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Endocrine and Neuroendocrine Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Natasha Shrikrishnapalasuriyar, P.N. Plowman, Márta Korbonits, Ashley B. Grossman
Biochemical diagnosis is based on increased catecholamine metabolites. Plasma or urinary fractionated metanephrines (normetanephrine and metanephrine) are highly sensitive and form the basis for specific screening tests that detect secretory pheochromocytomas and paragangliomas: Plasma 3-methoxytyramine, a metabolite of dopamine, is used as a potential marker of malignancy.66
Involvement of Dopamine with Various Cancers
Published in Nira Ben-Jonathan, Dopamine, 2020
Diagnosis is established by tumor biopsy and by urinary catecholamines, which are elevated in about 90% of cases. Urinary catecholamines and their metabolites, i.e., DA, homovanillic acid (HVA), and 4-hydroxy-3-methoxymandelic acid (HMMA) are established tests that are used for two purposes: (1) to support the diagnosis of NBL disease, and (2) to monitor disease activity following treatment [106]. Both free and total 3-methoxytyramine (MTY), the O-methylated product of DA, were elevated in all patients with untreated NBL disease, leading the authors to suggest that MTY is an especially good biomarker for differentiating treated patients with advanced or residual disease from controls. The main drivers of NBL formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. In the research arena, neuroblastoma-derived cell lines such as SH-SY5Y, SK-N-MC, SK-N-SH, and N2A have been extensively used as cellular models to investigate multiple aspects of DA homeostasis, including biosynthesis, reuptake, receptor expression, mechanism of action, and drug effects.
Genetic Disorders of the Autonomic Nervous System
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
Noradrenaline metabolites have been low or absent in plasma, urine and cerebrospinal fluid (CSF). Conversely, dopamine metabolites such as homovanillic acid and 3-methoxytyramine are raised. Determination of whether or not noradrenaline exists at all in patients with DBH deficiency must await further investigations and improvements in assay methodology. A low, but apparently detectable, level of vanillylmandelic acid was found in the urine of three patients (Robertson et al., 1986a; Mathiaset al., 1990), and a low, but detectable, level of 3-methoxy-4-hydroxyphenylglycol was found in the CSF of another patient (Manin’t Veldet al., 1987a). In other patients, these metabolites have been beneath the limits of detection of the assay. Whether these reflect genuine differences in pathology or the limitations of the respective assays remains to be seen.
Alpha-synuclein in Parkinson's disease: a villain or tragic hero? A critical view of the formation of α-synuclein aggregates induced by dopamine metabolites and viral infection
Published in Expert Review of Neurotherapeutics, 2023
Phelippe Carmo-Gonçalves, Eduardo Coelho-Cerqueira, Vanderlei de Araujo Lima, Cristian Follmer
The enzymatic degradation of DA is done by the enzymes monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). COMT, found predominantly in glial cells, metabolizes DA to 3-methoxytyramine, which is then converted to homovanillic acid. MAO is found in neurons, glial cells and astrocytes, where it catalyzes the oxidation of DA to the toxic aldehyde DOPAL, with hydrogen peroxide as a byproduct. DOPAL is then preferentially oxidized by the enzyme aldehyde dehydrogenase (ALDH1A1) forming 3,4-dihydroxyphenylacetic acid (DOPAC) or minority reduced to 3,4-dihydroxyphenylethanol (DOPET) by the enzyme alcohol dehydrogenase [48,49]. MAO inhibitors are part of the therapeutic strategy used in the symptomatic treatment of PD, since the inhibition of the enzyme prevents the degradation of DA. The catecholaldehyde hypothesis for the pathogenesis of PD suggests that DOPAL occupies a central position in the toxic events that lead to the degeneration of dopaminergic neurons [43,50]. This hypothesis is reinforced by the fact that aging was associated with an increased MAO activity [51], while ALDH activity decreased by 70% in PD putamen [52], which could contribute to an elevation of DOPAL levels (Figure 1). DOPAL, at a nanomolar range, is found to be sufficient to initiate apoptosis by activation of the mitochondrial permeability transition (mPT), which leads to mitochondrial dysfunction. DA, even at higher concentrations, is not able to cause mPT [53].
Pheochromocytoma with Acute Non-cardiac Pulmonary Edema: A Report of One Case and the Review of Literature
Published in Cancer Investigation, 2021
Yuan Liu, Ning Wang, Shi Li, Ling Jiang, Chunfang Liu, Jian Xu, Huadong He
Abnormal cortisol rhythm was then occurred. Cortisol was 6.30 µg/dl at 24:00 midnight. There was no obvious abnormality of the cortisol level at 8:00 a.m. and 16:00 p.m. Plasma metanephrines (3 items) included 3-methoxytyramine (0.22 nmol/L), methoxyepinephrine (1.7 nmol/L), methoxynorepinephrine (6.35 nmol/L). New type α 1 receptor blocker, doxazosin, was given before operation to prevent increased paroxysmal blood pressure during adrenal tumor operation. On January 29, 2018, laparoscopic adrenalectomy was performed after blood pressure was monitored for two weeks. During the operation, a spherical tumor of about 6 × 6 cm was found in the left adrenal region, with abundant blood supply, capsule and slight adhesion with surrounding tissues. The blood pressure of the patient was increased after touching the tumor. The tumor submitted for examination was nodular and had been cut with the volume of 4 × 3 × 3 cm, which was actually golden yellow. Hematoxylin-eosin (HE) staining showed pheochromocytoma. Immunohistochemistry showed CgA (+), S-100 (+), NSE (+), Melan-A (-), Syn (+), Ki-67 (+ < 1%)) (Figure 4). The patient recovered well after operation, and the incision healed I/A. After three years of follow-up, the patient's condition was stable, and there were no symptoms such as respiratory failure, shock, heart failure and tumor recurrence.
Study of stability and interference for catecholamines and metanephrines, 3-methoxytyramine: key point of an accurate diagnosis for pheochromocytoma and paraganglioma
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2021
Kaijuan Wang, Xiaojing Gao, Wei Zhang, Nian Sun, Lan Xie, Hongying Cong, Yutong Guo, Xiaocui Shi, Zhou Zhou
Chemically, catecholamines are monoamines linked to a benzene ring with two vicinal hydroxyl groups. The ring structure makes the compounds sensitive to light and easily oxidized, the stability of catecholamines and their metabolites in plasma has attracted much attention. However, there are some controversies, D'Alesandro [5] and Pettersson J [6] declared that EPI and NE are stable at 24 °C/20 °C for 24 h/22 h regardless of whether glutathione or sodium metabisulphite is added to the sample. However, Boomsma F [7] mentioned in his paper, blood is generally collected into tubes containing an anticoagulant and antioxidant (glutathione, sodium metabisulfite, or ascorbic acid), both Boomsma F and Carruthers M [8] believed that a delay in centrifugation of blood led to an immediate decay in measured plasma catecholamines, these studies are getting aged. In recent years, there are also studies on sample storage and transport, most of them focus on metanephrine (MN) and normetanephrine (NMN) [9,10], a few studies focus on EPI and NE. Although there is compelling evidence that plasma free metanephrines (MNs: MN and NMN) are superior to catecholamines for diagnosis of PPGLs, the determination of plasma EPI, NE, DA continues to be required by clinicians, in addition, since DA and 3-methoxytyramine (3-MT) may be markers of dopamine-producing tumors, storage and transport conditions of them should also be evaluated.