Clinical Biology of the Pituitary Adenoma

Endocrine Reviews, Journal Year: 2022, Volume and Issue: 43(6), P. 1003 - 1037

Published: April 8, 2022

Abstract All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between tissues. Pituitary highly prevalent and overwhelmingly benign, exhibiting a spectrum diverse behaviors impact on health. To understand clinical biology common often innocuous neoplasms, we review pituitary physiology adenoma epidemiology, pathophysiology, behavior, consequences. The anterior develops in response range complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland type differentiation, hormonal production, turn maintaining optimal adenomas occur 10% population; however, overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing manifest pathogenic mechanisms disrupt intrapituitary signaling promote benign proliferation associated chromosomal instability. Cellular senescence acts as mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated fewer than one-thousandth all cause clinically significant disease. Adenomas variably adversely affect morbidity mortality depending type, hormone secretory activity, growth behavior. For most apparent adenomas, multimodal therapy controlling secretion lead improved quality life normalized mortality. particularly their nature, stands marked contrast other tumors system, such thyroid neuroendocrine tumors.

Language: Английский

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Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(12), P. 722 - 740

Published: Sept. 5, 2023

Language: Английский

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Cushing syndrome

Nature Reviews Disease Primers, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 23, 2025

Language: Английский

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Flow cytometry immune profiling of recurrent and newly diagnosed growth hormone secreting pituitary neuroendocrine tumors: comparison of two clinical cases

BMC Endocrine Disorders, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 12, 2025

Early detection of aggressive pituitary neuroendocrine tumors (PitNETs) remains challenging due to the absence reliable markers that can predict disease progression. Aggressive are typically identified through long-term observation. Tumor immune microenvironment (TIME) is crucial for understanding PitNETs' heterogeneity and identifying potential predictors tumor aggressiveness. In this study, we analyzed profile micro- macroenvironment in two somatotropinomas (aggressive non-aggressive) using flow cytometry. We observed lymphopenia elevated neutrophil levels periphery patient with recurrence. The TIME showed greater leukocyte infiltration, lymphoid cells predominating over myeloid along a higher proportion CD4 + T CD8 cells. detected double-positive population, high level regulatory sharp increase PD-1 expressing six months during blood recurrence, reduced granule-mediated cytotoxicity NK-cells. number effector producing perforin granzyme B—both independently simultaneously was significantly lower. CD3-CD20- NK CD3-CD56 low after first recurrence but increased sharply months. ratio monocyte subpopulations differed from blood, CD16 monocytes both patients. M2 macrophages rose 60.8% several immunological parameters, exhibited more pronounced immunosuppressive profile.

Language: Английский

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Prognostic Factors for Recurrence in Pituitary Adenomas: Recent Progress and Future Directions

Diagnostics, Journal Year: 2022, Volume and Issue: 12(4), P. 977 - 977

Published: April 13, 2022

Pituitary adenomas (PAs) are benign lesions; nonetheless, some PAs exhibit aggressive behaviors, which lead to recurrence. The impact of pituitary dysfunction, invasion-related risks, and other complications considerably affect the quality life patients with recurrent PAs. Reliable prognostic factors needed for but require confirmation. This review summarizes research progress on two aspects—namely, clinical biological (biomarkers) Postoperative residue, age, immunohistological subtypes, invasion, tumor size, hormone levels, postoperative radiotherapy can predict risk recurrence in Additionally, biomarkers such as Ki-67, p53, cadherin, transforming gene, matrix metalloproteinase-9, epidermal growth factor receptor, fascin actin-bundling protein 1, cyclooxygenase-2, miRNAs lncRNAs may be utilized valuable tools predicting PA As no single marker independently recurrence, we introduce an array comprehensive models grading methods, including multiple factors, prognosis PAs, have shown good effectiveness would beneficial

Language: Английский

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Molecular genetic testing in the management of pituitary disease

Clinical Endocrinology, Journal Year: 2022, Volume and Issue: 97(4), P. 424 - 435

Published: March 29, 2022

Abstract Objective Most pituitary tumours occur sporadically without a genetically identifiable germline abnormality, small but increasing proportion present with genetic defect that predisposes to tumour development, either isolated (e.g., aryl hydrocarbon receptor‐interacting protein, AIP ) or as part of tumour‐predisposing syndrome multiple endocrine neoplasia (MEN) type 1, Carney complex, McCune‐Albright and paraganglioma association). Genetic alterations in sporadic adenomas may include somatic mutations GNAS, USP8 ). In this review, we take practical approach: which syndromes should be considered case different presentation, such type, family history, age onset additional clinical features the patient. Design Review recent literature field genetics tumours. Results testing management disease is recommended significant minority cases. Understanding basis helps identify patients at‐risk members, facilitates early diagnosis therefore better long‐term outcome opens up new pathways leading tumorigenesis. Conclusion We provide concise overview discuss current challenges implications these findings practice.

Language: Английский

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Real-life efficacy and predictors of response to immunotherapy in pituitary tumors: a cohort study

European Journal of Endocrinology, Journal Year: 2022, Volume and Issue: 187(5), P. 685 - 696

Published: Sept. 16, 2022

After temozolomide failure, no evidence-based treatment is available for pituitary carcinomas (PCs) and aggressive tumors (APTs). To date, only 12 cases treated with immune-checkpoint inhibitors (ICIs) have been published, showing encouraging efficacy. Predictive factors of response are lacking. Here, we aimed to assess the real-life efficacy predictors ICIs in PCs APTs.This study a multicentric, retrospective, observational cohort study, including all APTs France up March 2022. PD-L1 immunohistochemistry CD8+ T cell infiltration were evaluated centrally.Six (four corticotroph two lactotroph) nine (five four included. The was lower than previously published data. Three (33.3%) showed partial response, one (11.1%) stable disease, while five (55.6%) progressed. One lactotroph tumor (16.7%) (66.7%) responded far better APTs, 4/6 compared 0/9 APTs. Corticotroph slightly tumors. In responsive tumors, staining negative attained maximum 1% center.Confirmation presence or absence metastases necessary before starting ICIs. appear as good therapeutic option PCs, especially carcinomas. Negative very low center should not preclude ICI administration carcinomas.This first We also assessed potential predictive value infiltration. identified type major predictor, proving more effective treating PCs. Our provides evidence that after failure six responded), (three responded). provide Moreover, our findings point toward need systematically perform extension workup

Language: Английский

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Prolactin-secreting pituitary adenomas: male-specific differences in pathogenesis, clinical presentation and treatment

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 2, 2024

Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and one-fifth them are diagnosed in males. The clinical presentation PRLomas results from direct prolactin (PRL) action, duration severity hyperprolactinemia, tumor mass effect. Male PRLomas, compared to females, tend be larger more invasive, associated with higher PRL concentration at diagnosis, present proliferative potential, frequently resistant standard pharmacotherapy, thus may require multimodal approach, including surgical resection, radiotherapy, alternative medical agents. Therefore, the management men is challenging many cases. Additionally, hyperprolactinemia a significant negative impact on men’s health, sexual function fertility bone cardiovascular metabolic complications, leading decreased quality life. In this review, we highlight differences pathogenesis, treatment concerning male sex.

Language: Английский

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Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: April 24, 2024

Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, precise immunological environment and its control over tumor poorly understood. The heterogeneity, spatial distribution, clinical significance macrophages were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, transcriptomics, immunohistochemistry, multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences process apoptosis. present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. objective was to explore diversity composition across these Analyzed 365 conducted in-house revealed presence three unique subtypes microenvironment (TIME) PitNETs. These characterized by varying levels infiltration, ranging low intermediate high. In addition, NR5A1 lineage is primarily associated with subtype limited infiltration cells. Tumor-associated (TAMs) expressing CX3CR1+, C1Q+, GPNMB+ showed enhanced contact + , TBX19+, POU1F1+, respectively. This emphasizes distinct interaction axes between TAMs based on their lineage. Moreover, connection CX3CR1+ via regulates summary, different TIME TAM offer valuable insights affects development PitNET. findings can be utilized as prospective targets for therapeutic interventions.

Language: Английский

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Real-life clinical impact of a five-tiered classification of pituitary tumors

European Journal of Endocrinology, Journal Year: 2022, Volume and Issue: 187(6), P. 893 - 904

Published: Oct. 31, 2022

Usually benign, pituitary tumors (PT) can be invasive and aggressive with a propensity to progress and/or recur. Trouillas's clinicopathological classification attempts predict the evolutionary risk of PT. In this study, we assessed prognostic value in an independent patient cohort analyzed its impact on treatment strategies.In 607 patients operated between 2008 2018 for PT were included. Grading was established based invasion, proliferative activity (Ki-67, mitotic index) p53 positivity. The therapeutic management following surgery analyzed. Progression-free survival (PFS) graded estimated (Kaplan-Meier method log-rank test) multivariate analysis performed (Cox regression model).Grading identified non-invasive without (grade 1a: 303 cases) or 1b: 53 2a: 202 2b: 49 cases). mean follow-up 47 ± 30 months (median: 38 months). Progression/recurrence occurred 127 cases. Grades significant predictors PFS (P < 0.001) 4.8-fold higher progression/recurrence grade 2b as compared 1a. As second-line therapy, gamma knife conventional radiotherapy controlled tumor growth 91.6 100% cases, respectively, irrespective grade. Proliferative exposed 9.5-fold having ≥3 adjuvant lines non-proliferative tumors.Grading according predicts progression should advocate personalized approach tumors.This is first study assess, well-characterized patients, real-life five-tiered tumors. First, validate that grades tumor, (mean follow-up: months, median: Moreover, our provides evidence have retreated after primary point toward fact successfully control case recurrence. Our findings clinically

Language: Английский

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