Biochemical and Clinical Manifestations of Dopamine-Producing Paragangliomas: Utility of Plasma Methoxytyramine

Abstract

Measurements of plasma-free normetanephrine and metanephrine provide a sensitive test for diagnosis of pheochromocytoma but may fail to detect tumors that produce predominantly dopamine. Such tumors are extremely rare, usually found as extraadrenal paragangliomas. This report describes measurements of plasma concentrations of free methoxytyramine, the O-methylated metabolite of dopamine, in 120 patients with catecholamine-producing tumors, including nine with extraadrenal paragangliomas secreting predominantly dopamine. In seven of these nine patients, tumors were found incidentally or secondary to the space-occupying complications of the lesions. Plasma concentrations of free methoxytyramine and dopamine were increased in all nine patients, including two with normal plasma and urinary normetanephrine and metanephrine and normal urinary outputs of dopamine. Relative increases above normal for plasma methoxytyramine (104-fold) and dopamine (56-fold) were much greater (P < 0.001) than those for urinary dopamine (3-fold). Insensitivity of the latter for identification of dopamine-secreting tumors was due to dependence of the urinary amine on renal extraction and decarboxylation of circulating 3,4-dihydroxyphenylalanine. Measurements of plasma-free methoxytyramine, in addition to normetanephrine and metanephrine, are unlikely to improve diagnosis of pheochromocytomas in hypertensive patients with symptoms of catecholamine excess but may be useful in selected patients for identification of tumors that produce predominantly dopamine.

Dopamine-secreting Carotid Body Paragangliomas-Biochemical Control with Radiotherapy

“…This recommendation has also been suggested by van der Mey et al for the management of carotid body tumors (16). Compared to urinary dopamine, plasma methoxytyramine (an Omethylated metabolite of dopamine) has been reported to be a better marker for tumors that secrete predominantly dopamine (2).…”

“…Elevated plasma and/or urinary dopamine are more often associated with malignant than benign pheochromocytomas (2,17,18). Increased excretion of dopamine was shown to predict malignant potential in preoperative patients with apparently non-metastatic paragangliomas (19).…”

“…Highly vascular paragangliomas can arise from any of these tissues. Paragangliomas which produce catecholamines in amounts sufficient to produce signs and symptoms or positive results on biochemical testing are uncommon (2). Tumors that exclusively or predominantly secrete dopamine are even rarer.…”

“…Tumors that exclusively or predominantly secrete dopamine are even rarer. Such tumors usually have an extra-adrenal location and are often malignant with multifocal or metastatic disease (2,3).…”

Personalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinology

“…Недавно проведенные исследования по-зволили предположить, что 3-метокситир-амин может рассматриваться не только как биохимический маркер допамин-продуци-рующих опухолей [57], но и как индикатор злокачественности опухоли. У пациентов с биохимически "молчащими" опухолями определение уровня хромогранина А как универсального биомаркера нейроэндо-кринных опухолей является важным вспомо-гательным тестом [58].…”