Postural Orthostatic Tachycardia Syndrome - Causes

Causes

The causes of POTS are not fully known. Most patients develop symptoms in their teenage years during a period of rapid growth and see gradual improvement into their mid-twenties. Others develop POTS after a viral or bacterial infection such as mononucleosis or pneumonia. Some patients develop symptoms after experiencing some sort of trauma such as a car accident or injury. Women can also develop POTS during or after pregnancy. These patients generally have a poorer prognosis.

In one large test, 12.5% of 152 patients with POTS reported a family history of orthostatic intolerance, suggesting that there is a genetic inheritance associated with POTS.

So far, no one has provided an explanation for POTS that is applicable to all sufferers. However, there are many theories:

• Alpha-receptor dysfunction may be occurring in some POTS patients. Alpha-1 receptors cause peripheral vasoconstriction when stimulated. Alpha-1 receptor supersensitivity may be causing dysautonomia in some patients.

• An autoimmune process has been suggested as a causal mechanism in many POTS patients, supported by the finding of autoantibodies against ganglionic alpha 3 acetylcholine receptors in a percentage of POTS patients. Anecdotally it has been suggested that POTS patients exhibit higher comorbid autoimmune diseases than the general population and frequently report a family history of autoimmunity or migraine.

• POTS patients frequently exhibit low blood volume or hypovolumia yet some patients appear to have an abnormal renin-aldosterone response to this volume deficit. This may account for the dramatic improvement some patients experience after intravenous saline.

• Beta-receptor supersensitivity may occur with hyperadrenergic states in some people with POTS.

• Hyperdopaminergic states may be the underlying problem for some people with orthostatic intolerance. Some patients have been found to have a significant increase in upright dopamine levels. Free plasma norepinephrine also tends to be higher in these patients. Increased peripheral dopamine is associated with increased extraction of salt from plasma by the kidneys.

• Reduced venous return is one of the main mechanisms that cause POTS symptoms. Venous return can be reduced due to conditions such as hypovolemia (low plasma volume/low blood volume), venous pooling, and denervation. A hyperadrenergic state may result as the body attempts to compensate for these abnormalities.

Anything that can damage the autonomic nervous system can potentially cause POTS. There are hundreds of things that can cause autonomic nerve damage, for example:

• physical traumas to autonomic nerves (car accidents, falls, head/spinal injuries during sports)
• toxic drug and chemical exposures (heavy metal poisoning, organophosphate pesticide poisoning, some chemotherapy drugs, thallium, pyridoxine, etc.)
• vitamin deficiencies (B12 is the most common vitamin deficiency associated with autonomic neuropathy)
• infectious or acute diseases, such as HIV, Diphtheria, Chagas Disease, Lyme Disease, and Guillain Barre Syndrome
• chronic diseases, such as CIDP, Diabetes, Multiple Sclerosis, Sjogren's Syndrome, Lupus, Celiac Disease and other autoimmune diseases.
• inherited or genetic diseases (Familial Dysautonomia, Hereditary Sensory Autonomic Neuropathy)

Additional causes of Autonomic Neuropathy are described on Medscape.

Expression of Norepinephrine transporter (NET) protein appears to be reduced in some POTS patients. Cardiac neurotransmission imaging of norepinephrine reuptake measured utilising MIBG has also been found to be abnormal in some POTS patients, suggesting cardiac denervation or NET deficiency.

Levels or activation of endothelial vasodilating molecules such as nitric oxide or hydrogen sulfide may be increased in some POTS patients.

Sympathetic Overactivity is observed in many POTS patients. The sympathetic overactivity can be secondary to a number of factors, some of which may be peripheral denervation, venous pooling, or end-organ dysfunction. Sympathetic underactivity can also occur in some forms of orthostatic intolerance, such as pure autonomic failure.

Recent studies have described a subset of POTS patients that appear to have elevated angiotensin II levels coupled with paradoxically reduced absolute blood volume, signs of increased sympathetic activity and reduced peripheral blood flow. This subset of POTS patients appear to have abnormal catabolism of Angiotensin II that may contribute to reduced blood volume and orthostatic intolerance.

An epigenetic mechanism (hypermethylation of CpG islands in the NET gene promoter region) that results in reduced expression of the noradrenaline (norepinephrine) transporter and consequently a phenotype of impaired neuronal reuptake of norepinephrine has been implicated in both postural orthostatic tachycardia syndrome and panic disorder.