TABLE 1.

Pathophysiologic Mechanisms of Orthostatic Intolerance in POTS

Mechanism (POTS subtype)	Markers	Examples
Impaired sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS)	Impaired distal sweating Blunted late phase II in the VMLow supine blood pressureReduced NE spillover in leg veinsReduced cardiac MIBG uptakeHigh leg blood flow	Restricted postviral or autoimmune neuropathies
Excessive cardiac sympathoexcitatory responses (hyperadrenergic POTS)	Standing plasma NE ≥600 pg/mL Fluctuating blood pressure or hypertension during HUT	AnxietyPheochromocytomaMast cell activation disordersVGKC autoimmunity?
Volume dysregulation	Elevated plasma angiotensin IIImpairment of RAA systemImpaired renal control of fluid secretion	Conditions associated with hypovolemia
Physical deconditioning	V̇o2max <85% on exercise testingReduced left ventricular mass	Prolonged bed restChronic fatigue, pain

HUT = head-up tilt; MIBG = meta-iodobenzylguanidine; NE = norepinephrine; POTS = postural tachycardia syndrome; RAA = renin-angiotensin-aldosterone; VGKC = voltage-gated potassium channel; VM = Valsalva maneuver; V̇o_2max = maximum oxygen consumption.