich, Germany; (M.K.); (C.F.); (A.H.); (P.W.); (A.M.)
| | - Paul Windisch
- European Cyberknife Center, 81377 Munich, Germany; (M.K.); (C.F.); (A.H.); (P.W.); (A.M.)
- Department of Radiation Oncology, Kantonsspital Winterthur, 8400 Winterthur, Switzerland
| | - Susanne Fichte
- CyberKnife Center Mitteldeutschland, 99089 Erfurt, Germany;
| | | | - Carolin Senger
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Radiation Oncology, 13353 Berlin, Germany; (C.S.); (D.K.)
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité CyberKnife Center, 13353 Berlin, Germany
| | - David Kaul
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Radiation Oncology, 13353 Berlin, Germany; (C.S.); (D.K.)
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Daniel Rueß
- Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, University Hospital Cologne, 50937 Cologne, Germany; (D.R.); (M.R.)
| | - Maximilian Ruge
- Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, University Hospital Cologne, 50937 Cologne, Germany; (D.R.); (M.R.)
| | - Christian Schichor
- Department of Neurosurgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany; (C.S.); (J.-C.T.)
| | - Jörg-Christian Tonn
- Department of Neurosurgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany; (C.S.); (J.-C.T.)
| | - Günter Stalla
- Medicover Neuroendocrinology, 81667 Munich, Germany;
- Department of Medicine IV, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Alexander Muacevic
- European Cyberknife Center, 81377 Munich, Germany; (M.K.); (C.F.); (A.H.); (P.W.); (A.M.)
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Lehrer EJ, Prabhu AV, Sindhu KK, Lazarev S, Ruiz-Garcia H, Peterson JL, Beltran C, Furutani K, Schlesinger D, Sheehan JP, Trifiletti DM. Proton and Heavy Particle Intracranial Radiosurgery. Biomedicines 2021; 9:31. [PMID: 33401613 PMCID: PMC7823941 DOI: 10.3390/biomedicines9010031] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/23/2020] [Accepted: 12/30/2020] [Indexed: 12/25/2022] Open
Abstract
Stereotactic radiosurgery (SRS) involves the delivery of a highly conformal ablative dose of radiation to both benign and malignant targets. This has traditionally been accomplished in a single fraction; however, fractionated approaches involving five or fewer treatments have been delivered for larger lesions, as well as lesions in close proximity to radiosensitive structures. The clinical utilization of SRS has overwhelmingly involved photon-based sources via dedicated radiosurgery platforms (e.g., Gamma Knife® and Cyberknife®) or specialized linear accelerators. While photon-based methods have been shown to be highly effective, advancements are sought for improved dose precision, treatment duration, and radiobiologic effect, among others, particularly in the setting of repeat irradiation. Particle-based techniques (e.g., protons and carbon ions) may improve many of these shortcomings. Specifically, the presence of a Bragg Peak with particle therapy at target depth allows for marked minimization of distal dose delivery, thus mitigating the risk of toxicity to organs at risk. Carbon ions also exhibit a higher linear energy transfer than photons and protons, allowing for greater relative biological effectiveness. While the data are limited, utilization of proton radiosurgery in the setting of brain metastases has been shown to demonstrate 1-year local control rates >90%, which are comparable to that of photon-based radiosurgery. Prospective studies are needed to further validate the safety and efficacy of this treatment modality. We aim to provide a comprehensive overview of clinical evidence in the use of particle therapy-based radiosurgery.
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Affiliation(s)
- Eric J. Lehrer
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (E.J.L.); (K.K.S.); (S.L.)
| | - Arpan V. Prabhu
- Department of Radiation Oncology, UAMS Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;
| | - Kunal K. Sindhu
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (E.J.L.); (K.K.S.); (S.L.)
| | - Stanislav Lazarev
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (E.J.L.); (K.K.S.); (S.L.)
| | - Henry Ruiz-Garcia
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA; (H.R.-G.); (J.L.P.); (C.B.); (K.F.)
| | - Jennifer L. Peterson
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA; (H.R.-G.); (J.L.P.); (C.B.); (K.F.)
| | - Chris Beltran
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA; (H.R.-G.); (J.L.P.); (C.B.); (K.F.)
| | - Keith Furutani
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA; (H.R.-G.); (J.L.P.); (C.B.); (K.F.)
| | - David Schlesinger
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA 22903, USA; (D.S.); (J.P.S.)
| | - Jason P. Sheehan
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA 22903, USA; (D.S.); (J.P.S.)
| | - Daniel M. Trifiletti
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA; (H.R.-G.); (J.L.P.); (C.B.); (K.F.)
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Wen S, Li J, Yang J, Li B, Li N, Zhan X. Quantitative Acetylomics Revealed Acetylation-Mediated Molecular Pathway Network Changes in Human Nonfunctional Pituitary Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2021; 12:753606. [PMID: 34712204 PMCID: PMC8546192 DOI: 10.3389/fendo.2021.753606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022] Open
Abstract
Acetylation at lysine residue in a protein mediates multiple cellular biological processes, including tumorigenesis. This study aimed to investigate the acetylated protein profile alterations and acetylation-mediated molecular pathway changes in human nonfunctional pituitary neuroendocrine tumors (NF-PitNETs). The anti-acetyl antibody-based label-free quantitative proteomics was used to analyze the acetylomes between NF-PitNETs (n = 4) and control pituitaries (n = 4). A total of 296 acetylated proteins with 517 acetylation sites was identified, and the majority of which were significantly down-acetylated in NF-PitNETs (p<0.05 or only be quantified in NF-PitNETs/controls). These acetylated proteins widely functioned in cellular biological processes and signaling pathways, including metabolism, translation, cell adhesion, and oxidative stress. The randomly selected acetylated phosphoglycerate kinase 1 (PGK1), which is involved in glycolysis and amino acid biosynthesis, was further confirmed with immunoprecipitation and western blot in NF-PitNETs and control pituitaries. Among these acetylated proteins, 15 lysine residues within 14 proteins were down-acetylated and simultaneously up-ubiquitinated in NF-PitNETs to demonstrate a direct competition relationship between acetylation and ubiquitination. Moreover, the potential effect of protein acetylation alterations on NF-PitNETs invasiveness was investigated. Overlapping analysis between acetylomics data in NF-PitNETs and transcriptomics data in invasive NF-PitNETs identified 26 overlapped molecules. These overlapped molecules were mainly involved in metabolism-associated pathways, which means that acetylation-mediated metabolic reprogramming might be the molecular mechanism to affect NF-PitNET invasiveness. This study provided the first acetylomic profiling and acetylation-mediated molecular pathways in human NF-PitNETs, and offered new clues to elucidate the biological functions of protein acetylation in NF-PitNETs and discover novel biomarkers for early diagnosis and targeted therapy of NF-PitNETs.
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Affiliation(s)
- Siqi Wen
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Central South University, Changsha, China
- Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China
| | - Jiajia Li
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Central South University, Changsha, China
- Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China
| | - Jingru Yang
- Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China
| | - Biao Li
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Central South University, Changsha, China
- Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China
| | - Na Li
- Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China
- Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, China
| | - Xianquan Zhan
- Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China
- Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, China
- Gastroenterology Research Institute and Clinical Center, Shandong First Medical University, Jinan, China
- *Correspondence: Xianquan Zhan,
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Chen Y, Gao H, Liu Q, Xie W, Li B, Cheng S, Guo J, Fang Q, Zhu H, Wang Z, Wang J, Li C, Zhang Y. Functional characterization of DLK1/MEG3 locus on chromosome 14q32.2 reveals the differentiation of pituitary neuroendocrine tumors. Aging (Albany NY) 2020; 13:1422-1439. [PMID: 33472171 PMCID: PMC7835058 DOI: 10.18632/aging.202376] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 11/10/2020] [Indexed: 06/12/2023]
Abstract
Pituitary neuroendocrine tumors (PitNETs) represent the neoplastic proliferation of the anterior pituitary gland. Transcription factors play a key role in the differentiation of PitNETs. However, for a substantial proportion of PitNETs, the etiology is poorly understood. According to the transcription data of 172 patients, we found the imprinting disorders of the 14q32.2 region and DLK1/MEG3 locus associated with the differentiation of PitNETs. DLK1/MEG3 locus promoted somatotroph differentiation and inhibited tumor proliferation in PIT1(+) patients, furthermore, the level of DLK1 played a critical role in the trend of somatotroph or lactotroph differentiation. Anti-DLK1 monoclonal antibody blockade or siMEG3 both indicated that the DLK1/MEG3 significantly promoted the synthesis and secretion of GH/IGF-1 and inhibited cell proliferation. In addition, loss of DLK1 activated the mTOR signaling pathway in high DLK1-expressing and PIT1(+) GH3 cell lines, a mild effect in the low DLK1-expressing and PIT1(+) MMQ cell lines and no effect in the PIT1(-) ATT20 cell line. These findings emphasize that expression at the DLK1/MEG3 locus plays a key role in the differentiation of PitNETs, especially somatotroph adenomas, and provide potential molecular target data for patient stratification and treatment in the future.
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Affiliation(s)
- Yiyuan Chen
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Hua Gao
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Qian Liu
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Weiyan Xie
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Bin Li
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Sen Cheng
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Jing Guo
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Qiuyue Fang
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
| | - Haibo Zhu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Zhuang Wang
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Jichao Wang
- Department of Neurosurgery, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang 830001, China
| | - Chuzhong Li
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
- Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing 100070, China
| | - Yazhuo Zhang
- Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
- Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing 100070, China
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Genomic and transcriptomic analysis of pituitary adenomas reveals the impacts of copy number variations on gene expression and clinical prognosis among prolactin-secreting subtype. Aging (Albany NY) 2020; 13:1276-1293. [PMID: 33472173 PMCID: PMC7834992 DOI: 10.18632/aging.202304] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 09/29/2020] [Indexed: 12/16/2022]
Abstract
Pituitary adenomas (PAs) are slow growing and benign primary intracranial tumors that often cause occupying effects or endocrine symptoms. PAs can be classified into various subtypes according to hormone secretion. Although widespread transcriptional alterations that cause aberrant hormone secretion have been characterized, the impact of genomic variations on transcriptional alterations is unclear due to the rare occurrence of single-nucleotide variations in PA. In this study, we performed whole-genome sequencing (WGS) on 76 PA samples across three clinical subtypes (PRL-PAs; GH-PAs, and NFPAs); transcriptome sequencing (RNA-seq) of 54 samples across these subtypes was also conducted. Nine normal pituitary tissues were used as controls. Common and subtype-specific transcriptional alterations in PAs were identified. Strikingly, widespread genomic copy number amplifications were discovered for PRL-PAs, which are causally involved in transcriptomic changes in this subtype. Moreover, we found that the high copy number variations (CNVs) in PRL-PA cause increased prolactin production, drug resistance and proliferative capacity, potentially through key genes with copy number amplification and transcriptional activation, such as BCAT1. This study provides insight into how genomic CNVs affect the transcriptome and clinical outcomes of PRL-PA and sheds light on the development of potential therapeutics for aberrantly activated targets.
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Zhu J, Wang Z, Zhang Y, Li X, Liu J, Deng K, Lu L, Pan H, Wang R, Yao Y, Zhu H. Ectopic pituitary adenomas: clinical features, diagnostic challenges and management. Pituitary 2020; 23:648-664. [PMID: 32757141 DOI: 10.1007/s11102-020-01071-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE Ectopic pituitary adenomas (EPAs) are extremely rare pituitary adenomas located outside the sella turcica without any connection with intrasellar components. This study aims to review all the reported cases to date and describe the clinical characteristics of EPAs. METHODS In a retrospective chart review, 14 patients were identified with EPAs in our hospital. A literature review was performed, and 166 cases in the literature met the criteria. Clinical data were analyzed. RESULTS Of 180 patients with EPAs, the mean age at diagnosis was 45.4 years, and 66.5% of the patients were females. EPAs were mainly located in the sphenoid sinus (34.4%) and suprasellar region (25.6%), followed by the clivus (15.6%), cavernous sinus (13.3%) and nasopharynx (5.6%). Adrenocorticotropic hormone (ACTH)-secreting (38.9%) and nonfunctioning (27.2%) adenomas were predominant. Patients with suprasellar EPAs were more likely to present menstrual disorders and visual changes, while patients with clival EPAs were more likely to suffer from headaches. EPAs in the cavernous sinus and suprasellar space were more likely to be initially misdiagnosed as a suspicious intrasellar mass on imaging examination. The complete tumor resection rates for EPAs in the sphenoid sinus, suprasellar region, clivus, cavernous sinus and nasopharynx were 72.3%, 88.6%, 45.0%, 73.3% and 88.9%, respectively. CONCLUSIONS EPA clinical characteristics varied across different tumor locations and hormone-secreting types. In addition to comprehensive hormone evaluation and careful review of imaging data, nuclear medicine and surgical biopsy should also be considered when facing differential difficulty. EPA management should be individualized.
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Affiliation(s)
- Jianyu Zhu
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Zhicheng Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Yi Zhang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Xiaoxu Li
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Jie Liu
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Lin Lu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Renzhi Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Yong Yao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
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Wang Y, Sun Z, Jiang Z. Cushing's Disease Caused by a Pituitary Microadenoma Coexistent with a Meningioma: A Case Report and Literature Review. Int J Gen Med 2020; 13:1243-1248. [PMID: 33262640 PMCID: PMC7700076 DOI: 10.2147/ijgm.s285833] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/16/2020] [Indexed: 11/23/2022] Open
Abstract
Cushing’s disease (CD), also known as adrenocorticotropic hormone (ACTH)-dependent pituitary Cushing’s syndrome, is a rare and serious chronic endocrine disease that is usually caused by a pituitary adenoma (especially a pituitary microadenoma). Meningioma is the most common type of primary intracranial tumor and is usually benign. The patient in this case report presented with CD coexisting with pituitary microadenoma and meningioma, which is an extremely rare comorbidity. The pathogenesis of CD associated with meningioma remains unclear. Here, we describe the case of bilateral lower extremity edema, lower limb pain, abdominal purplish striae, and abdominal distension for 9 months in a 47-year-old woman. Two years ago, the patient underwent a hysterectomy at a local hospital for hysteromyoma. She had no previous radiotherapeutic treatment or other medical history. Magnetic resonance imaging of her head revealed a sellar lesion (7.8 mm × 6.4 mm) and a spherical mass (3.0 cm × 3.0 cm) in the right frontal convexity. Her level of serum adrenocorticotropic hormone (ACTH) was 169 pg/mL, and her cortisol levels were 933 nmol/mL and 778 nmol/mL at 8 am and 4 pm, respectively. Preoperatively, she was diagnosed with ACTH-secreting pituitary microadenoma and meningioma. Excision of the meningioma was performed through a craniotomy, while an endoscopic endonasal transsphenoidal approach was used to remove the pituitary adenoma. Meningioma and pituitary adenoma were confirmed by postoperative pathology. On the basis of this unusual case, the relevant literature was reviewed to illustrate the diagnosis and treatment of Cushing’s disease and to explore the pathogenesis of pituitary adenoma associated with meningioma.
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Affiliation(s)
- Yu Wang
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Zhixiang Sun
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Zhiquan Jiang
- Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
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Wang Z, Guo X, Gao L, Deng K, Lian W, Bao X, Feng M, Duan L, Zhu H, Xing B. The Immune Profile of Pituitary Adenomas and a Novel Immune Classification for Predicting Immunotherapy Responsiveness. J Clin Endocrinol Metab 2020; 105:5870365. [PMID: 32652004 PMCID: PMC7413599 DOI: 10.1210/clinem/dgaa449] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/08/2020] [Indexed: 02/07/2023]
Abstract
CONTEXT The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness. OBJECTIVE To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune classification for predicting immunotherapy responsiveness. DESIGN, PATIENTS, AND METHODS The transcriptomic data from 259 PAs and 20 normal pituitaries were included for analysis. The ImmuCellAI algorithm was used to estimate the abundance of 24 types of tumor-infiltrating immune cells (TIICs) and the expression of immune checkpoint molecules (ICMs). RESULTS The distributions of TIICs differed between PAs and normal pituitaries and varied among PA subtypes. T cells dominated the immune microenvironment across all subtypes of PAs. The tumor size and patient age were correlated with the TIIC abundance, and the ubiquitin-specific protease 8 (USP8) mutation in corticotroph adenomas influenced the intratumoral TIIC distributions. Three immune clusters were identified across PAs based on the TIIC distributions. Each cluster of PAs showed unique features of ICM expression that were correlated with distinct pathways related to tumor development and progression. CTLA4/CD86 expression was upregulated in cluster 1, whereas programmed cell death protein 1/programmed cell death 1 ligand 2 (PD1/PD-L2) expression was upregulated in cluster 2. Clusters 1 and 2 exhibited a "hot" immune microenvironment and were predicted to exhibit higher immunotherapy responsiveness than cluster 3, which exhibited an overall "cold" immune microenvironment. CONCLUSIONS We summarized the immune profile of PAs and identified 3 novel immune clusters. These findings establish a foundation for further immune studies on PAs and provide new insights into immunotherapy strategies for PAs.
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Affiliation(s)
- Zihao Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Xiaopeng Guo
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Lu Gao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Wei Lian
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Xinjie Bao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Ming Feng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
| | - Lian Duan
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Bing Xing
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
- China Pituitary Disease Registry Center, Beijing, P. R. China
- China Pituitary Adenoma Specialist Council, Beijing, P. R. China
- Correspondence and Reprint Requests: Bing Xing, Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing 100730, P. R. China. E-mail:
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Shi C, Ye Z, Han J, Ye X, Lu W, Ji C, Li Z, Ma Z, Zhang Q, Zhang Y, He W, Chen Z, Cao X, Shou X, Zhou X, Wang Y, Zhang Z, Li Y, Ye H, He M, Chen H, Cheng H, Sun J, Cai J, Huang C, Ye F, Luo C, Zhou B, Ding H, Zhao Y. BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma. Neuro Oncol 2020; 22:1114-1125. [PMID: 32246150 PMCID: PMC7594556 DOI: 10.1093/neuonc/noaa084] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA. METHODS The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes. RESULTS Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bcl2), and related genes, which are vital factors in pituitary tumorigenesis. CONCLUSION In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA.
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Affiliation(s)
- Chengzhang Shi
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zhao Ye
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Jie Han
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Xiaoqing Ye
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Wenchao Lu
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Chenxing Ji
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zizhou Li
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Zengyi Ma
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Qilin Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Yichao Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Wenqiang He
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zhengyuan Chen
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Xiaoyun Cao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Xuefei Shou
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Xiang Zhou
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Yongfei Wang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zhaoyun Zhang
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yiming Li
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hongying Ye
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Min He
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hong Chen
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Pathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Haixia Cheng
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Pathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jun Sun
- Department of Neurosurgery, Central Hospital of Wenzhou, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jianyong Cai
- Department of Neurosurgery, Central Hospital of Wenzhou, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chuanxin Huang
- Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Ye
- College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China
| | - Cheng Luo
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Bing Zhou
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Hong Ding
- Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China
| | - Yao Zhao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Singh R, Didwania P, Lehrer EJ, Sheehan D, Sheehan K, Trifiletti DM, Sheehan JP. Stereotactic radiosurgery for acromegaly: an international systematic review and meta-analysis of clinical outcomes. J Neurooncol 2020; 148:401-418. [PMID: 32506372 DOI: 10.1007/s11060-020-03552-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 05/30/2020] [Indexed: 02/01/2023]
Abstract
INTRODUCTION We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). METHODS Primary outcomes were 5- and 10-year endocrine remission (ER) and endocrine control (EC). Secondary outcomes were 10-year radiographic local control (LC), visual toxicity, and hypopituitarism rates. Weighted random effects meta-analyses using the DerSimonian and Laird methods were conducted to characterize and compare effect sizes. Mixed effects regression models were used to examine correlations between potential prognostic factors and primary and secondary outcomes. RESULTS In total, 1533 patients across 20 published studies with acromegaly treated with SRS were included. At 5-years, estimated ER and EC rates were 43.2% (95% CI 31.7-54.6%) and 55.0% (95% CI 27.6-82.4%), respectively. At 10-years, estimated ER and EC rates were 56.9% (95% CI 47.5-66.4%) and 69.7% (95% CI 47.7-91.8%), respectively. The estimated 10-year LC rate was 92.8% (95% CI 83.0-100%). Visual toxicity and hypopituitarism following SRS were estimated to be 2.7% (95% CI 1.3-4.2%) and 26.8% (95% CI 16.9-36.7%), respectively. Every 1 Gy increase in margin prescription dose beyond 17 Gy was estimated to result in a 0.41% increased risk of visual toxicity (p = 0.03). No prognostic factors were associated with EC, ER, LC, or hypopituitarism. CONCLUSIONS SRS was well-tolerated in the management of pituitary acromegaly resulting in gradually improving ER and EC rates over time that approached 60% and 70%. SRS-related visual loss is an uncommon treatment-related side effect, and patient-specific clinical decision making remains critical.
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Affiliation(s)
- Raj Singh
- Department of Radiation Oncology, Virginia Commonwealth University Health System, Richmond, VA, USA
| | - Prabhanjan Didwania
- Rady School of Management, University of California at San Diego, San Diego, CA, USA
| | - Eric J Lehrer
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Darrah Sheehan
- Department of Neurosurgery, University of Virginia, School of Medicine, Box 800212, Charlottesville, VA, 22903, USA
| | - Kimball Sheehan
- Department of Neurosurgery, University of Virginia, School of Medicine, Box 800212, Charlottesville, VA, 22903, USA
| | | | - Jason P Sheehan
- Department of Neurosurgery, University of Virginia, School of Medicine, Box 800212, Charlottesville, VA, 22903, USA.
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Musha S, Yoshida S, Murakami S, Kojima R, Deai M, Saso N, Mogi C, Sato K, Okajima F, Tomura H. Involvement of GPR4 in increased growth hormone and prolactin expressions by extracellular acidification in MtT/S cells. J Reprod Dev 2020; 66:175-180. [PMID: 31956173 PMCID: PMC7175386 DOI: 10.1262/jrd.2019-159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Hormone-secreting pituitary adenomas show unregulated hormonal hypersecretion and cause hyperpituitarism. However, the mechanism of the unregulated hormone production and secretion has not
yet been fully elucidated. Solid tumors show reduced extracellular pH, partly due to lactate secretion from anaerobic glycolysis. It is known that extracellular acidification affects hormone
secretion. However, whether and how the extracellular acidification influences the unregulated hormone production and secretion remain unknown. In the present study, we found that
GPR4, a proton-sensing G protein-coupled receptor, was highly expressed in MtT/S cells, a growth hormone-producing and prolactin-producing pituitary tumor cell line. When
we reduced the extracellular pH, growth hormone and prolactin mRNA expressions increased in the cells. Both increased expressions were partially suppressed
by a GPR4 antagonist. We also found that extracellular acidification enhanced growth hormone-releasing factor-induced growth hormone secretion from MtT/S cells. These results suggest that
GPR4 may play a role in hypersecretion of the hormone from hormone-producing pituitary tumors. A GPR4 antagonist will be a useful tool for preventing the hypersecretion.
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Affiliation(s)
- Shiori Musha
- Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
| | - Saishu Yoshida
- Department of Biochemistry, Jikei University School of Medicine, Tokyo 105-8461, Japan
| | - Syo Murakami
- Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
| | - Ryotaro Kojima
- Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
| | - Masahito Deai
- Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
| | - Naoshi Saso
- Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
| | - Chihiro Mogi
- Laboratory of Integrated Signaling Systems, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
| | - Koichi Sato
- Laboratory of Medical Neuroscience, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
| | - Fumikazu Okajima
- Laboratory of Pathophysiology, Faculty of Pharmacy, Aomori University, Aomori 030-0943, Japan
| | - Hideaki Tomura
- Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan.,Institute of Endocrinology, Meiji University, Kawasaki 214-8571, Japan
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