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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 -
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 -
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 -
Frontiers in Endocrinology 2023Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and... (Review)
Review
Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and pathophysiological similarities. In addition to the typical triad of paroxysmal headache, palpitation, and sweating, PPGL may also be accompanied by symptoms and signs involving multiple organs and systems such as the cardiovascular system, digestive system, endocrine system, and nervous system. Currently, surgical resection is the first choice for PPGL. Safe and effective surgical management of complicated PPGL is the goal of clinical work. In this paper, we discuss this hot issue based on complicated PPGL cases, aiming to share our experience of the surgical management strategy of PPGL.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Neuroendocrine Tumors; Catecholamines
PubMed: 37152961
DOI: 10.3389/fendo.2023.1129622 -
Frontiers in Endocrinology 2023Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells, holding significant clinical importance due to their... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells, holding significant clinical importance due to their capacity for excessive catecholamine secretion and associated cardiovascular complications. Roughly 80% of cases are associated with genetic mutations. Based on the functionality of these mutated genes, PPGLs can be categorized into distinct molecular clusters: the pseudohypoxia signaling cluster (Cluster-1), the kinase signaling cluster (Cluster-2), and the WNT signaling cluster (Cluster-3). A pivotal factor in the pathogenesis of PPGLs is hypoxia-inducible factor-2α (HIF2α), which becomes upregulated even under normoxic conditions, activating downstream transcriptional processes associated with pseudohypoxia. This adaptation provides tumor cells with a growth advantage and enhances their ability to thrive in adverse microenvironments. Moreover, pseudohypoxia disrupts immune cell communication, leading to the development of an immunosuppressive tumor microenvironment. Within Cluster-1a, metabolic perturbations are particularly pronounced. Mutations in enzymes associated with the tricarboxylic acid (TCA) cycle, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH), isocitrate dehydrogenase (IDH), and malate dehydrogenase type 2 (MDH2), result in the accumulation of critical oncogenic metabolic intermediates. Notable among these intermediates are succinate, fumarate, and 2-hydroxyglutarate (2-HG), which promote activation of the HIFs signaling pathway through various mechanisms, thus inducing pseudohypoxia and facilitating tumorigenesis. SDHx mutations are prevalent in PPGLs, disrupting mitochondrial function and causing succinate accumulation, which competitively inhibits α-ketoglutarate-dependent dioxygenases. Consequently, this leads to global hypermethylation, epigenetic changes, and activation of HIFs. In FH-deficient cells, fumarate accumulation leads to protein succination, impacting cell function. FH mutations also trigger metabolic reprogramming towards glycolysis and lactate synthesis. IDH1/2 mutations generate D-2HG, inhibiting α-ketoglutarate-dependent dioxygenases and stabilizing HIFs. Similarly, MDH2 mutations are associated with HIF stability and pseudohypoxic response. Understanding the intricate relationship between metabolic enzyme mutations in the TCA cycle and pseudohypoxic signaling is crucial for unraveling the pathogenesis of PPGLs and developing targeted therapies. This knowledge enhances our comprehension of the pivotal role of cellular metabolism in PPGLs and holds implications for potential therapeutic advancements.
Topics: Humans; Pheochromocytoma; Citric Acid Cycle; Ketoglutaric Acids; Paraganglioma; Adrenal Gland Neoplasms; Mutation; Succinates; Succinic Acid; Signal Transduction; Fumarates; Dioxygenases; Tumor Microenvironment
PubMed: 37867526
DOI: 10.3389/fendo.2023.1274239 -
BMC Cardiovascular Disorders Jun 2024Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of...
BACKGROUND
Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of these tumors have been described, there have been no large-scale investigations of the profile of HT and changes in cardiac structure and function that occur in patients with pheochromocytomas and paragangliomas (PPGL).
MATERIALS AND METHODS
In this study, we investigated the prevalence of HT and left ventricular remodeling (LVR) in a cohort of 598 patients who underwent surgery for PPGL at our center between January 2001 and April 2022. Information on demographics, reason for hospitalization, medical history, biochemical parameters, findings on echocardiography, and tumor characteristics were recorded. The LVR index was compared according to whether or not there was a history of HT.
RESULTS
The average age was 47.07 ± 15.07 years, and 277 (46.32%) of the patients were male. A history of HT was found in 423 (70.74%) of the 598 patients. Paraganglioma was significantly more common in the group with HT (26.00% vs. 17.71%, P = 0.030) and significantly less likely to be found incidentally during a health check-up in this group (22.93% vs. 59.43%, P < 0.001). Among 365 patients with complete echocardiography data, left ventricular mass index (86.58 ± 26.70 vs. 75.80 ± 17.26, P < 0.001) and relative wall thickness (0.43 ± 0. 08 vs. 0.41 ± 0.06, P = 0.012) were significantly higher in patients with PPGL and a history of HT. The proportions with left ventricular hypertrophy (LVH) (19.40% vs. 8.25%, P = 0.011) and LVR (53.73% vs. 39.18%, P = 0.014) were also higher when there was a history of HT. After adjusting for age, gender, body mass index, alcohol consumption, smoking status, diabetes, stroke, creatinine level, tumor location, and tumor size, a history of HT was significantly correlated with LVH (odds ratio 2.71, 95% confidence interval 1.18-6.19; P = 0.018) and LVR (odds ratio 1.83, 95% confidence interval 1.11-3.03; P = 0.018).
CONCLUSION
HT is common in patients with PPGL (70.74% in this cohort). PPGL without a history of HT is more likely to be found incidentally (59.43% in our cohort). HT is associated with LVR in PPGL patients with complete echocardiography data. These patients should be observed carefully for cardiac damage, especially those with a history of HT.
Topics: Humans; Pheochromocytoma; Male; Female; Middle Aged; Adrenal Gland Neoplasms; Adult; Ventricular Remodeling; Paraganglioma; Hypertension; Prevalence; Retrospective Studies; Ventricular Function, Left; Risk Factors; Risk Assessment; Aged; Blood Pressure
PubMed: 38926862
DOI: 10.1186/s12872-024-03936-6 -
Journal of Bronchology & Interventional... Jul 2020
Topics: Biopsy; Bronchial Neoplasms; Bronchoscopy; Humans; Immunohistochemistry; Lasers, Solid-State; Male; Middle Aged; Paraganglioma; Respiratory Distress Syndrome; Spirometry; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32205710
DOI: 10.1097/LBR.0000000000000667 -
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 -
Internal Medicine (Tokyo, Japan) Nov 2021
Topics: Adrenal Gland Neoplasms; Humans; Paraganglioma; Pheochromocytoma
PubMed: 34024860
DOI: 10.2169/internalmedicine.7413-21 -
Polski Przeglad Chirurgiczny Nov 2020Carotid Body Tumor i.e. Paraganglioma is a challenging entity from the point of multidisciplinary diagnosis. The main treatment option i.e. surgery yields intraoperative... (Review)
Review
Carotid Body Tumor i.e. Paraganglioma is a challenging entity from the point of multidisciplinary diagnosis. The main treatment option i.e. surgery yields intraoperative risk,related to cranial nerve palsy and vascular morbidity.Bifurcation of Common Carotid Artery especially at the Carotid Body is the place where Head and Neck Paraganglioma is most frequently seen i.e. 60% of incidence [19]. Indeed, the knowledge of genetic germline SDH mutations, which cause deregulation of hypoxia-induced factors yields better understanding of the tumor nature. It is recommended to conduct selective neck dissection in regions IIA, IIB, III to exlude malignant transformation and metastasis, due to malignant potential of Carotid Body Tumors, especially in case of SDHB mutation. SDHD mutation is the main cause of hereditary HNPGLs. Computed tomography (CT), magnetic resonance imaging (MRI) and angiography yield thorough assessment of paraganglioma extension. In large size tumors, embolization of supplying artery under guidance of angiography may be considered. In case of Carotid Body Tumor, differential diagnosis should include: carotid artery aneurysm, lymphadenopathy, Schwannoma of the hypoglossal nerve or acessory thyroid gland.
Topics: Carotid Body Tumor; Female; Head and Neck Neoplasms; Humans; Male; Neoplasm Staging; Paraganglioma
PubMed: 33408267
DOI: 10.5604/01.3001.0014.4872