Urinary Excretion of Norepinephrine, Epinephrine and 3-Methoxy-4-Hydroxymandelic Acid by Children With Neuro-Blastoma*†

Voorhess, Mary L.; Gardner, Lytt I.

doi:10.1210/jcem-21-3-321

Cited by 69 publications

(15 citation statements)

References 19 publications

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“…The case of Kraupp, Stormann, and Bernheimer (19) is a well-documented example of this situation. In children with neuroblastoma, ratios of urinary NE to VMA are extremely variable and frequently very low (27), suggesting that extensive metabolism of NE occurs in these tumors as well as in pheochromocytoma; in the case of neuroblastoma, the VMA excretion is usually the more valuable diagnostic aid (28).…”

Section: Resultsmentioning

confidence: 99%

Turnover and Metabolism of Catecholamines in Patients with Pheochromocytoma*

Crout¹,

Sjoerdsma²

1964

J. Clin. Invest.

189

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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...

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Section: Resultsmentioning

confidence: 99%

Turnover and Metabolism of Catecholamines in Patients with Pheochromocytoma*

Crout¹,

Sjoerdsma²

1964

J. Clin. Invest.

189

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“…Physiological changes brought about by the malignancy either do not correlate consistently with the presence of tumour or are not suitable for diagnosis of "minimal residual disease" (Kemshead and Black, 1980), e.g. elevated urinary catecholamines (Voorhess and Gardner, 1961), serum catecholamines (Nakano et al, 1976) and chromosomal aberrations (Biedler et al, 1978). Rabbit antisera to human neuroblastoma have been described Casper et al, 1977), but these reagents suffer from low titre after extensive absorption to make them specific.…”

mentioning

confidence: 99%

Monoclonal antibody to ganglioside gq discriminates between haemopoietic cells and infiltrating neuroblastoma tumour cells in bone marrow

Kemshead

Walsh

Pritchard

et al. 1981

Intl Journal of Cancer

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An immunological approach has been sought for the identification of minimal metastatic spread of neuroblastoma to bone marrow. Here we describe the reactivity of the monoclonal antibody A2B5 to human neuroblastoma cell lines and fresh tumour tissue. This reagent, raised against chick retinal cells, reacts with all human neuroblastoma lines assayed although quantitative differences in antigenic expression exist between cultures. Analysis of tumour cells in heavily infiltrated bone marrow aspirates indicates that only 70% of the samples reacted with A2B5, suggesting that the heterogeneity seen in the expression of antigen on cell lines is paralleled in fresh tumour material. A2B5 showed no reactivity to either a panel of human leukaemic cell lines or normal human bone marrow, although reactivity to an occasional leukaemic marrow aspirate was detected. We suggest that A2B5 could form part of a panel of monoclonal reagents necessary for detecting metastatic spread of all neuroblastoma cells to bone marrow. Such a group of reagents may be useful therapeutically in a programmed of autologous bone marrow transplantation for the removal of tumour cells prior to reinfusion of haemopoietic cells to patients receiving high-dose chemotherapy.

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“…Several workers have used the biochemical activity of the tumour, as reflected by the urinary excretion of catecholamines and their metabolites, to chart the clinical progress of the patient (Greenberg and Gardner, 1960;von Studnitz, 1960;von Studnitz et al, 1963;Smellie and Sandler, 1961;Voorhess andGardner, 1961, 1962a, b;Bettex and Kaser, 1962;Kontras, 1962;Young, Steiker, Bongiovanni, Koop and Eberlein, 1963;Sourkes et al, 1963;Rosenstein and Engelman, 1963;Williams and Greer, 1963). Williams andGreer (1962, 1963) have pointed out from their own experiences and from a study of the literature that the measurement of HVA, the major metabolite of dopamine, and of VMA, the major metabolite of noradrenaline, provide sufficient information to make a diagnosis in most cases of this secreting tumour.…”

Section: Discussionmentioning

confidence: 99%