Catecholamine Metabolism in Pheochromocytoma and Normal Adrenal Medullae

Nakada, Teruhiro; Furuta, H; Katayama, Takashi

doi:10.1016/s0022-5347(17)42041-6

Cited by 33 publications

(12 citation statements)

References 15 publications

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“…This was ruled out as this type of feedback has not been described in phaeochromocytoma in which secretion and liberation of catecholamines appear to be out of control. 10 We assumed it to have been due to saturation of a-1 receptors by urapidil, which would lead to an increase in the amounts of circulating norepinephrine. This increase in the area under the curve of norepinephrine was interpreted as a pharmacological validation of optimal blockade of a-1 receptors.…”

Section: Discussionmentioning

confidence: 99%

Preparation for surgery of phaeochromocytoma by blockade of α-adrenergic receptors with urapidil: what dose?

Gosse

Tauzin-Fin

et al. 2009

J Hum Hypertens

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The preparation for phaeochromocytoma surgery is a matter of debate. Pre-operative blockade of a-1 receptors is increasingly employed in an attempt to reduce the risk of hypertensive episodes, especially during manipulation of the tumour. In this study, we compared the interest of an almost complete blockade of these receptors by high doses of urapidil in comparison with that of moderate doses of this drug. The study was conducted in two consecutive series of 18 patients, the first treated by a moderate dose, and the second by the highest dose tolerated by the patient. The two groups were comparable in other respects. All patients were operated under laparoscopy by the same surgeon and managed by the same anaesthetist using the same protocol. The number of hypertensive peaks was significantly reduced using the high dose of urapidil, with no more hypotensive episodes after tumour removal in this group. The area under the curve of norepinephrine levels as a function of time was significantly larger with the high doses of urapidil, arguing in favour of a more complete blockade of a-1 receptors. Our findings indicate the value of aggressive blockade of a-1 receptors in preparation for surgery of phaeochromocytoma.

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Section: Discussionmentioning

confidence: 99%

Preparation for surgery of phaeochromocytoma by blockade of α-adrenergic receptors with urapidil: what dose?

Gosse

Tauzin-Fin

et al. 2009

J Hum Hypertens

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“…Nakada et al (19) reported that pheochromocytomas contained a significantly larger amount of catecholamines and greater tyrosine hydroxylase activity than did normal adrenal medullas. Iwase et al (20) also observed high tyrosine hydroxylase activity in pheochromocytomas.…”

Section: Discussionmentioning

confidence: 99%

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas

Isobe

Nakai²,

Yukimasa³

et al. 1998

European Journal of Endocrinology

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Objective: To understand the molecular mechanisms by which catecholamine synthesis is controlled in pheochromocytomas -tumors that synthesize and release catecholamines, which are related to various clinical manifestations of the condition. Methods: We measured the concentrations of mRNA coding for the catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), dopamine b-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) and for the catecholamine contents in 12 pheochromocytomas and 12 normal adrenal medullas. Results: The mean content of total catecholamine and the b-actin mRNA expression in the pheochromocytomas were almost the same as those in the normal adrenal medullas. However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsible for the difference in the proportions of catecholamines between pheochromocytomas and normal adrenal medullas. The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA expressions correlated with the contents of total catecholamine in the tumors (r=0.964, P<0.0001). Conclusions: These findings indicate that catecholamine production in pheochromocytomas is primarily controlled by the level of gene expression.

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“…Activities of tyrosine hydroxylase, aromatic L-amino acid decarboxylase and dopamine ß-hydroxylase are generally very high in these tumors, providing the basis for catecholamine overproduction in these tumors (62-64). Among different pheochromocytomas, activities of tyrosine hydroxylase are high in tumors from patients with MEN2 and low in those from von Hippel-Lindau (VHL) patients or patients with non-functional tumors (57, 58).…”

Section: Pheochromocytoma: a Catecholamine Disordermentioning

confidence: 99%

Phaeochromocytoma: a catecholamine and oxidative stress disorder

Pacák¹

2011

endo

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The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla — an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called “attacks” or “spells”. Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto-oncogene activation, tumor suppressor gene inactivation, DNA damage, and genomic instability. Since the mitochondria serves as the main source of prooxidants, any mitochondrial impairment leads to severe oxidative stress, a major outcome of which is tumor development. In terms of cancer pathogenesis, pheochromocytomas and paragangliomas represent tumors where the oxidative phosphorylation defect due to the mutation of succinate dehydrogenase is the cause, not a consequence, of tumor development. Any succinate dehydrogenase pathogenic mutation results in the shift from oxidative phosphorylation to aerobic glycolysis in the cytoplasm (also called anaerobic glycolysis if hypoxia is the main cause of such a shift). This phenomenon, also called the Warburg effect, is well demonstrated by a positive [18F]-fluorodeoxyglycose positron emission tomography scan. Microarray studies, genome-wide association studies, proteomics and protein arrays, metabolomics, transcriptomics, and bioinformatics approaches will remain powerful tools to further uncover the pathogenesis of t...

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Catecholamine Metabolism in Pheochromocytoma and Normal Adrenal Medullae

Cited by 33 publications

References 15 publications

Preparation for surgery of phaeochromocytoma by blockade of α-adrenergic receptors with urapidil: what dose?

Preparation for surgery of phaeochromocytoma by blockade of α-adrenergic receptors with urapidil: what dose?

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas

Phaeochromocytoma: a catecholamine and oxidative stress disorder

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