Background: Neurogenic orthostatic hypotension (NOH) usually results from deficient release of the sympathetic neurotransmitter norepinephrine (NE) when the patient stands up. In pure autonomic failure (PAF) and PD with NOH, sympathetic denervation can explain this deficiency, whereas in multiple-system atrophy (MSA), deficient baroreflex regulation of sympathetic traffic to intact terminals probably causes the NOH. From the concept of a unitary sympathoadrenomedullary system, one might predict parallel sympathoneural and adrenomedullary abnormalities in NOH.

Objective: To test the concept of parallel sympathoneural and adrenomedullary abnormalities in NOH by simultaneous measurements of plasma levels of catechols and metanephrines.

Methods: Antecubital venous blood drawn via an indwelling cannula with the subject supine was assayed for catecholamines (NE, epinephrine [EPI]), dihydroxyphenylglycol (DHPG), and metanephrines (normetanephrine [NMN] and metanephrine [MN]) in patients with PAF, PD + NOH, or MSA + NOH. Control subjects had PD lacking NOH or were normal volunteers at least 35 years old. Cardiac sympathetic innervation was assessed by 6-[¹⁸F]fluorodopamine PET scanning.

Results: The three NOH groups differed clearly in patterns of plasma catechols and metanephrines. The PAF group had low NE, DHPG, NMN, EPI, and MN levels, the group with MSA + NOH had generally normal levels, and the PD + NOH group low NMN levels and low DHPG levels for given NE levels but normal mean NE, EPI, and MN levels. All patients with PAF or PD + NOH had markedly decreased 6-[¹⁸F]fluorodopamine-derived radioactivity throughout the left ventricular myocardium; all patients with MSA + NOH had normal radioactivity.

Conclusions: PAF involves generalized loss of sympathoadrenomedullary cells, MSA + NOH intact sympathoadrenomedullary cells, and PD + NOH intact adrenomedullary cells but organ-selective sympathetic denervation, especially in the heart.