So as of right now, what do we believe may trigger or cause POTS?

Researchers such as Fedorowski (2019) have found that there are a number of possible triggers, many of which are considered to be immunological stressors. These can include viral infections such as COVID-19, Epstein-Barr, and Influenza, and bacterial infections such as Borrelia burgdorferi, just to name a few, underlying illnesses (such as Ehlers-Danlos Syndrome or Multiple Sclerosis), traumatic head injuries, pregnancy, puberty, vaccinations, other forms of trauma, and surgeries (Blitshteyn et al., 2021; Thieben et al., 2007; Noyes et al., 2014).

More research is also pointing to mast cell activation syndrome (MCAS) as a potential trigger (Kohno et al., 2021). MCAS is viewed as a co-occurring condition for a number of individuals with POTS, so understanding the underlying link and what the underlying mechanism may be, could provide us with many helpful answers and additional treatment options (Kohno et al., 2021). Researchers found that the presence of an elevated prostaglandin (prostaglandin D2 and/or F2 alpha), particularly when in combination with an increase in histamine or, less often, tryptase, may be suggestive of MCAS, also known as MCA disorder (Kohno et al., 2021).

Individuals with POTS are often misdiagnosed with anxiety or other psychological disorders. Although the illness itself can be frightening and lead some to understandably feel anxious or appear anxious when experiencing their debilitating symptoms, they do not have “excess cognitive anxiety” (Raj et al., 2009). These researchers found that those with diagnoses of POTS were not more likely to have psychiatric diagnoses such as panic disorder, or anxiety, as compared to the general population, despite appearing anxious or struggling with attention deficit (Raj et al., 2009).

There is also growing evidence that some forms of POTS may be autoimmune in nature. Researchers have found that some individuals with POTS have antinuclear antibodies and also have elevated levels of ganglionic, adrenergic, and muscarinic acetylcholine receptor antibodies. Their observations provided evidence that those with POTS had one or more elevated G-protein coupled adrenergic autoantibodies in most cases (Gunning III et al., 2019). More recent research found that of those diagnosed with primary POTS (POTS not caused by or exacerbated by underlying conditions), 100% of them had A1 adrenergic receptor autoantibodies, and 55.9% had M4 muscarinic acetylcholine receptor autoantibodies (Gunning III et al., 2021).

These findings are quite significant because they may lead us closer to developing a blood test that could test for the presence of antibodies. This would allow providers to more easily, quickly, and accurately diagnose individuals with POTS (Gunning III et al., 2019). It will still take time and research to help us understand the differences between the different types of POTS and how these findings can also help those with various presentations, which you can read about in the Types Of POTS section.

Sources:

Blitshteyn, S., & Whitelaw, S. (2021). Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: A case series of 20 patients. Immunologic Research, 69(2), 205–211. https://doi.org/10.1007/s12026-021-09185-5 

Fedorowski, A. (2019). Postural orthostatic tachycardia syndrome: Clinical presentation, Aetiology and management. Journal of Internal Medicine, 285(4), 352–366. https://doi.org/10.1111/joim.12852

Gunning, W. T., Kvale, H., Kramer, P. M., Karabin, B. L., & Grubb, B. P. (2019). Postural orthostatic tachycardia syndrome is associated with elevated g‐protein coupled receptor autoantibodies. Journal of the American Heart Association, 8(18). https://doi.org/10.1161/jaha.119.013602

Gunning, W. T., Stepkowski, S. M., Kramer, P. M., Karabin, B. L., & Grubb, B. P. (2021). Inflammatory biomarkers in postural orthostatic tachycardia syndrome with elevated G-protein-coupled receptor autoantibodies. Journal of Clinical Medicine, 10(4), 623. https://doi.org/10.3390/jcm10040623

Kohno, R., Cannom, D. S., Olshansky, B., Xi, S. C., Krishnappa, D., Adkisson, W. O., Norby, F. L., Fedorowski, A., & Benditt, D. G. (2021). Mast cell activation disorder and postural orthostatic tachycardia syndrome: A clinical association. Journal of the American Heart Association, 10(17). https://doi.org/10.1161/jaha.121.021002

Noyes, A. M., & Kluger, J. (2014). A tale of two syndromes: Lyme disease preceding postural orthostatic tachycardia syndrome. Annals of Noninvasive Electrocardiology, 20(1), 82–86. https://doi.org/10.1111/anec.12158

Raj, V., Haman, K. L., Raj, S. R., Byrne, D., Blakely, R. D., Biaggioni, I., Robertson, D., & Shelton, R. C. (2009). Psychiatric profile and attention deficits in postural tachycardia syndrome. Journal of Neurology, Neurosurgery & Psychiatry, 80(3), 339–344. https://doi.org/10.1136/jnnp.2008.144360

Thieben MJ, Sandroni P, Sletten DM, et al. (2007). Postural orthostatic tachycardia syndrome: the Mayo Clinic experience. Mayo Clin Proc.;82:308–313. doi: 10.4065/82.3.308.