Turnover and Metabolism of Catecholamines in Patients with Pheochromocytoma*

Abstract

When norepinephrine (NE) or epinephrine (E) is infused into a human subject, all but about 4% of the amine is metabolized to urinary 0-methylated and deaminated metabolites (1-4).The percentage excreted as each metabolite is fairly constant even in different individuals (1)(2)(3). This is in distinct contrast to the situation in patients with pheochromocytoma. In this disease patients with similar excretion values for free catecholamines may show up to tenfold differences in their excretion rates of metabolites (5). This implies that a pheochromocytoma may not be simply an endogenous source of circulating NE and E; catecholamine metabolism in these patients is more complex than traditional views would suggest. This paper describes a) the urinary excretion rates of NE and E and of their two major metabolites in 24 patients with pheochromocytoma, b) the NE and E content of the tumors of 23 of these patients, and c) the normetanephrine (NMN) plus metanephrine (MN) content of 9 tumors. An analysis of these data reveals certain correlations, not previously emphasized, between the size of the tumor, the rate of turnover of catecholamines within the tumor, and the pattern of catecholamine metabolites in the urine. We concluded that in some pheochromocytomas much of the catecholamine synthesized is degraded directly in the tumor before it ever reaches the circulation. This process may partially "protect" the patient from the cardiovascular effects of his tumor and thereby modify the clinical course of the disease.Materials and Methods Twenty-four hour urine specimens were collected in glass bottles containing 10 to 15 ml 6 N hydrochloric acid and were stored at -200 C or at 00 C. Portions of tumor were frozen on removal and stored at -200 C until the time of assay. Urine specimens and tumor samples shipped from outside hospitals were kept frozen on dry ice en route. Free urinary NE and E were determined fluorimetrically by a modification of the trihydroxyindole method (6). The mean recovery of NE plus E was 87%o; the results were not corrected for this small loss. Total NMN plus MN was determined by a modification of Pisano's method (5); no correction was made for an average recovery of 84%. This method measures the combined total of free and conjugated NMN plus MN but does not distinguish between these two 0-methylated amines. Urinary 3-methoxy-4-hydroxymandelic acid (vanilmandelic acid, VMA) was measured by the method of Pisano, Crout, and Abraham (7) ; the recovery in this procedure is quantitative.Tumors were assayed for NE and E by homogenizing 0.5 to 1.0 g of tissue in 10 ml cold 5% trichloroacetic acid, centrifuging to obtain a clear supernatant solution, and assaying this extract fluorimetrically. The tumor content of NMN plus MN was determined by preparing a 5% trichloroacetic acid extract as described above, adjusting its pH to 8.4 with 2 N ammonium hydroxide, and passing it over a 1.2-X 6-cm column of alumina to remove catecholamines. The effluent was then brought to pH 6.0 with 1 N acetic acid and carried th...

Frequent incidental discovery of phaeochromocytoma: data from a German cohort of 201 phaeochromocytoma

“…Interestingly, 6.1% of our phaeochromocytoma patients were normotensive, emphasising that the absence of hypertension does not rule out the presence of a cataecholamine-producing tumour that might result in life-threatening situations (15). One explanation may be that tumour-dependent hormone production may remain silent for a long period of time, because active cataecholamines can be converted into biologically inactive metanephrines by cataechol-Omethyltransferase within the tumour (8,16,17). Owing to the rare occurrence, the often unspecific signs and symptoms, and the low sensitivity of any symptoms and the diagnosis of phaeochromocytoma may be delayed.…”

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

“…The longer half-time for the decline of plasma NE than of L-DOPS would tend to favor the vesicular site. Consistent with this source, the initial decline of plasma NE in MSA patients corresponds roughly to the half-time of NE stored in vesicles in sympathetic nerves (13,44,94).…”

DIAGNOSIS OF ENDOCRINE DISEASE: Biochemical diagnosis of phaeochromocytoma and paraganglioma

“…Nowadays, it is well established that measurements of urinary and plasma catecholamines are insufficiently reliable because catecholamine secretion in PPGLs is often episodic or even negligible in asymptomatic patients. This higher diagnostic accuracy of metanephrines can be attributed to continuous intratumoural production and secretion of metanephrines into the circulatory compartment (21,33,34). This secretion is independent of highly variable catecholamine release caused by the tumour or by sympathoadrenal excitation (35).…”