Metabolic Alterations in Patients with Pheochromocytoma

Erlic, Zoran; Beuschlein, Felix

doi:10.1055/a-0649-0960

Cited by 24 publications

(33 citation statements)

References 69 publications

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“…Pheochromocytoma can be classified as a metabolic disease due to the increased secretion of catecholamines such as dopamine, adrenaline, and noradrenaline. Indeed, catecholamines are involved in the regulation of many metabolic pathways, and therefore, patients with phaeochromocytoma may have impaired glucose metabolism, insulin resistance, and lipid metabolism disorders [ 65 , 66 ]. Pheochromocytoma is also a secondary cause of diabetes mellitus, which, in some patients, may be the only clinical symptom of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients

Choromańska

Myśliwiec

Kozłowski

et al. 2021

Oxidative Medicine and Cellular Longevity

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This study is the first to assess redox balance, glutathione metabolism, and oxidative damage to RNA/DNA, proteins, and lipids in the plasma/serum and urine of patients with adrenal masses. The study included 70 patients with adrenal tumors divided into three subgroups: incidentaloma ( n = 30 ), pheochromocytoma ( n = 20 ), and Cushing’s/Conn’s adenoma ( n = 20 ), as well as 60 healthy controls. Blood and urine samples were collected before elective endoscopic adrenalectomy. Antioxidant defense capacity was significantly decreased (serum/plasma: superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), uric acid (UA); urine: SOD, GSH, UA) in patients with adrenal masses. The oxidative damage to proteins (advanced glycation end products (AGE), advanced oxidation protein products (AOPP)) and lipids (lipid hydroperoxides (LOOH), and malondialdehyde (MDA)) was higher in the plasma and urine of these patients. Plasma MDA and DNA/RNA oxidation products, with high sensitivity and specificity, can help to diagnose pheochromocytoma. This biomarker differentiates patients with pheochromocytoma from Cushing’s/Conn’s adenoma as well as from heathy controls. Plasma RNA/DNA oxidation was also positively correlated with urine metanephrine. Oxidative stress can play a crucial role in adrenal tumors. However, further studies are required to clarify the role of redox signaling in adrenal masses.

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Section: Discussionmentioning

confidence: 99%

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients

Choromańska

Myśliwiec

Kozłowski

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Similar findings were observed after treatment of pheochromocytoma in another study by Bosanska et al [17], albeit a significant reduction in HDL-C was not observed. Moreover, it is possible that an elevated HDL-C in patients with pheochromocytoma could be considered an indirect effect of catecholamines-induced thermogenic activation of adipocytes [18,19].…”

Section: Discussionmentioning

confidence: 99%

Impaired Glucose Metabolism in People with Extremely Elevated High-Density Lipoprotein Cholesterol and Low Alcohol Consumption: Results of the Kanagawa Investigation of Total Checkup Data from the National Database-3 (KITCHEN-3)

Nakajima

Higuchi

2019

JCM

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Background: Recently, we have shown that extremely high high-density lipoprotein cholesterol (HDL-C), which was observed mostly in heavy drinkers, was associated with the incidence of diabetes. However, the observed association was influenced by the consumption of alcohol. Furthermore, it is unknown whether impaired glucose metabolism exists in people with extremely high HDL-C, regardless of their alcohol consumption. Therefore, we addressed this issue in people who did not have a habit of drinking alcohol. Methods: In this community-based cross-sectional study, we included 177,034 participants (40–74 years old) who reported being nondrinkers. We investigated levels of HbA1c, fasting plasma glucose (FPG), HDL-C, and clinical parameters according to 11 levels of HDL-C concentration from 20 to 120 mg/dL or over. Results: A total of 6112 participants with HDL-C ≥ 100 mg/dL (3.5%) showed a better lipid profile, higher prevalence amongst women, more habitual exercise, a lower prevalence of smoking, and lower body mass index (BMI). Compared with an HDL-C of 70–79 mg/dL, HDL-C ≤ 69 mg/dL (except an HDL-C of 20–29 mg/dL) and HDL-C ≥ 90 mg/dL were significantly associated with a high HbA1c of ≥6.0%, independently of confounding factors. This finding was distinctly demonstrated in women. Similar trends were observed when high HbA1c was replaced with high FPG (≥110 mg/dL). Conclusions: Our study demonstrated that impaired glucose metabolism may exist in people with extremely high HDL-C and who hardly drink alcohol.

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“…Catecholamines play a crucial role in the regulation of multiple metabolic pathways. Patients with PPGLs usually manifest with impaired insulin secretion, increased insulin resistance, elevated lipolysis, and the bone resorption marker C-terminal telopeptide of type I collagen (110). Many studies have revealed that oncometabolite such as succinate, fumarate, and 2-hydroxyglutarate (2HG) are increased in PPGLs (83,111,112).…”

Section: The Mechanisms In Dysregulated Vhl/hif Axis and Ppglsmentioning

confidence: 99%

The VHL/HIF Axis in the Development and Treatment of Pheochromocytoma/Paraganglioma

et al. 2020

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Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic or parasympathetic paraganglia (PGLs). About 40% of PPGLs result from germline mutations and therefore they are highly inheritable. Although dysfunction of any one of a panel of more than 20 genes can lead to PPGLs, mutations in genes involved in the VHL/HIF axis including PHD, VHL, HIF-2A (EPAS1), and SDHx are more frequently found in PPGLs. Multiple lines of evidence indicate that pseudohypoxia plays a crucial role in the tumorigenesis of PPGLs, and therefore PPGLs are also known as metabolic diseases. However, the interplay between VHL/HIF-mediated pseudohypoxia and metabolic disorder in PPGLs cells is not well-defined. In this review, we will first discuss the VHL/HIF axis and genetic alterations in this axis. Then, we will dissect the underlying mechanisms in VHL/HIF axis-driven PPGL pathogenesis, with special attention paid to the interplay between the VHL/HIF axis and cancer cell metabolism. Finally, we will summarize the currently available compounds/drugs targeting this axis which could be potentially used as PPGLs treatment, as well as their underlying pharmacological mechanisms. The overall goal of this review is to better understand the role of VHL/HIF axis in PPGLs development, to establish more accurate tools in PPGLs diagnosis, and to pave the road toward efficacious therapeutics against metastatic PPGLs.

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Metabolic Alterations in Patients with Pheochromocytoma

Cited by 24 publications

References 69 publications

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients

Impaired Glucose Metabolism in People with Extremely Elevated High-Density Lipoprotein Cholesterol and Low Alcohol Consumption: Results of the Kanagawa Investigation of Total Checkup Data from the National Database-3 (KITCHEN-3)

The VHL/HIF Axis in the Development and Treatment of Pheochromocytoma/Paraganglioma

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