MICROSURGICAL ANATOMY OF THE DIAPHRAGMA SELLAE AND ITS ROLE IN DIRECTING THE PATTERN OF GROWTH OF PITUITARY ADENOMAS

Abstract OBJECTIVE To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma. METHODS Twenty cadaveric heads were dissected and measurements were taken at the level of the diaphragma sellae. RESULTS The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4–10.7 mm) and the average lateral-to-lateral distance was 7.33 mm (range, 2.8–14.1 mm). CONCLUSION The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.

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Advances in Our Understanding of Pituitary Adenoma

US Endocrinology ◽

10.17925/use.2008.04.01.88 ◽

2008 ◽

Vol 04 (01) ◽

pp. 88

Author(s):

Sandra Pekic ◽

Vera Popovic-Brkic

Keyword(s):

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Pituitary Tumors ◽

Pituitary Hormones ◽

Current Treatment ◽

Thyroid Stimulating Hormone ◽

Treatment Modalities ◽

High Resolution Computed Tomography ◽

New Therapeutic Approaches ◽

Asymptomatic Patients

Pituitary adenomas are common benign monoclonal neoplasms— accounting for 15% of intracranial neoplasms—that may be clinically silent or secrete anterior pituitary hormones such as prolactin, growth hormone (GH), adrenocorticotrophic hormone (ACTH), or, rarely, thyroid-stimulating hormone (TSH) or gonadotrophins. Radiological studies for other reasons using high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) detect incidental pituitary adenomas in approximately 20% of asymptomatic patients.1The incidence of the various types of adenoma varies;2prolactinomas are the most common pituitary adenomas. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones, often cause local mass symptoms and represent one-third of pituitary adenomas. GH- and ACTH-producing adenomas each account for 10–15% of pituitary adenomas, while TSH-producing adenomas are rare. Pituitary adenomas are infrequent in childhood: fewer than 10% of pituitary adenomas are diagnosed before 20 years of age.3These adenomas can be either microor macroadenomas. The natural course of microadenomas is that a few tumors enlarge over a period of more than eight years.Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, our understanding of pituitary tumorigenesis remains incomplete and is the focus of current research. The reason for this is that current treatment modalities fail to completely control this disorder and prevent the associated morbidity and mortality. This article reviews the advances in our understanding of pituitary adenoma, especially in the field of pathogenesis of pituitary tumors, and the possibility of new therapeutic approaches.

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Genomic and molecular characterization of pituitary adenoma pathogenesis: review and translational opportunities

Neurosurgical FOCUS ◽

10.3171/2020.3.focus20104 ◽

2020 ◽

Vol 48 (6) ◽

pp. E11 ◽

Cited By ~ 1

Author(s):

Mazin Elsarrag ◽

Parantap D. Patel ◽

Ajay Chatrath ◽

Davis Taylor ◽

John A. Jane

Keyword(s):

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Basic Science ◽

Cell Cycle Progression ◽

Regulation Of Gene Expression ◽

Gene Mutations ◽

Pituitary Tumors ◽

Rational Drug Design ◽

Therapeutic Interventions ◽

Neoplastic Disease

OBJECTIVEInnovations in genomics, epigenomics, and transcriptomics now lay the groundwork for therapeutic interventions against neoplastic disease. In the past 30 years, the molecular pathogenesis of pituitary adenomas has been characterized. This enhanced understanding of the biology of pituitary tumors has potential to impact current treatment paradigms, and there exists significant translational potential for these results. In this review the authors summarize the results of genomics and molecular biology investigations into pituitary adenoma pathogenesis and behavior and discuss opportunities to translate basic science findings into clinical benefit.METHODSThe authors searched the PubMed and MEDLINE databases by using combinations of the keywords “pituitary adenoma,” “genomics,” “pathogenesis,” and “epigenomics.” From the initial search, additional articles were individually evaluated and selected.RESULTSPituitary adenoma growth is primarily driven by unrestrained cell cycle progression, deregulation of growth and proliferation pathways, and abnormal epigenetic regulation of gene expression. These pathways may be amenable to therapeutic intervention. A significant number of studies have attempted to establish links between gene mutations and tumor progression, but a thorough mechanistic understanding remains elusive.CONCLUSIONSAlthough not currently a prominent aspect in the clinical management of pituitary adenomas, genomics and epigenomic studies may become essential in refining patient care and developing novel pharmacological agents. Future basic science investigations should aim at elucidating mechanistic understandings unique to each pituitary adenoma subtype, which will facilitate rational drug design.

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Pituitary Adenomas Associated with Intracranial Aneurysms – The Clinical Characteristics, Therapeutic Strategies, and Possible Effects of Vascular Remodeling Factors

10.21203/rs.3.rs-80983/v1 ◽

2020 ◽

Author(s):

Yoshikazu Ogawa ◽

Mika Watanabe ◽

Teiji Tominaga

Keyword(s):

Pituitary Adenoma ◽

Cavernous Sinus ◽

Pituitary Adenomas ◽

Vascular Remodeling ◽

Intracranial Aneurysms ◽

Clinical Characteristics ◽

Cerebral Aneurysms ◽

Therapeutic Strategies ◽

Cavernous Sinus Invasion ◽

Endothelial Growth Factor

Abstract Objective: Pituitary adenoma coexists with intracranial aneurysms in 2.3% to 3.6%, and intracranial aneurysms is thought to be incidental. On the other hand higher age and cavernous sinus invasion are reported to increase the coexistence rate, so these two diseases may be related. Ten males and 14 females with coexistence of pituitary adenomas and intracranial aneurysms were retrospectively investigated among 923 patients (2.6%). Patients were subdivided into two groups with/without direct attachment of cerebral aneurysms to the pituitary adenomas. The clinical characteristics, therapeutic strategies, and possible effects of vascular remodeling factors were investigated.Results: Twelve patients had functioning pituitary adenomas, and cavernous sinus invasion was identified in 7 of 24 patients. Five of these 7 patients were treated with priority for the cerebral aneurysms until 2007, whereas 14 of 17 patients without involvement of the aneurysm tip in the tumor were treated with priority for pituitary adenomas in the later period. Among vascular remodeling factors strong expression of vascular endothelial growth factor (VEGF) was significantly associated with coexistence of pituitary adenoma and cerebral aneurysm (p < 0.05). So VEGF-induced arterial wall remodeling may be part of the mechanism of association between pituitary adenomas and cerebral aneurysms, suggesting possible causative mechanism.

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Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant

Scientific Reports ◽

10.1038/s41598-021-95829-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cheol Ryong Ku ◽

Hyeonseob Lim ◽

Yang Jong Lee ◽

Sun Ho Kim ◽

Daham Kim ◽

...

Keyword(s):

Growth Hormone ◽

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Pituitary Tumors ◽

Genetic Alterations ◽

Biochemical Activity ◽

Recurrent Point ◽

Targeted Resequencing ◽

Severance Hospital

AbstractWe aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.

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Up-regulation of sex-determining region Y-box 9 (SOX9) in growth hormone-secreting pituitary adenomas

BMC Endocrine Disorders ◽

10.1186/s12902-021-00720-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Farzad Izak Shirian ◽

Mohammad Ghorbani ◽

Mohammad E. Khamseh ◽

Mehrnaz Imani ◽

Mahshid Panahi ◽

...

Keyword(s):

Pituitary Adenoma ◽

Expression Pattern ◽

Protein Level ◽

Pituitary Adenomas ◽

Pituitary Tumors ◽

Expression Level ◽

Sox9 Expression ◽

Over Expression ◽

Tumor Tissues ◽

Sox9 Gene

Abstract Background Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated. Methods The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient’s clinical and pathological features were considered. Results The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors. Conclusion The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.

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Reformatted Sagittal Images in the Differential Diagnosis of Meningiomas and Pituitary Adenomas with Suprasellar Extension

Neurosurgery ◽

10.1227/00006123-198605000-00007 ◽

1986 ◽

Vol 18 (5) ◽

pp. 555-558 ◽

Cited By ~ 8

Author(s):

Craig W. Clark ◽

James D. Acker ◽

Jon H. Robertson ◽

Frank Eggers ◽

Michael S. Muhlbauer

Keyword(s):

Computed Tomography ◽

Differential Diagnosis ◽

Pituitary Adenoma ◽

High Resolution ◽

Pituitary Adenomas ◽

Pituitary Tumors ◽

Suprasellar Extension

Abstract Approximately 3 to 4 times a year, a tumor with suprasellar extension escapes classification on high resolution coronal and transaxial computed tomography. When arteriography failed to determine the diagnosis, the differential choices were usually meningioma or pituitary adenoma. The authors report the use of sagittal reformatted images in this differential diagnosis and conclude that these images may aid in the distinction between pituitary tumors with suprasellar extension and meningiomas located in this area.

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Magmas, a Gene Newly Identified as Overexpressed in Human and Mouse ACTH-Secreting Pituitary Adenomas, Protects Pituitary Cells from Apoptotic Stimuli

Endocrinology ◽

10.1210/en.2010-0441 ◽

2010 ◽

Vol 151 (10) ◽

pp. 4635-4642 ◽

Cited By ~ 23

Author(s):

Federico Tagliati ◽

Erica Gentilin ◽

Mattia Buratto ◽

Daniela Molè ◽

Ettore Ciro degli Uberti ◽

...

Keyword(s):

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Mitochondrial Protein ◽

Pituitary Tumors ◽

Pituitary Cells ◽

Subcellular Compartment ◽

Adenoma Cell ◽

Macrophage Colony ◽

Reduced Rate ◽

Acth Secreting

Pituitary tumors are mostly benign, being locally invasive in 5–35% of cases. Deregulation of several genes has been suggested as a possible alteration underlying the development and progression of pituitary tumors. We here report the identification of a cDNA, corresponding to Magmas gene (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction), which is highly expressed in two different ACTH-secreting mouse pituitary adenoma cell lines as compared with normal pituitary as well as in two thirds of 64 examined pituitary adenomas as compared with human normal pituitary. Tim 16, the mitochondrial protein encoded by Magmas, was indeed expressed in a mouse ACTH-secreting pituitary adenoma cell line, AtT-20 D16v-F2 cells, in a subcellular compartment likely corresponding to mitochondria. Magmas silencing determined a reduced rate of DNA synthesis, an accumulation in G1 phase, and a concomitant decrease in S phase in At-T20 D16v-F2 cells. Moreover, Magmas-silenced cells displayed basal caspase 3/7 activity and DNA fragmentation levels similar to control cells, which both increased under proapoptotic stimuli. Our data demonstrate that Magmas is overexpressed in mouse and human ACTH-secreting pituitary adenomas. Moreover, our results show that Magmas protects pituitary cells from apoptosis, suggesting its possible involvement in neoplastic transformation.

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Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

Endocrine Reviews ◽

10.1210/er.2012-1013 ◽

2013 ◽

Vol 34 (2) ◽

pp. 239-277 ◽

Cited By ~ 188

Author(s):

Albert Beckers ◽

Lauri A. Aaltonen ◽

Adrian F. Daly ◽

Auli Karhu

Keyword(s):

Pituitary Adenoma ◽

Aryl Hydrocarbon Receptor ◽

Pituitary Adenomas ◽

Pituitary Tumors ◽

Carney Complex ◽

Cushing Disease ◽

Interacting Protein ◽

Aryl Hydrocarbon ◽

Serious Disease ◽

Aip Gene

Abstract Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses the current clinical and therapeutic characteristics of more than 200 FIPA families and addresses research findings among AIP mutation-bearing patients in different populations with pituitary adenomas.

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Management of Aggressive Pituitary Tumors – A 2019 Update

Hormone and Metabolic Research ◽

10.1055/a-1060-1883 ◽

2019 ◽

Vol 51 (12) ◽

pp. 755-764 ◽

Cited By ~ 2

Author(s):

Stephan Petersenn

Keyword(s):

Pituitary Adenoma ◽

Treatment Failure ◽

Pituitary Adenomas ◽

Pituitary Tumors ◽

Therapeutic Management ◽

Second Line ◽

Radiation Oncologist ◽

Limited Data ◽

Special Challenge

AbstractWith a prevalence of 80–100/100000, pituitary adenomas are more frequent than thought. The rare aggressive pituitary adenoma presents a special challenge, due to the heterogenous presentation of the disease. The prognosis of aggressive pituitary adenomas has been improved due to recent studies demonstrating some efficacy of chemotherapy with temozolomide. However, there is very limited data on second-line therapies in patients with treatment failure. This review presents an update on the diagnostic and therapeutic management of aggressive pituitary tumors. Patients should be treated by a team consisting of an expert endocrinologist, neurosurgeon, radiation oncologist, and pathologist, and according to the recently published ESE guideline.

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IL-18 expression in clinical human pituitary adenoma

Technology and Health Care ◽

10.3233/thc-191967 ◽

2021 ◽

pp. 1-6

Author(s):

Qi Shao ◽

Ning Liu ◽

Guo-Fu Li ◽

Qian-Cheng Meng ◽

Jia-Hao Yao ◽

...

Keyword(s):

Pituitary Adenoma ◽

Mrna Expression ◽

Pituitary Adenomas ◽

Adrenocorticotropic Hormone ◽

Pituitary Tumors ◽

Thyroid Stimulating Hormone ◽

Mrna Levels ◽

Human Pituitary ◽

Human Pituitary Adenoma ◽

Real Time Quantitative Pcr

BACKGROUND: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein. OBJECTIVE: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas. METHODS: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR. RESULTS: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas. CONCLUSIONS: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

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