Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant.
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ABSTRACT:
SUBMITTER: Ku CR
PROVIDER: S-EPMC8368009 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Data from 12 fresh-frozen somatotropinomas and their corresponding blood samples. Details are given in Valimaki et al. Whole-genome sequencing of Growth Hormone (GH) -secreting Pituitary Adenoma. Provisionally accepted, 2015.
| EGAS00001001293 | EGA
Project description:We profiled the somatic landscape of 21 growth hormone (GH) -secreting pituitary adenomas using somatic copy-number alteration (SCNA), whole-genome sequencing (WGS), bisulfate sequencing, and transcriptome approaches. See details in Valimaki et al. Genetic and epigenetic characterization of growth hormone (GH) - secreting pituitary tumors. Manuscript in preparation, 2019.
| EGAS00001003488 | EGA
Project description:PurposeGrowth 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.MethodsSix 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.ResultsTotally, 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.ConclusionsOur 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.
| S-EPMC9584994 | biostudies-literature
Project description:PurposeTo assess the quantitative gray matter volume of the limbic system in growth hormone-secreting pituitary adenoma (GHPAs) patients and its correlation to cognitive function.Method91 right-handed patients with pituitary adenomas were retrospectively included from the First Affiliated Hospital of Sun Yat-sen University -48 with GHPAs and 43 with non-functioning pituitary adenomas (NFPAs). Participants underwent serum hormone assessment, regular sellar MRI scanning with T1WI-MPRAGE. Cognitive function was gauged using MoCA and MMSE. Brain region auto-segmentation and gray matter volume calculation were conducted on the Brainsite platform.ResultsCompared to NFPAs patients, GHPAs patients had higher gray matter volume (758,285 vs 674,610 mm³, p < 0.001). No significant volumetric differences in both sides of limbic system gray matter while there were evident differences in the relative volumes of limbic system gray matter between groups. GHPAs patients scored lower on MOCA (24.0 (2.18) vs 25.1 (2.28), p < 0.031), with no difference in MMSE. We observed a significant correlation between the relative limbic volume and MOCA scales, while no evident correlation was found between relative limbic volume and serum hormone or tumor aggressiveness. Univariate and multivariate Logistic regression showed that hippocampus and limbic cortex (parahippocampal gyrus and internal olfactory area) of advantageous hemisphere correlated significantly with occurrence of mild cognitive impairment with the C-statistic reaching 0.90.ConclusionPatients with GHPAs show a relative decrease in limbic gray matter volume, especially in the hippocampus and limbic cortex of the dominant hemisphere, which is associated with mild cognitive impairment.
| S-EPMC11365443 | biostudies-literature
Project description:BackgroundThe growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1.Methods29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging.ResultsCompared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR < 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR < 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR < 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE < 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE < 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly.ConclusionsOur findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.
| S-EPMC8072046 | biostudies-literature
Project description:A 40-year-old woman presented with galactorrhea and oligomenorrhea. She had a history of multiple ovarian cysts and pelvic pain.Laboratory evaluation included measurements of the levels of estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone, free endogenous T4, the glycoprotein hormone alpha subunit, cortisol, adrenocorticotropic hormone, and insulin-like growth factor I. Radiological studies included MRI of the pituitary.Ovarian hyperstimulation syndrome caused by a pituitary adenoma, secreting follicle-stimulating hormone.The patient underwent trans-sphenoidal resection of the adenoma, with subsequent normalization of hormonal values and symptoms.
| S-EPMC2777809 | biostudies-literature
Project description:Prior study has demonstrated that gut microbiota at the genus level is significantly altered in patients with growth hormone (GH)-secreting pituitary adenoma (GHPA). Yet, no studies exist describing the state of gut microbiota at species level in GHPA. We performed a study using 16S rRNA amplicon sequencing in a cohort of patients with GH-secreting pituitary adenoma (GHPA, n = 28) and healthy controls (n = 67). Among them, 9 patients and 10 healthy controls were randomly chosen and enrolled in metagenomics shotgun sequencing, generating 280,426,512 reads after aligning to NCBI GenBank DataBase to acquire taxa information at the species level. Weighted UniFrac analysis revealed that microbial diversity was notably decreased in patients with GHPA, consistent with a previous study. With 16S rRNA sequencing, after correction for false-discovery rate (FDR), rank-sum test at the genus level revealed that the relative abundance of Oscillibacter and Enterobacter was remarkably increased in patients and Blautia and Romboutsia genera predominated in the controls, augmented by additional LEfSe (linear discriminant analysis effect size) analysis. As for further comparison at the species level with metagenomics sequencing, rank-sum test together with LEfSe analysis confirmed the enrichment of Alistipes shahii and Odoribacter splanchnicus in the patient group. Notably, LEfSe analysis with metagenomics also demonstrated that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND, derived from Enterobacter, were both significantly enriched in patients. Functional analysis showed that amino acid metabolism pathway was remarkably enriched in GHPA, while carbohydrate metabolism pathway was notably enriched in controls. Further, significant positive correlations were observed between Enterobacter and baseline insulin-like growth factor 1 (IGF-1), indicating that Enterobacter may be strongly associated with GH/IGF-1 axis in GHPA. Our data extend our insight into the GHPA microbiome, which may shed further light on GHPA pathogenesis and facilitate the exploration of novel therapeutic targets based on microbiota manipulation. IMPORTANCE Dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extraintestinal diseases. Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of GH and IGF-1, causing increased morbidity and mortality. Researches have reported that the GH/IGF-1 axis exerts its own influence on the intestinal microflora. Here, the results showed that compared with healthy controls, GHPA patients not only decreased the alpha diversity of the intestinal flora but also significantly changed their beta diversity. Further, metagenomics shotgun sequencing in the present study exhibited that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND were enriched in patients. Also, we were pleasantly surprised to find that the Enterobacter genus was strongly positively correlated with baseline IGF-1 levels. Collectively, our work provides the first glimpse of the dysbiosis of the gut microbiota at species level, providing a better understanding of the pathophysiological process of GHPA.
| S-EPMC8754134 | biostudies-literature
Project description:BackgroundBone loss and high risk of fractures have been reported in patients with primary hyperthyroidism, whereas data on skeletal health in TSH-secreting adenoma (TSH-oma) are scant, and the risk of fractures in this specific clinical context has not been investigated so far. In this cross-sectional study, we aimed at evaluating for the first time, to our knowledge, the prevalence and determinants of radiological vertebral fractures (VFs) in patients with TSH-oma.MethodsTwenty-two patients (10 males, 12 females; median age 47 years) with TSH-oma and 44 patients (20 males, 24 females; median age 49 years) with nonfunctioning pituitary adenoma (NFPA) were retrospectively evaluated for thoracic VFs using a morphometric approach on lateral chest X-ray routinely performed in the presurgical diagnostic workup.ResultsThe prevalence of VFs was significantly higher in TSH-oma vs NFPA (59.1% vs 22.7%; P = 0.003), the difference being still significant (odds ratio, 10.5; P = 0.005) after correction for the size of pituitary adenomas and biochemical parameters. In TSH-oma, the prevalence of VFs was significantly associated with older age (P = 0.007) and higher serum free T4 values (P = 0.02). In 20 patients, data on presurgical medical therapies of TSH-oma were available. All patients not treated with somatostatin receptor ligands were fractured compared with 25% of those who were treated with these drugs (P = 0.001). No significant (P = 0.25) association between VFs and treatment with methimazole was found.ConclusionsThis study provides the first evidence, to our knowledge, that patients with TSH-oma may develop VFs in close relationship with severity of hyperthyroidism.
| S-EPMC6125713 | biostudies-literature
Project description: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. Supplementary Information The online version contains supplementary material available at 10.1186/s12902-023-01334-1.
| S-EPMC10131333 | biostudies-literature
Project description:An effective treatment for the management of adrenocorticotropic hormone-secreting pituitary adenomas (ACTH-PA) is currently lacking, although surgery is a treatment option. We have integrated information obtained at the metabolomic and proteomic levels to identify critical networks and signaling pathways that may play important roles in the metabolic regulation of ACTH-PA and therefore hopefully represent potential therapeutic targets. Six ACTH-PAs and seven normal pituitary glands were investigated via gas chromatography-mass spectrometry (GC-MS) analysis for metabolomics. Five ACTH-PAs and five normal pituitary glands were subjected to proteomics analysis via nano liquid chromatography tandem-mass spectrometry (nanoLC-MS/MS). The joint pathway analysis and network analysis was performed using MetaboAnalyst 3.0. software. There were significant differences of metabolites and protein expression levels between the ACTH-PAs and normal pituitary glands. A proteomic analysis identified 417 differentially expressed proteins that were significantly enriched in the Myc signaling pathway. The protein-metabolite joint pathway analysis showed that differentially expressed proteins and metabolites were significantly enriched in glycolysis/gluconeogenesis, pyruvate metabolism, citrate cycle (TCA cycle), and the fatty acid metabolism pathway in ACTH-PA. The protein-metabolite molecular interaction network identified from the metabolomics and proteomics investigation resulted in four subnetworks. Ten nodes in subnetwork 1 were the most significantly enriched in cell amino acid metabolism and pyrimidine nucleotide metabolism. Additionally, the metabolite-gene-disease interaction network established nine subnetworks. Ninety-two nodes in subnetwork 1 were the most significantly enriched in carboxylic acid metabolism and organic acid metabolism. The present study clarified the pathway networks that function in ACTH-PA. Our results demonstrated the presence of downregulated glycolysis and fatty acid synthesis in this tumor type. We also revealed that the Myc signaling pathway significantly participated in the metabolic changes and tumorigenesis of ACTH-PA. This data may provide biomarkers for ACTH-PA diagnosis and monitoring, and could also lead to the development of novel strategies for treating pituitary adenomas.
| S-EPMC6266547 | biostudies-literature