Introduction

Postural Orthostatic Tachycardia Syndrome (POTS) is a diverse disorder of the autonomic nervous system. It is defined by a heart rate increase exceeding 30 bpm in infants and children, and over 40 bpm in adolescents and adults. This typically occurs within the initial 10 minutes of standing, accompanied by symptoms including dizziness, fatigue, and palpitations. There are three main types of POTS:  

• Neuropathic POTS
• Hyperadrenergic POTS
• Hypovolemic POTS

Neuropathic POTS

The most common kind of autonomic neuropathy, accounting for 70% to 80% of cases, is neuropathic POTS. Autonomic neuropathy, or neuropathic POTS, is a disorder in which autonomic nerve fibres are damaged. The body's involuntary processes, including blood pressure and heart rate, are controlled by the autonomic nervous system.¹

Pathophysiology

Partial autonomic neuropathy (AN), which especially affects sympathetic vasoconstriction in the lower limbs, is the cause of neuropathic POTS. When standing, this causes blood to pool in the legs, which lowers cardiac output and venous return. This causes the heart rate to instinctively rise in order to maintain blood pressure.

Causes and symptoms

Neuropathic POTS has an unknown cause. However, possible causes could be genetic defects, viral infections, or autoimmune diseases.

Symptoms include:

• Tachycardia.
• Lightheadedness or dizziness
• Periods of fainting or near fainting
• Headache
• Fatigue

Diagnostic criteria

There are different criteria that would lead to a neuropathic POTS diagnosis:

• Thermoregulatory Sweat Test: There is evidence of diminished sweating in the lower limbs in individuals with neuropathic POTS
• Norepinephrine Spillover Studies: individuals with neuropathic POTS show decreased release of norepinephrine in the lower limbs⁴ 

Treatment and management

Treatment for neuropathic POTS usually consists of a combination of pharmaceutical and non-pharmaceutical interventions. Medications may include:^{1, 2}

• Beta blockers to regulate heart rate
• Fludrocortisone to increase blood volume
• Midodrine to increase blood pressure
• SSRI medication to regulate the function of the autonomic nervous system

Additionally, there are certain lifestyle changes that can be implemented to help manage this condition, which include:

• Increasing salt and water intake to increase blood volume
• Wearing compression stockings to enhance the circulation of the blood
• Engaging in regular exercise to improve cardiovascular fitness
• Engaging in relaxation activities

Hyperadrenergic POTS

Pathophysiology

Hyperadrenergic POTS is a less common type, accounting for nearly 10–20% of patients. It is characterised by excessive activity of the sympathetic nervous system (SNS) and the consequent high levels of plasma norepinephrine upon standing. This hyperadrenergic state results in increased heart rate, blood pressure lability, and other adrenergic symptoms.

Causes and symptoms

Even though the exact cause of this condition is largely unknown, it is thought to be related to genetic mutations. Symptoms ¹ may include:

• Rapid heart rate (tachycardia) upon standing
• Hypertension (high blood pressure)
• Anxiety or panic attacks
• Tremors or shaking
• Sweating or flushing

Diagnosis criteria

There are different criteria that would lead to a hyperadrenergic POTS diagnosis. One includes measuring the level of plasma norepinephrine. A level above 600 pg/mL is considered good. Blood pressure monitoring can be utilised, and in individuals with hyperadrenergic POTS, blood pressure fluctuations can be observed. With exclusion of other causes, pheochromocytoma and similar presentations should be ruled out.

Treatment and management

Pharmacological and non-pharmacological methods can be used to treat and manage hyperadrenergic POTS. 

Medications include:³

• Antihistamines or antidepressants
• Beta blockers to regulate heart rate
• Alpha blockers to reduce blood pressure
• Clonidine to reduce SNS activity
• SSRIs to regulate ANS function

Lifestyle modifications may include:

• Regular physical activity: This would increase cardiovascular fitness 
• Stress-reducing activities (yoga, meditation) 
• Reducing or avoiding stimulants (caffeine, nicotine)
• Good sleep hygiene and a healthy diet

Hypovolemic POTS

There is a rare type, Hypovolemic POTS, which comprises about 5-10% of cases. It is due to a reduction in blood volume that can result in symptoms such as lightheadedness, fatigue, and tachycardia.

Pathophysiology

In hypovolemic POTS, blood volume is reduced. This leads to an insufficient venous return and cardiac output when standing. This volume deficit is commonly associated with dysfunction of the renin-angiotensin-aldosterone system, affecting fluid and electrolyte balance.

Causes and symptoms

While the exact cause for hypovolemic POTS is often undetermined, it's thought to be related to dehydration, blood loss or certain medications and post-infections. Symptoms may include:¹

• Increased heart rate (tachycardia) upon standing
• Dizziness or lightheadedness
• Fatigue
• Headaches
• Nausea or vomiting

Diagnosis criteria

There are different criteria that would lead to a hypovolemic POTS diagnosis. Reduced plasma blood volumes can be observed during a blood volume assessment. Renin and aldosterone measurements reveal low concentrations because they don’t withstand orthostatic stress. If the low blood volume is caused by gastrointestinal issues such as diarrhoea, vomiting, or fluid leaking into other parts of the body where it doesn’t belong, these issues should be looked at as possible causes of hypovolemic POTS.

Treatment and management

The treatment for hypovolemic POTS typically involves increasing blood volume.² Methods include:

• Increasing salt and water intake
• Wearing compression stockings to improve blood flow
• Engaging in regular physical activity is crucial for enhancing cardiovascular fitness
• If possible, avoid medications that reduce blood volume, such as diuretics

Conclusion

In conclusion, POTS can be very difficult to understand as a complex multisystem syndrome that affects many people worldwide. Knowing the difference between neuropathic, hyperadrenergic, and hypovolemic POTS is important for developing effective treatment and management strategies. By working closely with a healthcare provider and making lifestyle changes, a patient with POTS can control their symptoms, reduce their medications, and improve their quality of life.

Frequently asked questions

What is POTS?

POTS is a condition characterised by a rapid increase in heart rate and other symptoms that occur upon standing.

What are the different types of POTS?

There are three main types of POTS: neuropathic, hyperadrenergic, and hypovolemic.  Neuropathic POTS is the most common type of POTS and causes 70-80% of the cases. Damage to the nervous system is what causes this type of POTS. Hyperadrenergic POTS makes up 10-20% of the cases. Overactivity of the sympathetic system is what causes this type. Hypovolemic POTS is the least common of them all, only accounting for about 5-10% of the cases. Decreased blood volume is the main cause of this POTS.

What are the symptoms of POTS?

Symptoms of POTS may include rapid heart rate, dizziness, fatigue, headaches, and nausea.

How is POTS diagnosed?

POTS is typically diagnosed through a combination of medical history, physical examination, and diagnostic tests, such as heart rate and blood pressure monitoring.

What are the treatment options for POTS?

Treatment options for POTS may include medications, lifestyle modifications, and alternative therapies, such as acupuncture and cognitive behavioural therapy.