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Three patients with idiopathic orthostatic (postural) hypotension were infused over a 4-hr period with 104.6 µc of 3-hydroxytyramine-2- 14 C, the immediate precursor in the synthesis of the sympathetic neurohormone, that is, noradrenaline (norepinephrine). Urine was collected during the infusion period and at various intervals thereafter for a total of 5 days. By means of column fractionation, the various metabolic products of hydroxytyramine, including endogenous noradrenaline and its metabolic products, were separated, identified, and their radioactivity measured. From the comparison of the hydroxytyramine metabolic pattern of normal subjects to that of idiopathic orthostatic hypotensive patients, it was apparent that the greatest changes occurred in the formation of noradrenaline and 3-methoxy-4-hydroxymandelic acid (MOMA, VMA). The synthesis of noradrenaline was significantly reduced in the hypotensive patients, and there was also a marked reduction in the formation of MOMA, the principal metabolic product of noradrenaline. The implication of these findings is that the pathogenesis of idiopathic orthostatic hypotension is related to a defect in the neurogenic structures involved in the biosynthesis of noradrenaline. This conclusion is further supported by the fact that one of the subjects (M.Q.) at autopsy showed only degenerative changes in the sympathetic ganglia and neurons.

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