Biochemical Studies of Catecholamine in Patients with Neuroblastoma

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It has been well known that both pheochromocytoma and neuroblastoma developed from primitive elements of the neural crest. In 1957, Mason et al. first described an increased catecholamine excretion in an infant with neuroblastoma. Although many biochemical studies have been reported on patients with pheochromocytoma, only a few papers on neuroblastoma have appeared. Since the most significant clinical features in neuroblastoma were anemia, skin nodules, palpable large tumors in the abdomen and cachexy, the biochemical studies on catecholamine metabolism in this neural tumor might have been overlooked. The purpose of this paper is to report on abnormal excretion patterns of urinary catecholamines and their metabolites in children with neuroblastoma and on the usefulness of one spot test which was developed previously in this laboratory for screening of neuroblastoma.<BR>There were 7 cases of neuroblastoma studied. Diagnosis was established by histologic identification of biopsy, autopsy and surgical specimens of the tumor.<BR>Twenty-four hour urine was collected under acidic condition. Adrenaline (A) and noradrenaline (NA) were measured by a modification of the method of Euler et al. Dopamine was determined by the method of Drujan et al. Metadrenaline and normet-adrenaline (3-methoxyamine, MA) were determined by the method of Yoshinaga et al. Vanillylmandelic acid (VMA) was estimated by the modification of the method of Studnitz et al. Abnormally high catecholamine excretion was observed in 4 of the 7 patients. Dopamine was increased in 2 of the 3 patients estimated. So far as tested, MA was significantly elevated in all 4 patients. High excretion of VMA was found in 6 of the 7 patients, as shown in TABLE I. From these data, neuroblastoma could be sub-classified into the following various types: (1) elevated excretion of both catecholamine and metabolite ; (2) elevated excretion of catecholamine with nearly normal metabolite ; (3) nearly normal catecholamine excretion with increased excretionof metabolite and (4) normal excretion of both catecholamine and metabolite. A demonstrable abnormality of catecholamine metabolism was also found in these patients when excretion ratio of catecholamine: MA: VMA was compared with that in urine from normal subjects, patients with pheochromocytoma and subjects who received noradrenaline infusion. The ratio in normal subjects was 1: 10: 140, while in patients with neuroblastoma was 1: 190: 1, 040. Almost the same ratio was obtained in both urine specimens from patients with pheochromocytoma and from subjects during noradrenaline infusion (Fig. 1, 2).<BR>The date were not yet sufficient to explain why different patterns of catecholamine and metabolite appeared in the urine from these children. The urinary excretion of MA and VMA exceeded that of catecholamine by 100 to 2, 000 times. Therefore, it appeared that metabolism of catecholamine in these children might be performed in a different manner from the usual one, which would lead to an excessive formation of methylated products, MA and VMA. Possible explanation might be that the metabolic activity in tumor tissue or non-tumor peripheral tissue was abnormally increased.<BR>One spot test for qualitative detection of increased methylated products of catecholamine was performed in these 7 neuroblastomas. Since 1961, the test has been routinely used in our clinic for screening of pheochromocytoma, neuroblastoma and argentaffinoma. Up to the present, 18 more cases of neuroblastoma were subjected to this test in other medical institutions. Positive results were reported in 22 of these 25 patients (83%). It is our hope that this simple test be used more widely for screening of these amine-producing tumor.

Biochemical Studies of Catecholamine in Patients with Neuroblastoma

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