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Journal of the American Veterinary... Aug 2019
Topics: Adrenal Gland Neoplasms; Animals; Cat Diseases; Cats; Female; Pheochromocytoma
PubMed: 31355720
DOI: 10.2460/javma.255.4.433 -
Frontiers in Endocrinology 2022Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage. This has resulted in an increasing use of the term "silent" PPGL. This term and other variants are now commonly found in the literature without any clear or unified definition. Among the various terms, "clinically silent" is often used to describe the lack of signs and symptoms associated with catecholamine excess. Confusion arises when these and other terms are used to define the tumors according to their ability to synthesize and/or release catecholamines in relation to biochemical test results. In such cases the term "silent" and other variants are often inappropriately and misleadingly used. In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Catecholamines
PubMed: 36325453
DOI: 10.3389/fendo.2022.1021420 -
Frontiers in Endocrinology 2022The aim of the study was to assess the total antioxidant/oxidant status in the plasma and urine of patients with adrenal tumors. The study group consisted of 60 patients...
The aim of the study was to assess the total antioxidant/oxidant status in the plasma and urine of patients with adrenal tumors. The study group consisted of 60 patients (31 women and 29 men) with adrenal masses, classified into three subgroups: non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma. The number of patients was set based on our previous experiment (α = 0.05, test power = 0.9). Antioxidant activity (Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Oxidative Stress Index (OSI)) and antiradical activity (Radical-Scavenging Activity Assay (DPPH), Ferric-Reducing Antioxidant Power (FRAP)) were measured using colorimetric methods. FRAP level was decreased in plasma and urine incidentaloma , pheochromocytoma and Cushing's/Conn's adenoma , while DPPH antiradical activity only in plasma of patients with adrenal masses . Plasma TAC was increased in incidentaloma patients , whereas in pheochromocytoma group ) was decreased. Plasma and urine TOS and OSI were significantly higher in patients with adrenal tumors. In pheochromocytoma patients, plasma and urine TAC , as well as plasma plasma DPPH and urine FRAP correlated positively with normethanephrine. We are the first who showed reduced radical scavenging capacity in the plasma/urine of patients with adrenal masses. Nevertheless, plasma TAC was significantly higher in the incidentaloma group compared to controls. Therefore, plasma and urinary antioxidant and antiradical activities depend on the presence of the tumor. Lower levels of TAC, DPPH and FRAP clearly indicate a reduced ability to scavenge free radicals and thus a lack of effective protection against oxidative stress in patients with adrenal tumors. Both plasma and urine redox biomarkers can be used to assess systemic antioxidant status in adrenal tumor patients.
Topics: Adenoma; Adrenal Gland Neoplasms; Antioxidants; Biomarkers; Female; Humans; Male; Oxidants; Pheochromocytoma
PubMed: 36246875
DOI: 10.3389/fendo.2022.1011043 -
LaeknabladidWe report a case of a man with a 30-year history of treatment-resistant hypertension, hydropoiesis, tachycardic spells and dysgeusia. Despite repeated visits to the...
We report a case of a man with a 30-year history of treatment-resistant hypertension, hydropoiesis, tachycardic spells and dysgeusia. Despite repeated visits to the emergency department and work-up in an out-patient clinic, the diagnosis was unknown. Three years prior to remittance to an endocrinologist, the hypertension worsened, and he developed diabetes type-II. Further work-up revealed a 3 cm extra-adrenal pheochromocytoma, a paraganglioma. After surgical removal of the tumor, he is without medication and symptom free. Pheochromocytoma and paraganglioma are rare causes of hypertension, estimated to explain 0.1-0.6% of all cases, but nonetheless an important diagnosis to make, due to serious side effects.
Topics: Male; Humans; Pheochromocytoma; Paraganglioma; Ambulatory Care Facilities; Hypertension; Adrenal Gland Neoplasms
PubMed: 36856470
DOI: 10.17992/lbl.2023.03.735 -
Oncology Research 2022Epigenetic mechanisms, such as DNA methylation and histone modifications (e.g., acetylation and deacetylation), are strongly implicated in the carcinogenesis of various... (Review)
Review
Epigenetic mechanisms, such as DNA methylation and histone modifications (e.g., acetylation and deacetylation), are strongly implicated in the carcinogenesis of various malignancies. During transcription, the expression and functionality of coding gene products are altered following the histone acetylation and deacetylation. These processes are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. HDAC inhibitors (HDACis) have been developed as promising therapeutic agents, to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some specific malignant diseases with limited options. Mechanistically, these agents affect many intracellular pathways, including cell cycle arrest, apoptosis and differentiation, and their mechanism of action mainly depends on the type of cancer. Currently, five HDACis have been approved for the treatment of several hematological malignancies (e.g., T-cell lymphoma subtypes and multiple myeloma); while, many of them are tested for further therapeutic indications in solid tumors (e.g., colorectal, thyroid, breast, lung and pancreatic cancer). Herein, we review the literature and gather all available evidence, from and data to clinical trial results, that recognizes the antitumor activity of HDACis on pheochromocytomas and paragangliomas; and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.
Topics: Humans; Pheochromocytoma; Histone Deacetylase Inhibitors; Paraganglioma; Pancreatic Neoplasms; Adrenal Gland Neoplasms
PubMed: 37305348
DOI: 10.32604/or.2022.026913 -
Anatolian Journal of Cardiology Aug 2022
Topics: Adrenal Gland Neoplasms; Humans; Pheochromocytoma; Takotsubo Cardiomyopathy
PubMed: 35924295
DOI: 10.5152/AnatolJCardiol.2022.2038 -
Journal of Cachexia, Sarcopenia and... Dec 2022Maintaining intraoperative haemodynamic stability can reduce cardiovascular complications during surgery for pheochromocytoma and paraganglioma (PPGL). Risk factors such...
BACKGROUND
Maintaining intraoperative haemodynamic stability can reduce cardiovascular complications during surgery for pheochromocytoma and paraganglioma (PPGL). Risk factors such as tumour size and catecholamine levels are reported to predict haemodynamic responses during surgery for PPGL. We hypothesized that additional factors including body composition and genetic information could further improve prediction.
METHODS
Consecutive patients with PPGL confirmed by surgical pathology between June 2010 and June 2019 were retrospectively included. Cross-sectional computed tomography images at the L3 level were used to assess body composition parameters including skeletal muscle area and visceral fat area. Next-generation sequencing was performed using a panel containing susceptibility genes of PPGL. Differences in clinical-genetic characteristics and body composition parameters were analysed and compared in patients with and without intraoperative haemodynamic instability (HDI).
RESULTS
We included 221 patients with PPGL (median age 47 [38-56] years, and 52% male). Among them, 49.8% had Cluster 2 mutations (related to kinase signalling pathways), 44.8% had sarcopenia, and 52.9% experienced intraoperative HDI. Compared with patients without HDI, more patients with HDI had Cluster 2 mutations (59.8% vs. 38.5%, P = 0.002) and less had sarcopenia (35.9% vs. 54.8%, P = 0.005). Multivariate analysis showed that urine vanillylmandelic acid ≥ 58 μmol/day (adjusted odds ratio [OR] = 1.840, 95% confidence interval [CI] = 1.012-3.347, P = 0.046), tumour size ≥ 4 cm (adjusted OR = 2.278, 95% CI = 1.242-4.180, P = 0.008), and Cluster 2 mutations (adjusted OR = 2.199, 95% CI = 1.128-4.285, P = 0.021) were independent risk factors for intraoperative HDI, while sarcopenia (adjusted OR = 0.475, 95% CI = 0.266-0.846, P = 0.012) decreased the risk.
CONCLUSIONS
Body composition and genotype were associated with intraoperative haemodynamics in patients with PPGL. Our results indicated that inclusion of body composition and genotype in the overall assessment of patients with PPGL helped to predict HDI during surgery, which could assist in implementing preoperative and intraoperative measures to reduce perioperative complications.
Topics: Humans; Male; Middle Aged; Female; Retrospective Studies; Cross-Sectional Studies; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Body Composition
PubMed: 36068986
DOI: 10.1002/jcsm.13071 -
Medecine Sciences : M/S Mar 2022Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes...
Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes encoding SDH are responsible for a predisposition to pheochromocytomas and paragangliomas, and more rarely, to gastrointestinal stromal tumors or renal cell carcinomas. A decrease in SDH activity, not explained by genetics, has also been observed in more common cancers. One of the consequences of the inactivation of SDH is the excessive production of its substrate, succinate, which acts as an oncometabolite by promoting a pseudohypoxic status and an extensive epigenetic rearrangement. Understanding SDH-related oncogenesis now makes it possible to develop innovative diagnostic methods and to consider targeted therapies for the management of affected patients.
Topics: Adrenal Gland Neoplasms; Gastrointestinal Stromal Tumors; Humans; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 35333162
DOI: 10.1051/medsci/2022024 -
Journal of Clinical Ultrasound : JCU Jan 2023To analyze the correlation between catecholamines and echocardiographic parameters in patients with pheochromocytoma and paraganglioma (PPGL).
PURPOSE
To analyze the correlation between catecholamines and echocardiographic parameters in patients with pheochromocytoma and paraganglioma (PPGL).
METHODS
Sixty-six patients who underwent surgical resection of pathologically proven PPGL from January 2016 to June 2019 were examined. Echocardiographic parameters were compared between patients with elevated catecholamine concentrations and those with normal concentrations.
RESULTS
The percentage of patients with elevation of any catecholamine (NE, DA, or E, and their metabolites) did not significantly differ between patients with normal and abnormal left ventricular ejection function (LVEF) or diastolic function (LVDF). E wave deceleration time (EDT) was significantly lower in patients with elevation of any catecholamine than in those with normal concentrations (p = 0.024). EDT was significantly lower in patients with elevated NE and its metabolites than in patients with normal NE concentration (p = 0.004). After adjusting for gender and age, EDT was significantly negatively correlated with elevated NE and its metabolites in regression analysis (B-value, -39.853; p = 0.023) and correlation analysis (r = -0.349; p = 0.004).
CONCLUSION
NE and its metabolites may have an impact on left ventricular diastolic function, which can be reflected by EDT. EDT was negatively correlated with elevated NE and its metabolites.
Topics: Humans; Pheochromocytoma; Catecholamines; Paraganglioma; Echocardiography; Adrenal Gland Neoplasms; Ventricular Dysfunction, Left
PubMed: 36054716
DOI: 10.1002/jcu.23290 -
PLoS Genetics Jun 2020Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important...
Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; HEK293 Cells; Humans; Male; Mutation, Missense; Myosin Heavy Chains; Myosin Type V; Neoplasm Metastasis; Pheochromocytoma
PubMed: 32511227
DOI: 10.1371/journal.pgen.1008803