Dihydroxyphenylglycol in Pheochromocytoma: Its Diagnostic Use for Norepinephrine Dominant Tumor

To discern whether the 3,4-dihydroxyphenylglycol produced in adrenal medulla is associated with altered urinary excretion, we compared the tissue and urinary levels of this catecholamine metabolite, epinephrine and norepinephrine in 23 patients with pheochromocytoma and 26 subjects with renal cell carcinoma.Tissue and urine concentrations of dihydroxyphenylglycol, epinephrine and norepinephrine were determined by catechol-O-methyl-transferase-based radioenzymatic method and high performance liquid chromatography with electrochemical detection.Contents of dihydroxyphenylglycol, epinephrine and norepinephrine in pheochromocytomas were higher than those in normal adrenal medullae. Removal of pheochromocytomas lowered urinary excretion of these catecholamines and dihydroxyphenylglycol. Norepinephrine content correlated closely with dihydroxyphenylglycol content in normal adrenal medullae and pheochromocytomas but not with epinephrine content in either tissue. Contents of norepinephrine and dihydroxyphenylglycol correlated significantly with urinary norepinephrine excretion and dihydroxyphenylglycol excretion in patients with pheochromocytoma but not in subjects with renal cell carcinoma. The norepinephrine-to-dihydroxyphenylglycol ratio in a 24-hour preoperative urine collection from patients with pheochromocytoma was higher than that from subjects with renal cell carcinoma, which was almost similar to that of epinephrine dominant pheochromocytomas.Our study suggests that dihydroxyphenylglycol in urine in subjects with renal cell carcinoma is predominantly of a neuronal origin and urinary dihydroxyphenylglycol in patients with pheochromocytoma is of tumor origin. A high level of norepinephrine-to-dihydroxyphenylglycol ratio in urine can be used to determine the diagnosis of the norepinephrine dominant type pheochromocytoma. Measurement of at least a few markers is preferable for precise biochemical diagnosis of pheochromocytoma.