Background-Patients with postural tachycardia syndrome (POTS) experience considerable disability, but in most, the pathophysiology remains obscure. Plasma volume disturbances have been implicated in some patients. We prospectively tested the hypothesis that patients with POTS are hypovolemic compared with healthy controls and explored the role of plasma renin activity and aldosterone in the regulation of plasma volume. Methods and Results-Patients with POTS (nϭ15) and healthy controls (nϭ14) underwent investigation. Heart rate (HR), blood pressure (BP), plasma renin activity, and aldosterone were measured with patients both supine and upright. Blood volumes were measured with 131 I-labeled albumin and hematocrit. Patients with POTS had a higher orthostatic increase in HR than controls (51Ϯ18 versus 16Ϯ10 bpm, PϽ0.001). Patients with POTS had a greater deficit in plasma volume (334Ϯ187 versus 10Ϯ250 mL, PϽ0.001), red blood cell volume (356Ϯ128 versus 218Ϯ140 mL, Pϭ0.010), and total blood volume (689Ϯ270 versus 228Ϯ353 mL, PϽ0.001) than controls. Despite the lower plasma volume in patients with POTS, there was not a compensatory increase in plasma renin activity (0.79Ϯ0.58 versus 0.79Ϯ0.74 ng · mL Ϫ1 · h
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