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CNS Neuroscience & Therapeutics Oct 2023Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign... (Review)
Review
Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress-regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 37341156
DOI: 10.1111/cns.14315 -
Operative Neurosurgery (Hagerstown, Md.) Jan 2024The management of giant pituitary adenomas (GPAs) is challenging due to associated endocrinopathies and the close proximity of these tumors to critical structures, such... (Review)
Review
BACKGROUND AND OBJECTIVES
The management of giant pituitary adenomas (GPAs) is challenging due to associated endocrinopathies and the close proximity of these tumors to critical structures, such as the optic nerves, structures of the cavernous sinus, and hypothalamus. The objective of this review article was to summarize the current management strategies for giant pituitary adenomas, including the role of open and endoscopic surgical approaches and the role of medical and radiation therapy in conjunction with surgery.
METHODS
We conducted a retrospective review of GPAs operated at our institute between January 2010 and March 2023. Surgical approaches, extent of resection, and associated complications were documented. Furthermore, we conducted a thorough literature review to identify relevant studies published in the past decade, which were incorporated along with insights gained from our institutional case series of GPAs to analyze and integrate both the existing knowledge base and our institution's firsthand experience in the management of GPAs.
RESULTS
A total of 46 giant pituitary adenomas (GPAs) were operated on, using various surgical approaches. Transsphenoidal approach was used in 25 cases and a staged approach using transsphenoidal and pterional was used in 15 cases. Other approaches included transcortical-transventricular, transcallosal, pterional/orbitozygomatic, and subfrontal approaches. Complications and technical nuances were reported.
CONCLUSION
The management of giant pituitary adenomas remains complex, often involving several modalities-open or endoscopic resection, radiosurgery, and medical management of both the tumor and associated endocrinopathies. Surgical resections are often challenging procedures that require careful consideration of several factors, including patient characteristics, tumor location, and size, and the experience and skill of the surgical team.
Topics: Humans; Pituitary Neoplasms; Treatment Outcome; Magnetic Resonance Imaging; Adenoma; Endoscopy
PubMed: 37655871
DOI: 10.1227/ons.0000000000000896 -
Frontiers in Endocrinology 2023The invasive behavior of nonfunctioning pituitary neuroendocrine tumors (NF-PitNEts) affects complete resection and indicates a poor prognosis. Cancer immunotherapy has...
INTRODUCTION
The invasive behavior of nonfunctioning pituitary neuroendocrine tumors (NF-PitNEts) affects complete resection and indicates a poor prognosis. Cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The current study aimed to screen the key immune-related genes in NF-PitNEts with invasion.
METHODS
We used two cohorts to explore novel biomarkers in NF-PitNEts. The immune infiltration-associated differentially expressed genes (DEGs) were obtained based on high/low immune scores, which were calculated through the ESTIMATE algorithm. The abundance of immune cells was predicted using the ImmuCellAI database. WGCNA was used to construct a coexpression network of immune cell-related genes. Random forest analysis was used to select the candidate genes associated with invasion. The expression of key genes was verified in external validation set using quantitative real-time polymerase chain reaction (qRT‒PCR).
RESULTS
The immune and invasion related DEGs was obtained based on the first dataset of NF-PitNEts (n=112). The immune cell-associated modules in NF-PitNEts were calculate by WGCNA. Random forest analysis was performed on 81 common genes intersected by immune-related genes, invasion-related genes, and module genes. Then, 20 of these genes with the highest RF score were selected to construct the invasion and immune-associated classification model. We found that this model had high prediction accuracy for tumor invasion, which had the largest area under the receiver operating characteristic curve (AUC) value in the training dataset from the first dataset (n=78), the self-test dataset from the first dataset (n=34), and the independent test dataset (n=73) (AUC=0.732/0.653/0.619). Functional enrichment analysis revealed that 8 out of the 20 genes were enriched in multiple signaling pathways. Subsequently, the 8-gene (BMP6, CIB2, FABP5, HOMER2, MAML3, NIN, PRKG2 and SIDT2) classification model was constructed and showed good efficiency in the first dataset (AUC=0.671). In addition, the expression levels of these 8 genes were verified by qRT‒PCR.
CONCLUSION
We identified eight key genes associated with invasion and immunity in NF-PitNEts that may play a fundamental role in invasive progression and may provide novel potential immunotherapy targets for NF-PitNEts.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Pituitary Diseases; Neoplastic Processes; Biomarkers; Tumor Microenvironment; Fatty Acid-Binding Proteins; Nucleotide Transport Proteins
PubMed: 37522128
DOI: 10.3389/fendo.2023.1131693 -
The Neuroradiology Journal Feb 2024Intracranial xanthogranulomas (XGs) have been found at various sites, but xanthogranuloma of the sellar region is extremely rare. We report about a case of sellar XG in...
Intracranial xanthogranulomas (XGs) have been found at various sites, but xanthogranuloma of the sellar region is extremely rare. We report about a case of sellar XG in a 34-year-old female. Magnetic resonance imaging showed a solid-cystic mass located at the sella turcica. The cystic component was hyperintense on the T1-weighted image (WI) and T2WI. The solid component was hyperintense on T1WI and hypointense on T2WI. There was peripheral enhancement after gadolinium administration. The diagnosis of cystic macroadenoma was considered before surgery. Final diagnosis of XG was confirmed by histopathological examination after surgical resection. Gross total resection of the lesion was achieved using the microscope through endoscopic endonasal transsphenoidal approach. The patient had a good outcome and no symptom of diabetes insipidus, hormonal evaluation did not show any alterations compatible with hypopituitarism and prolactin levels were normal XG should receive diagnostic consideration for the sellar mass lesions with cystic components hyperintense on T1WI and T2WI, solid components hyperintense on T1WI and hypointense on T2WI, and CT without evidence of calcifications. It is important to consider the possibility of XG when pertinent, as it facilitates a proper surgical approach strategy.
Topics: Female; Humans; Adult; Magnetic Resonance Imaging; Sella Turcica; Endoscopy; Granuloma; Xanthomatosis; Pituitary Neoplasms
PubMed: 36951613
DOI: 10.1177/19714009231166075 -
Neurosurgical Focus Aug 2023The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis).
OBJECTIVE
The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis).
METHODS
The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected.
RESULTS
The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months).
CONCLUSIONS
Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.
Topics: Male; Humans; Female; Aged; Retrospective Studies; Treatment Outcome; Pituitary Gland; Pituitary Neoplasms; Hypopituitarism; Headache
PubMed: 37527679
DOI: 10.3171/2023.5.FOCUS23185 -
The Pan African Medical Journal 2023Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1)....
Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). This is a retrospective study of patients who were hospitalized in the Endocrinology Department of the Mohammed V Military Academic Hospital in Rabat over a period of 14 years (2008 to 2022), reporting on their clinical, paraclinical and evolutionary profiles and comparing the results with the data in the literature. Nineteen patients were included in our study. The mean age was 42.7 ± 11.6 years, with a male predominance. The clinical manifestations were dominated by a dysmorphic syndrome present in 97.4% of cases, followed by complications related to acromegaly in 88.9% of cases. The diagnosis was made when GH and IGF-1 values were elevated in 88.9% and 93.8% of cases, respectively; with a mean GH value of 25.1 μg/L. Magnetic resonance imaging (MRI) was used to diagnose the location of pituitary adenoma in all cases, 78.9% of which were macroadenomas and 21.1% microadenomas. The majority of patients (78.9%) had recourse to transsphenoidal surgery. Medical treatment was carried out in 89.5% of cases. Postoperative radiotherapy was performed in 33% of cases. Disease control was achieved in 30.1% of cases. This study shows the complex management of acromegaly. Disease control is a necessary condition in order to avoid complications, but is often difficult to obtain.
Topics: Humans; Male; Adult; Middle Aged; Female; Acromegaly; Insulin-Like Growth Factor I; Retrospective Studies; Treatment Outcome; Human Growth Hormone; Pituitary Neoplasms
PubMed: 38465009
DOI: 10.11604/pamj.2023.46.116.41952 -
European Journal of Endocrinology Sep 2023A somatic mutational hotspot in the SF3B1 gene was reported in lactotroph tumours. The aim of our study was to examine the prevalence of driver SF3B1 variants in a...
OBJECTIVE
A somatic mutational hotspot in the SF3B1 gene was reported in lactotroph tumours. The aim of our study was to examine the prevalence of driver SF3B1 variants in a multicentre independent cohort of patients with lactotroph tumours and correlate with clinical data.
DESIGN AND METHODS
This was a retrospective, multicentre study involving 282 patients with lactotroph tumours (including 6 metastatic lactotroph tumours) from 8 European centres. We screened SF3B1 exon 14 hotspot for somatic variants using Sanger sequencing and correlated with clinicopathological data.
RESULTS
We detected SF3B1 variants in seven patients with lactotroph tumours: c.1874G > A (p.Arg625His) (n = 4, 3 of which metastatic) and a previously undescribed in pituitary tumours variant c.1873C > T (p.Arg625Cys) (n = 3 aggressive pituitary tumours). In two metastatic lactotroph tumours with tissue available, the variant was detected in both primary tumour and metastasis. The overall prevalence of likely pathogenic SF3B1 variants in lactotroph tumours was 2.5%, but when we considered only metastatic cases, it reached the 50%. SF3B1 variants correlated with significantly larger tumour size; higher Ki67 proliferation index; multiple treatments, including radiotherapy and chemotherapy; increased disease-specific death; and shorter postoperative survival.
CONCLUSIONS
SF3B1 variants are uncommon in lactotroph tumours but may be frequent in metastatic lactotroph tumours. When present, they associate with aggressive tumour behaviour and worse clinical outcome.
Topics: Humans; Pituitary Neoplasms; Lactotrophs; Prevalence; Retrospective Studies; Transcription Factors; RNA Splicing Factors; Phosphoproteins
PubMed: 37721395
DOI: 10.1093/ejendo/lvad114 -
Frontiers in Endocrinology 2023Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of small-sized and medium (<30 mm) somatotropinoma removal and the incidence of postoperative complications in patients with acromegaly when using microscopic and endoscopic techniques.
METHODS
In this randomized controlled trial, a total of 83 patients with acromegaly underwent transspheroidal endoscopy or microscopic surgery. Somatotropinoma was the cause of acromegaly in all cases. Patients were randomly divided into two comparison groups depending on the applied surgical technique. Group 1 (n = 40) consisted of patients who underwent adenomectomy with transnasal transsphenoidal access by a microscope. Group 2 (n = 43) included patients who underwent the same surgical procedure with an endoscope. The following indicators were assessed: radicality of tumor removal, treatment effectiveness, postoperative complications, and remission rate.
RESULTS
The study has shown that removal of somatotropinoma in patients with acromegaly using endoscopic technique increases the radicality of tumor removal in comparison with microscopic technique. Total removal of somatotropinoma was successful in 88.4% of cases when using the endoscopic technique. Secondly, the segmentation of patients according to their tumor characteristics poses challenges, primarily owing to the rarity of acromegaly as a disease. The difference between groups was not statistically significant (p=1.02). There were no statistically significant differences in basal GH level and IGF-1 level between groups (p=0.546 and p=0.784, respectively).
DISCUSSION
Endonasal transsphenoidal endoscopic adenomectomy is proven efficacy, a less traumatic degree, and higher somatotropinoma removal radicality. Both surgical methods lead to disease remission.
Topics: Humans; Acromegaly; Endoscopy; Adenoma; Growth Hormone-Secreting Pituitary Adenoma; Postoperative Complications; Pituitary Neoplasms
PubMed: 37766690
DOI: 10.3389/fendo.2023.1128345 -
Nature Reviews. Endocrinology May 2024Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management... (Review)
Review
Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.
Topics: Adult; Male; Female; Humans; Adolescent; Child; Aged; Pituitary Neoplasms; Adenoma; Acromegaly; Prolactinoma
PubMed: 38336898
DOI: 10.1038/s41574-023-00949-7 -
Operative Neurosurgery (Hagerstown, Md.) Oct 2023Surgical access to the cavernous sinus (CS) poses a unique challenge to the neurosurgeon given the concentration of delicate structures in the confines of a very small...
BACKGROUND AND OBJECTIVES
Surgical access to the cavernous sinus (CS) poses a unique challenge to the neurosurgeon given the concentration of delicate structures in the confines of a very small anatomic space. The lateral transorbital approach (LTOA) is a minimally invasive, keyhole approach that can provide direct access to the lateral CS.
METHODS
A retrospective review of CS lesions treated by a LTOA at a single institution was performed between 2020 and 2023. Patient indications, surgical outcomes, and complications are described.
RESULTS
Six patients underwent a LTOA for a variety of pathologies including a dermoid cyst, schwannoma, prolactinoma, craniopharyngioma, and solitary fibrous tumor. The goals of surgery (ie, drainage of cyst, debulking, and pathological diagnosis) were achieved in all cases. The mean extent of resection was 64.6% (±34%). Half of the patients with preoperative cranial neuropathies (n = 4) improved postoperatively. There were no new permanent cranial neuropathies. One patient had a vascular injury repaired endovascularly with no neurological deficits.
CONCLUSION
The LTOA provides a minimal access corridor to the lateral CS. Careful case selection and reasonable goals of surgery are critical to successful outcome.
Topics: Humans; Cavernous Sinus; Cranial Nerve Diseases; Craniopharyngioma; Retrospective Studies; Pituitary Neoplasms
PubMed: 37427936
DOI: 10.1227/ons.0000000000000824