What Causes Secondary POTS? Triggers & Conditions Explained

When you are diagnosed with Postural Orthostatic Tachycardia Syndrome (POTS), your doctor will likely try to determine whether your condition is “primary” or “secondary.” While primary POTS happens on its own without a clear underlying medical cause, secondary POTS is triggered by another identifiable disease or condition that damages the autonomic nervous system ^[1]. In secondary POTS, your body’s ability to maintain proper blood flow and vascular tone is impaired by a specific underlying issue ^[1]. This often involves small fiber neuropathy, which is damage to the small nerve endings that control involuntary bodily functions like heart rate and blood pressure ^[2].

The most common causes of secondary POTS include viral infections, immune conditions, metabolic disorders, and certain protein abnormalities ^[3]. Identifying the cause is an important part of your care journey, as addressing the root issue can significantly improve your symptoms.

Viral Infections

Many people with POTS can trace the onset of their symptoms back to a severe viral illness. Viruses can trigger a prolonged immune response or lead to post-viral autonomic dysregulation ^[4].

• COVID-19: A notable number of people who develop “long COVID” or post-acute sequelae of SARS-CoV-2 (PASC) meet the criteria for a POTS diagnosis ^[5][6].
• Epstein-Barr Virus (EBV): The virus responsible for infectious mononucleosis (mono) has also been documented as a trigger for POTS ^[4].

Immune and Autoimmune Conditions

In autoimmune diseases, your immune system mistakenly attacks your own body. If it attacks the nerves that control your heart rate and blood vessels, secondary POTS can develop ^[7].

• Sjögren’s Syndrome: This autoimmune condition (which classically causes severe dry eyes and mouth) is a well-documented cause of secondary POTS ^[8]. In some patients, the presence of specific autoantibodies (like anti-gAChR) indicates that the immune system is targeting the autonomic nervous system ^[9].
• Mast Cell Activation Syndrome (MCAS): MCAS is an immunological disorder where immune cells release too many chemical mediators (like histamine). While not strictly an autoimmune disease, it frequently coexists with POTS and can drive severe autonomic symptoms ^[10][7].
• Note on Joint Hypermobility: While typically considered a distinct comorbidity rather than a secondary cause, conditions like Ehlers-Danlos Syndrome (EDS) and joint hypermobility spectrum disorders are very frequently seen alongside POTS and MCAS ^[11][3].

Metabolic and Infiltrative Diseases

Conditions that cause widespread nerve damage or abnormal protein buildup in tissues can also disrupt the autonomic nervous system.

• Diabetic Neuropathy: Prolonged high blood sugar from diabetes can damage the sympathetic nerves responsible for controlling blood vessels. While more commonly associated with orthostatic hypotension, diabetes is a known cause of secondary autonomic dysfunction and sometimes POTS ^[12].
• Amyloidosis: This rare disease occurs when an abnormal protein called amyloid builds up in your organs and tissues. Certain hereditary forms (like ATTRv amyloidosis) can cause early cardiovascular autonomic dysfunction ^[13][14].

Paraneoplastic Syndromes

Rarely, secondary POTS can be triggered by a paraneoplastic syndrome ^[15]. This is an immune response triggered by a cancerous tumor (such as small cell lung cancer or bladder cancer) ^[16][17]. Instead of the tumor directly pressing on nerves, the immune system creates antibodies to fight the cancer, which mistakenly attack the autonomic nervous system ^[15]. Because of this, autonomic symptoms can sometimes be the very first sign of an undiagnosed cancer ^[17].

Please do not panic if you read this. Paraneoplastic syndromes are rare. If your doctor suspects this could be a factor, they will routinely screen for specific antibodies and conduct imaging to ensure your safety and provide peace of mind ^[15][18].

Managing Symptoms vs. Treating the Cause

If you have secondary POTS, standard symptom management (like increased salt, hydration, compression garments, or medications like ivabradine) remains a critical part of your care to improve your daily quality of life ^[19]. You do not have to wait to find a root cause before you start treating your POTS symptoms.

However, finding and addressing the underlying condition is a crucial goal for long-term improvement ^[20]. For treatable triggers—like an autoimmune disease or a paraneoplastic syndrome—therapies that calm the immune system or address a tumor can lead to significant improvements, and sometimes a complete regression of autonomic symptoms ^[15][21]. For post-viral triggers, where the virus is already gone, the focus shifts to supporting your body’s recovery and managing the immune aftermath.

What an Autonomic Evaluation Looks Like

To uncover secondary causes, work closely with a specialist for a comprehensive autonomic evaluation ^[20]. This process can take time, so be patient with yourself and your care team. An evaluation may include:

• Detailed Medical History: Discussing when symptoms started and your family history ^[22].
• Tilt Table Testing: To monitor how your heart rate and blood pressure respond to changes in posture ^[23].
• Autonomic Testing (like QSART): To measure how well your small nerve fibers control sweating.
• Blood Panels: To check for autoimmune markers, metabolic issues, or specific autoantibodies (like gAChR) ^[20][9].
• Neuropathy Biopsies: A small skin biopsy to check for small fiber nerve damage ^[2].