Value of the plasma norepinephrine/3,4-dihydroxyphenylglycol ratio for the diagnosis of pheochromocytoma

Abstract

Purpose: The purpose of this study was to assess whether the plasma norepinephrine/3,4-dihydroxyphenylglycol ratio (NE/DHPG) is of diagnostic relevance for patients with a pheochromocytoma.

Subjects and methods: In 18 patients with a histologically proven pheochromocytoma and in nine patients with congestive heart failure, plasma levels of NE, epinephrine (EPI), and DHPG (radioenzymatic method) were determined after 20 minutes of supine rest. In 10 healthy subjects, the plasma catecholamine responses to active standing (5 minutes) and mental arithmetic (5 minutes) were measured. From the plasma NE and DHPG levels, the plasma NE/DHPG ratio was calculated. In order to analyze whether NE or EPI was the major secreted catecholamine, the patients with a pheochromocytoma were divided into two groups based on the increase of plasma NE above normal relative to that of EPI: Group 1 included patients with increased plasma NE or increased plasma NE and EPI. Group 2 included patients with increased plasma EPI in combination with a nearly normal NE.

Results: Both active standing and mental arithmetic increased the plasma NE/DHPG ratio by 105% and 13.6%, respectively, but in all subjects the ratio did not exceed 1.0. Patients with heart failure demonstrated a threefold higher plasma NE/DHPG ratio than did healthy subjects, and the ratio also did not exceed 1.0. The plasma NE/DHPG ratio was about seven to eight times higher in Group 1 (mean: 1.62, range: 0.81 to 2.84) than in Group 2 (mean: 0.24, range: 0.12 to 0.68). Nearly all patients in Group 1 had a NE/DHPG ratio that was higher than 1.0. In contrast, five of six samples of Group 2 demonstrated a NE/DHPG ratio within the normal range. The calculated positive and negative predictive values of a basal plasma catecholamine level were higher than that for the plasma NE/DHPG ratio.

Conclusions: In contrast to earlier reports, a normal plasma NE/DHPG ratio does not exclude the presence of a pheochromocytoma. In patients with a pheochromocytoma that produces EPI predominantly, this ratio may be normal. On the other hand, in patients with congestive heart failure, the plasma NE/DHPG ratio is increased, although there is no clear overlap with values of patients with a pheochromocytoma. Although the prevalence of pure EPI-producing pheochromocytomas is low, the plasma NE/DHPG ratio should be used with caution in the diagnostic evaluation of patients with a suspected pheochromocytoma.