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Prostaglandin and catecholamine concentrations were estimated in tumour tissues taken from four phaeochromcytomas and five other neural-crest tumours. Prostaglandins were found to be present in tumours both associated and non-associated with chronic diarrhoea. Prostaglandin F, as well as catecholamine, concentrations were higher in phaeochromocytomas than in other tumours. The hypothesis has been made that while prostaglandins do not reach arterial circulation to give rise to pharmacological effects, such as chronic diarrhoea, prostaglandins F present in phaeochromocytomas may contribute to a higher catecholamine synthesis and/or release, resulting in a higher incidence of hypertension associated with these tumours.

Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.

In order to develop an immunoradiometric assay for human neuropeptide (hNPY), a recently discovered and potent vasoconstrictor 36-amino-acid peptide, we used hNPY and some of its subpeptides to prepare monoclonal anti-NPY antibodies. Two monoclonal antibodies with high affinity for hNPY, that is affinity constants in the range of 10(10) mol/L-1, which respectively, reacted with the 9-18 portion and the 32-36 portion of hNPY were used in the immunoradiometric system. The assay was highly specific, NPY-related peptides such as pancreatic polypeptide and peptide YY not being detected. The lower limit of sensitivity was 0.5 pmol/L. In 303 normal subjects, plasma NPY concentrations were less than 0.5 pmol/L in 67%, 0.5 to 5.0 pmol/L in 25% and 5.1 to 30 pmol/L in the remaining 8%. A value of 7.5 pmol/L (95th percentile value in the normal group) was considered as the upper limit of normal. Among 111 patients with various neuroendocrine tumors, elevated plasma NPY concentrations were found in patients with pheochromocytomas and neuroblastomas, the highest plasma levels being found in patients with malignant pheochromocytomas. We conclude that patients with neuroendocrine tumors, especially secreting and or malignant tumors of the sympathochromaffin system, often have elevated plasma NPY concentrations.