CIRCULATING DIHYDROXYPHENYLGLYCOL AND NOREPINEPHRINE CONCENTRATIONS DURING SYMPATHETIC NERVOUS-SYSTEM ACTIVATION IN PATIENTS WITH PHEOCHROMOCYTOMA

Although increased plasma norepinephrine (NE) concentrations mediate v asoconstriction during episodic hypertension and hypertensive crises i n patients with pheochromocytoma (Pheo), the precise origin of this ci rculating NE (tumor or sympathetic nerves) is not known. Dihydroxyphen ylglycol (DHPG), a deaminated metabolite of NE, is formed principally in sympathetic nerve endings. Under basal conditions, plasma NE and DH PG concentrations correlate closely, and during sympathetic nervous sy stem activation, both plasma NE and DHPG concentrations increase. This observation suggests that plasma DHPG concentrations may reflect the source of circulating NE (tumor or sympathetic nerves) during hyperten sive episodes in patients with Pheo. Plasma NE and DHPG concentrations were measured simultaneously, and the NE/DHPG ratio was calculated in seven patients with Pheo during 20 min of sympathetic nervous system activation (treadmill exercise) before and after surgical resection of the tumor. Age- and sex-matched normal subjects were also studied. Ex ercise resulted in a significant increase in plasma NE and DHPG concen trations in patients with Pheo and in normal subjects (Pheo: basal NE, 1827 +/- 639; peak NE, 3016 +/- 769 pg/mL (P = 0.02); normal subjects : basal NE, 266 +/- 27; peak NE, 1166 +/- 197 pg/mL (P = 0.01); Pheo: basal DHPG, 1521 +/- 280; peak DHPG, 2313 +/- 252 pg/mL (P = 0.007); n ormal subjects: basal DHPG, 870 +/- 50; peak DHPG, 1630 +/- 180 pg/mL (P = 0.01)]. The NE/DHPG ratio increased with exercise in normal subje cts (basal, 0.30 +/- 0.02; peak, 0.83 +/- 12; P = 0.005), but did not change in patients with Pheo (basal, 1.22 +/- 0.32; peak, 1.54 +/- 0.2 7). Exercise also increased plasma NE and DHPG concentrations and the NE/DHPG ratio in five patients studied after surgical resection of the tumor. Systolic blood pressure and heart rate increased significantly during exercise in all three study groups. The increase in plasma NE and DHPG concentrations during exercise-induced sympathetic nervous sy stem stimulation in patients with Pheo is similar to that in normal su bjects and may indicate that the sympathetic nervous system plays an i mportant role in the pathogenesis of hypertension and hypertensive cri ses in patients with Pheo.