The orthostatic tachycardia syndrome is a disabling disease state described at least since 1940  and is the most common reason for referral for orthostatic intolerance  in adults. It is an emerging form of orthostatic intolerance in children. Patients have day-to-day disability - a feature not shared with most patients with simple faint. With some exception, traditional tests of autonomic function are normal in these patients. Patients are often unable to hold jobs or attend schools. Drs. Schondorf and Low of the Mayo Clinic described a postural tachycardia syndrome (POTS) which is the most frequently used name for the illness. Dr. David Robertson of the Vanderbilt autonomic laboratories, has stated that this is the most common form of chronic orthostatic disability, and is present in almost all patients with day-to-day orthostatic intolerance. Therefore the illness may also be appropriately designated "Chronic Orthostatic Intolerance". Our understanding of its pathophysiology remains incomplete. The central physical finding is upright tachycardia although hypotension and resting tachycardia may also be present. An operational definition of the syndrome  includes symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of more than 30 beats per minute or to a heart rate greater than 120 beats per minute within 10 minutes of head-up tilt (HUT). These numbers may require modification for children. Such a response is depicted in the figure. In the case shown, the patient became immediately symptomatic following the start of HUT and required the table to be put down within a very few minutes. Although this patient was not hypotensive, hypotension may follow or occur with tachycardia. Often hypotension is delayed beyond the onset of the symptoms and the tachycardia, and therefore only manifests during the artificially sustained orthostasis enforced during HUT. Onset of symptoms often follows an infectious disease and may be related to inflammatory mediators. We reported the first pediatric cases of POTS. Our data showed that POTS physiology underlies orthostatic intolerance in the large majority of adolescents with the chronic fatigue syndrome (CFS). POTS is common, affecting an undisclosed number of patients mostly in the age range of 12 to 50 years, mostly female (approximately 80%). There is an as yet undetermined but increasing apparent prevalence in children and adolescents.

Patients with the syndrome display an unusual amount of pooling in the lower extremities often associated with acrocyanosis. It is likely that there are many physiologic mechanisms for POTS. The literature contains a number of potential explanations for abnormal venous pooling and fluid collection in POTS including impaired innervation of the veins or in their response to sympathetic stimulation. One such explanation favors an autonomic neuropathy that predominantly affects the lower extremities. "₁-adrenergic denervation hypersensitivity results. A second explanation invokes decreased $₁- receptor sensitivity; a third, "₁-receptor supersensitivity; a fourth altered venoconstriction, while a fifth  suggests increased capillary filtration as an explanation. However, "₁-adrenergic control of venous filling in response to baroreflex stimulation during orthostasis is important only in splanchnic circulation in humans while involvement of skeletal muscle $₁-receptors remain controversial. Recent data from Vanderbilt indicate a key role for a deficit in norepinephrine release especially from the lower extremities. This agrees nicely with separate data from our lab showing failure of peripheral vasoconstriction in many POTS  patients particularly affecting the lower limbs. Vasoconstrictor failure appears to be heterogeneous in POTS involving skeletal muscle baroreflex sensitive vasculature in some patients while in others "₂ adrenergic baroreflex insensitive local cutaneous mechanisms may predominate which may explain why "₁  adrenergic agonists are ineffective treatments in many cases. "-adrenergic effects may also alter venous filling, but only indirectly through arterial vasoactivity  and this mechanism may be most important during exogenous beta-agonist administration (isoproterenol) or during endogenous epinephrine release later during HUT. Recent data suggest that active venoconstriction is not important to the orthostatic response. Finally, venous capacitance properties in POTS could be abnormal because of altered vascular structure, altered muscle tone or both. Again recent data concerning peripheral venous capacitance properties have, on average, offered little support for this conjecture. A link with antecedent inflammatory disease is the chronic elaboration of cytokines with potent vasoactive consequences such as IL-1, IL-6 and TNF". Such a link seems established in the chronic fatigue syndrome in which POTS and so called "neurally mediated hypotension" (actually POTS) occur with high frequency. Finally, most recently Dr. Robertson and associates have isolated an aberrant gene for the norepinephrine reuptake transporter protein producing alternations between hypertension and hypotension in the same patient (and her twin sister) dependent on norepinephrine stores . This gene seems [for now] confined to a single family. Such results, however, point to the likelihood of different types of vascular abnormalities resulting in a common pathway of postural tachycardia associated with symptoms of orthostatic intolerance.

Our preliminary data  suggest the hypothesis that blood pooling in POTS results from a defect in arterial vasoconstriction during orthostasis causing increased venous filling and enhanced microvascular filtration. Blood is redistributed peripherally and redistribution is enhanced during orthostasis producing increased microvascular filtration and dependent edema. Central hypovolemia causes reflex tachycardia, reduced cerebral blood flow and often hypotension. POTS results in a circulation at high risk for simple fainting by virtue of a depleted thoracic vascular bed. In many ways it resembles hemorrhage or hypovolemia in that tachycardia and malperfusion are first noted which may then proceed to hypotension or loss of consciousness or both.

Effective treatment for chronic orthostatic intolerance is being developed but will depend on specific etiologies as these are discovered. For the moment we continue to use some of the medications outlined in the vasovagal section. Of these florinef and midodrine seem to be most effective with an emerging use of SSRI’s. Beta-blockers and clonidine are rarely tolerated and may point to a very different origin for chronic orthostatic intolerance and POTS from syncope.