Are there multiple subtypes of postural orthostatic tachycardia syndrome (POTS)?

Yes, POTS Has Multiple Recognized Subtypes

POTS is classified into three distinct phenotypes—hypovolemic, neuropathic, and primary hyperadrenergic—each representing different underlying pathophysiological mechanisms that lead to chronic orthostatic intolerance. 1

The Three Primary POTS Subtypes

Hypovolemic POTS

• This subtype is characterized by reduced blood volume and plasma volume dysregulation 2, 3
• Patients often have a history of dehydration, physical deconditioning, or conditions that impair volume regulation 2
• Iron deficiency is a well-recognized contributor to this subtype and should be corrected when ferritin is low 4
• Treatment focuses primarily on volume expansion through increased fluid and salt intake, along with structured exercise reconditioning 2

Neuropathic POTS

• This form results from partial sympathetic denervation, particularly affecting the lower extremities, leading to impaired vasoconstriction during orthostatic stress 2, 5
• The autonomic neuropathy causes inadequate peripheral vascular resistance when standing 6, 3
• Pharmacologic agents that enhance vascular tone, such as pyridostigmine and midodrine, are most effective for this phenotype 2, 6

Primary Hyperadrenergic POTS

• This subtype involves excessive norepinephrine production or impaired reuptake, resulting in sympathetic overactivity 2, 5
• Patients demonstrate elevated sympathetic drive and often have standing norepinephrine levels that are markedly elevated 6, 7
• Beta-blockers are particularly effective for managing the excessive sympathetic activation in this phenotype 2, 6

Clinical Implications of Subtype Recognition

Identifying the predominant POTS phenotype in each patient should guide targeted pharmacologic therapy, though all patients benefit from first-line lifestyle modifications including increased fluid and salt intake, compression garments, and physical reconditioning. 2, 5

Important Overlapping Features

• Many patients exhibit features of more than one subtype simultaneously, making strict categorization challenging in clinical practice 3, 5
• The pathophysiology represents a "final common pathway" where multiple mechanisms converge to produce the characteristic orthostatic tachycardia 6, 3, 7
• Deconditioning may be both a cause and consequence of POTS, often coexisting with other pathophysiological mechanisms 4, 6, 7

Associated Conditions That May Influence Subtype

• POTS frequently coexists with joint hypermobility syndrome and hypermobile Ehlers-Danlos syndrome, where vascular laxity may contribute to the hypovolemic phenotype 1, 8
• Mast cell activation syndrome (MCAS) can overlap with POTS, potentially representing an additional pathophysiological mechanism 1
• Post-viral POTS (including post-COVID-19) can develop as a distinct clinical entity meeting all standard diagnostic criteria 4, 9

Critical Diagnostic Considerations

• The diagnosis of POTS requires a sustained heart rate increase of ≥30 bpm (≥40 bpm in ages 12-19) within 10 minutes of standing, without orthostatic hypotension, plus symptoms lasting ≥3 months 8, 4, 9
• Subtype determination is primarily clinical and based on associated features, response patterns, and when available, specialized autonomic testing 2, 5
• No single test definitively categorizes patients into subtypes; clinical judgment based on the predominant pathophysiology guides treatment selection 3, 5

Common Pitfalls in Subtype Classification

• Attempting to force every patient into a single subtype category when most have overlapping features from multiple phenotypes 3, 5
• Failing to recognize that the subtype may evolve over time or with treatment, requiring reassessment of the therapeutic approach 6, 7
• Overlooking treatable secondary causes (medications, dehydration, anemia, thyroid dysfunction) that may mimic or exacerbate specific POTS phenotypes 8, 4, 6