The diagnosis of pheochromocytoma by determination of urinary 3-methoxy-4-hydroxymandelic acid.

In 1957, Armstrong, McMillan and Shaw demonstrated a metabolite of epinephrine (E) and norepinephrine (NE) in normal human urine (2, 3). This substance, 3-methoxy,4-hydroxymandelic acid (VMA, for vanillylmandelic acid), was excreted in abnormally large amounts in three patients with pheochromocytomas (3). Recent studies of sympathomimetic amine metabolism (Figure 1) (4-7) suggested that the urinary excretion of the degradation products of E and NE, such as their 3-methylated derivatives (M and NM respectively) and VMA, might exceed E and NE excretion by some 10or 20-fold. The diagnosis of pheochromocytoma might therefore be facilitated by analysis of urine for these phenolic compounds. Armstrong, Shaw and Wall's chromatographic technique for determination of urinary VMA (8, 9) was modified and used for the quantitative determination of VMA excretion in the urines of