Manger, William M.

Abstract Comparative studies reveal that the ethylenediamine and the trihydroxyindole method when employed as suggested are suitable for assessing sympatho-adrenal activation under various stressful conditions that are accompanied by release of catecholamines into the circulation. Both methods are very accurate in quantitating epinephrine or norepinephrine that has been added to plasma or whole blood, although recovery from blood is less, owing mainly to some association of catecholamines with formed elements, primarily erythrocytes. Use of sodium thiosulfate in the ethylenediamine procedure minimizes association of catecholamines with formed elements. If blood samples are cooled in ice water when collected, association of catecholamines with blood cells can be further reduced. In the trihydroxyindole method, unless tubes containing blood samples are immediately immersed in ice water, a significant amount of catecholamines will disappear from plasma, because of this association of catecholamines with cells.

A fluorometric method was used to quantitate plasma epinephrine and norepinephrine during hemorrhagic and anaphylactic shock in healthy adult dogs anesthetized with pentobarbital. Arterial plasma was analyzed before and after hemorrhage in four dogs. Loss of approximately 18% of blood volume through rapid arterial bleeding caused no remarkable change in pressor amines. Loss of approximately one-third of the total blood volume decreased the mean arterial pressure by a range of 56–81% and invariably caused increased concentration of plasma pressor amines. The average concentration of epinephrine increased from 1.0 to 7.8 µg/1. of plasma, and that of norepinephrine increased from 2.5 to 3.6 µg. Additional bleeding caused further increase of plasma pressor amines. Seven dogs were given egg white intravenously to sensitize them. Subsequently, whenever a severe reaction (hypotension, bradycardia and respiratory depression) resulted from intravenous administration of egg white, venous plasma pressor amines increased. The average concentration of epinephrine increased from 0.7 to 7.7 µg/1. of plasma; norepinephrine increased in three dogs but remained unchanged or decreased in the remaining animals. Without a preceding ‘shock’ reaction, change in concentration of epinephrine-like substance was unremarkable. Intravenous administration of 1 mg of histamine base produced hypotension and usually slight increase of plasma pressor amines.

Fluorescent quantitation of epinephrine and norepinephrine in plasma of patients suspected of having pheochromocytomas is of considerable diagnostic value. The concentrations of these pressor amines in normal subjects, patients with various diseases with and without hypertension, and 13 patients with pheochromocytomas are reported. In all patients with pheochromocytomas and sustained hypertension the concentrations of pressor amines were significantly elevated. However, in patients with paroxysmal hypertension secondary to pheochromocytomas the pressor amine concentrations may be unelevated when the blood pressures are normal. In this latter group provocative tests with intravenous histamine are indicated to induce hypertension prior to quantitating pressor amines.

Abstract Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th–18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies.