The rates of norepinephrine release into plasma and removal from plasma were studied in patients with idiopathic peripheral autonomic insufficiency (sympathetic neuronal dysfunction), as it was thought that plasma norepinephrine concentration alone inadequately quantifies the degree of sympathetic nervous underactivity in this disorder. In four patients with autonomic insufficiency, clearance of norepinephrine from the circulation was slowed, 1.69 +/- 0.44 liters/min, compared with 2.80 +/- 0.73 liters/min in 10 normal subjects (P less than 0.05). As a consequence, despite a 60% lower norepinephrine apparent secretion rate, 0.19 +/- 0.12 microgram/m2 per min vs. 0.54 +/- 0.20 microgram/m2 per min, the plasma norepinephrine concentration was near normal. The plasma concentration of neurotransmitter does not provide a valid index of sympathetic nervous tone in this disorder in which removal of norepinephrine from the circulation is slowed.

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