Unfortunately and frustratingly there is no one clear cause of POTS Syndrome. In the following section we will discuss causes of POTS. Older people with POTS will have it due to another disorder such as diabetes or other condition. It is known as secondary POTS in that case, because it is secondary to something else. Younger adults and children will most likely have a primary form of POTS.
Primary Causes of POTS
Mast Cell Disorders
Mast cells are cells of the immune system. When someone with an allergy touches something they are allergic to, there is redness and itching of the area touched. This is partly due to mast cells coming to the area and releasing tiny chemical containing granules in to the area. Flushing episodes with light-headedness, nausea, stomach cramping and headache are well described in POTS. In some cases of POTS with these symptoms, treatment directed towards preventing triggering of mast cells, or preventing the actions of the released chemicals may be helpful (Shibao et al)
The symptoms of orthostasis and tachycardia in POTS have been attributed to pooling of blood in the legs. This means that blood that is meant to get back to the heart and the upper body, stays in the legs and leads to the symptoms of dizziness. The heart rate increases in order to try and pump more blood to make up for this. In normal subjects, tightening of the vessels in an attempt to pump blood back to the heart prevents the pooling of blood in the lower extremities. This tightening of the vessels is caused by signals from nerves on the vessels. In POTS there may be loss of the nerve supply to the vessels preventing them from functioning normally (Jacob et al).
Also known as nor-adrenaline, nor-epinephrine is an excitatory transmitter typically produced in response to stress. Interestingly, and as discussed many times in this article, even standing up can be a stress, but normally our bodies can handle that by activating reflex reactions. In POTS, the normal reflexes that make standing tolerable may be dysfunctional.
In the less common hyperadrenergic POTS there is excess levels of nor-epinephrine seen on standing. Hyperadrenergic POTS treatment is targeted towards preventing release of these transmitters or prevention of their action.
There is also a rare form of POTS syndrome attributed to a genetic abnormality causing failure of clearance of the nerve-transmitters meaning higher levels of these, possibly leading to the symptoms of the dizziness and increased heart rate on standing (Shannon et al).
Nitric oxide is a substance in the blood that helps to regulate the function of the cardiovascular system. Some studies have suggested that in POTS, the interaction of nitric oxide with the autonomic nervous system may be dysfunctional and related to symptoms (Gamboa et al).
POTS shares a lot in common with chronic fatigue disorders, and may lead to high levels of inactivity with associated deconditioning. Also, physical deconditioning may lead to a smaller heart size, which may lead to decreased cardiac output. It’s difficult to know whether deconditioning leads to POTS, or POTS leads to deconditioning, however it’s likely a combination of both. Regardless, there is association between POTS, deconditioning and decreased heart size that underscores the importance of maintaining physical activity in POTS. (Fu et al)
Around 1/3rd of POTS patients report a viral kind of infection before the onset of P.O.T.S Syndrome symptoms (Thieben et al)(Kimpinski et al). The exact way in which a virus leads to this is not known at this time. It may be by directly damaging the nervous system or by stimulating the production of antibodies that damage the nervous system.
Secondary Causes of POTS
The adrenal gland is a gland that sits on the kidney and produces the stress hormone cortisol and other important hormones that help to maintain adequate salt and water in the body. This is important in maintaining blood pressure. In adrenal insufficiency the lack of these hormones can lead to orthostatic symptoms and a low blood pressure. In addition there is weakness and fatigue and many of the other symptoms associated with POTS.
Anemia can often mimic the symptoms seen in POTS. Folic acid and vitamin B12 deficiencies that lead to anemia may also be considered. Typically simple blood tests can rule these out. There are some POTS patients however that may have a low number of blood cells, which leads to anemia, despite normal standard testing (Raj et al).
In some case of POTS, there has been underlying autoimmune disorders such as lupus suspected of causing the symptoms. There have also been reports of POTS associated with the viral illness triggered Guillain-Barre syndrome, a syndrome that attacks the nerves supplying the muscles causing weakness. In addition there are a number of rarer autoimmune conditions where antibodies attack the autonomic nervous system (POTS is attributed to autonomic dysfunction) and cause POTS syndrome.
Ehlers-Danlos syndrome is an inherited disorder that affects connective tissues. These are the tissues found in the skin, the blood vessels, and joints and allow those tissues to have strength and elasticity. So as you can imagine, people with Ehlers-Danlos syndrome have flexible joints and fragile skin. Ehlers-Danlos syndrome is more common amongst POTS patients than the general population (Wallman et al). It has been suggested that this is due to weakness in the blood vessels leading to pooling of blood in the lower extremities, a mechanism that has been well associated with the POTS syndrome (Rowe et al). It’s therefore reasonable to check for features of Ehlers-Danlos in those presenting with POTS.
Gastric Bypass Surgery
Gastric bypass surgery is a popular treatment for morbid obesity. As more and more of these procedures have been performed it has been recognized that some patients may develop orthostatic intolerance following the surgery (Billakanty et al).
Lyme disease is an illness develops after a particular tick bite. It affects many organ systems including the nerves, the heart and the muscles. Usually it responds to antibiotics, however some patients develop what is known as post Lyme disease syndrome of fatigue, pain and mental clouding. Some patients with Lyme disease and the post Lyme disease syndrome are noted to suffer from POTS syndrome. Recognizing POTS syndrome in these patients is important because the appropriate treatment of POTS syndrome may result in improvement in symptoms and quality of life (Kanjwal et al).
Spinal cord injury is well known to be associated with autonomic dysfunction (Karlsson). The complications of acute spinal injury may even be life threatening with problems such as uncontrolled high blood pressure. The whole of the autonomic system function may be affected with complications including bladder and bowel control, renal and sexual function. Some of the effects may be worse in the early phase after injury and a new balance achieved a few months after the injury. In addition, structural brain disorders such as the Chiari malformation may be associated with POTS (Prilipko et al). In that malformation the brain is displaced downwards leading to compression.
The hyperadrenergic form of POTS is partly caused by elevated levels of the excitatory nerve transmitter nor-epinephrine. The tumor called pheochromocytoma produces excess levels of this transmitter and can be associated with flushing, elevated blood pressure, palpitations and tachycardia. These symptoms are similar to some of the changes seen in hyperadrenergic POTS. There are other rare tumors that may secrete factors that can lead to autonomic dysfunction such as neuroblastoma, and paraganglioma.
As noted in the section above, abnormality in nor-epinephrine, the stimulatory transmitter has been implicated in POTS. Vitamin B12 is known to be critical to the functioning of the nervous system including the normal chemical pathways involving nor-epinephrine, and nerve tissue integrity. Vitamin B12 deficiency in patients with POTS may lead to nervous system dysfunction (Oner et al).