Molecular genetic testing in the management of pituitary disease DOI Open Access
Eva C Coopmans, Márta Korbonits

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

Consensus on diagnosis and management of Cushing's disease: a guideline update DOI Creative Commons
Maria Fleseriu, Richard J. Auchus, Irina Bancos

et al.

The Lancet Diabetes & Endocrinology, Journal Year: 2021, Volume and Issue: 9(12), P. 847 - 875

Published: Oct. 22, 2021

Language: Английский

Citations

254
Clinical Biology of the Pituitary Adenoma DOI Creative Commons
Шломо Мелмед, Ursula B. Kaiser, M. Beatriz S. Lopes

et al.

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

Citations

172
Acromegaly: pathogenesis, diagnosis, and management DOI
Maria Fleseriu, Fabienne Langlois, Dawn Shao Ting Lim

et al.

The Lancet Diabetes & Endocrinology, Journal Year: 2022, Volume and Issue: 10(11), P. 804 - 826

Published: Oct. 6, 2022

Language: Английский

Citations

133
Aggressive pituitary tumours and pituitary carcinomas DOI
Gérald Raverot, Mirela Diana Ilie, Hélène Lasolle

et al.

Nature Reviews Endocrinology, Journal Year: 2021, Volume and Issue: 17(11), P. 671 - 684

Published: Sept. 7, 2021

Language: Английский

Citations

126
Cushing's syndrome DOI
Mônica R. Gadelha, Federico Gatto, Luiz Eduardo Wildemberg

et al.

The Lancet, Journal Year: 2023, Volume and Issue: 402(10418), P. 2237 - 2252

Published: Nov. 17, 2023

Language: Английский

Citations

52
Pituitary neuroendocrine tumors with PIT1/SF1 co-expression show distinct clinicopathological and molecular features DOI Creative Commons
Matthias Dottermusch, Alice Ryba, Franz Ricklefs

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: Jan. 16, 2024

Abstract Pituitary neuroendocrine tumors (PitNETs) are classified according to cell lineage, which requires immunohistochemistry for adenohypophyseal hormones and the transcription factors (TFs) PIT1, SF1, TPIT. According current WHO 2022 classification, PitNETs with co-expression of multiple TFs termed “plurihormonal”. Previously, PIT1/SF1 was prevailingly reported in PitNETs, otherwise correspond somatotroph lineage. However, little is known about such classification has not recognized their significance. We compiled an in-house case series 100 tumors, previously diagnosed as PitNETs. Following TF staining, histopathological features associated were assessed. Integration publicly available sample data allowed a meta-analysis SF1-associated clinicopathological molecular across total 270 The majority (74%, 52/70) our densely granulated (DGST) unequivocally co-expressed PIT1 SF1 (DGST-PIT1/SF1). None (0%, 0/30) sparsely (SGST) stained positive (SGST-PIT1). Among DGST, significantly scarce FSH/LH expression fewer fibrous bodies compared DGST-PIT1. Integrated analyses including samples confirmed that DGST-PIT1/SF1, DGST-PIT1 SGST-PIT1 represent distinct tumor subtypes. Clinicopathological meta-analyses indicated respond more favorably towards treatment somatostatin analogs while both these subtypes show overall less aggressive clinical course than SGST-PIT1. In this study, we spotlight DGST common, yet underrecognized, PitNET subtype. Our study questions rationale generally classifying “plurihormonal”, calls refinement classification. propose term “somatogonadotroph PitNET”.

Language: Английский

Citations

18
Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms DOI Creative Commons

Vinaya Srirangam Nadhamuni,

Márta Korbonits

Endocrine Reviews, Journal Year: 2020, Volume and Issue: 41(6), P. 821 - 846

Published: March 23, 2020

Abstract Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over last few years we recognized role germline and somatic mutations a number syndromic or nonsyndromic conditions with tumor predisposition. These include identification novel variants patients familial simplex tumors establishment identified through next generation sequencing. Advanced techniques allowed exploration epigenetic mechanisms mediated DNA methylation, histone modifications noncoding RNAs, such as microRNA, long RNAs circular RNAs. can influence formation, growth, invasion. While genetic often disrupt similar pathways, cell cycle regulation, there is little overlap between genes altered by germline, somatic, mechanisms. The interplay these complex driving tumorigenesis are best studied emerging multiomics studies. Here, summarize insights from recent developments regulation tumorigenesis.

Language: Английский

Citations

86
Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms DOI Creative Commons
Zidong Zhang, Michel Zamojski, Gregory R. Smith

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(10), P. 110467 - 110467

Published: March 1, 2022

Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a single nucleus RNA-seq ATAC-seq resource from pediatric, adult, aged postmortem pituitaries (snpituitaryatlas.princeton.edu) characterize cell-type-specific gene expression chromatin accessibility programs for all major cell lineages. identify uncommitted PSCs, committing progenitor cells, sex differences. Pseudotime trajectory analysis indicates that early-life PSCs distinct the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain sites transcription factors significantly associated with compared types within PSCs. deterministic mechanisms contribute to heterogeneous marker These findings lineages reveal diverse regulating key PSC genes type identity.

Language: Английский

Citations

48
Integrated proteogenomic characterization across major histological types of pituitary neuroendocrine tumors DOI Creative Commons
Fan Zhang, Qilin Zhang, Jiajun Zhu

et al.

Cell Research, Journal Year: 2022, Volume and Issue: 32(12), P. 1047 - 1067

Published: Oct. 28, 2022

Abstract Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive heterogeneity and lack high-quality tissues for biomarker discovery, causative molecular mechanisms are far from being fully defined. Therefore, more studies needed improve current clinicopathological classification system, advanced treatment strategies such as targeted therapy immunotherapy yet be explored. Here, we performed largest integrative genomics, transcriptomics, proteomics, phosphoproteomics analysis reported date a cohort 200 PitNET patients. Genomics data indicate that GNAS copy number gain can serve reliable diagnostic marker hyperproliferation PIT1 lineage. Proteomics-based PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into invasive subgroup. Further potential therapeutic targets, including CDK6, TWIST1, EGFR, VEGFR2, different clusters. Immune subtyping explore application in an association between alterations JAK1-STAT1-PDL1 axis immune exhaustion, changes JAK3-STAT6-FOS/JUN infiltration. These alternations various clusters/subtypes were further confirmed independent 750 This proteogenomic across traditional histological boundaries improves our understanding pathophysiology suggests novel targets strategies.

Language: Английский

Citations

42
Aggressive Pituitary Tumors and Pituitary Carcinomas: From Pathology to Treatment DOI Creative Commons
Pia Burman, Olivera Casar‐Borota, Luis Gustavo Perez‐Rivas

et al.

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2023, Volume and Issue: 108(7), P. 1585 - 1601

Published: Feb. 28, 2023

Abstract Aggressive pituitary tumors (APTs) and carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, course, response therapy. Half of them show an aggressive course only many years after the first apparently benign presentation. APTs PCs share several properties, but a Ki67 index greater than or equal 10% extensive p53 expression more prevalent in PCs. Mutations TP53 ATRX most common genetic alterations; their detection might be value for early identification aggressiveness. Treatment requires multimodal approach including surgery, radiotherapy, drugs. Temozolomide is recommended first-line chemotherapy, rates about 40%. Immune checkpoint inhibitors have emerged as second-line treatment PCs, currently no evidence superior effect dual therapy compared monotherapy PD-1 blockers. Bevacizumab has resulted partial (PR) few patients; tyrosine kinase everolimus generally not been useful. The peptide receptor radionuclide limited well. Management APT/PC challenging should discussed within expert team consideration pathological findings, age, general condition patient. Considering that APT/PCs rare, new therapies preferably evaluated shared standardized protocols. Prognostic predictive markers guide decisions needed scope ongoing research.

Language: Английский

Citations

39