What causes hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS)?

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Last updated: March 17, 2025 • View editorial policy

From the Guidelines

Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS) is primarily caused by a hyperadrenergic state, which is one of the proposed pathophysiologies of POTS, along with deconditioning, immune-mediated processes, and excessive venous pooling. The pathophysiology of POTS is debated and likely heterogeneous, as noted in the 2018 ESC guidelines for the diagnosis and management of syncope 1.

Key Characteristics of Hyperadrenergic POTS

  • Elevated levels of norepinephrine and other catecholamines when standing
  • Significant increases in heart rate upon standing, often >30 b.p.m. or >120 b.p.m. within 10 min of standing
  • Associated symptoms include light-headedness, palpitations, tremor, generalized weakness, blurred vision, and fatigue
  • Frequently associated with deconditioning, recent infections, chronic fatigue syndrome, joint hypermobility syndrome, and non-specific symptoms such as headache and chest pain

Management of Hyperadrenergic POTS

  • Beta-blockers and central sympatholytics are often used to reduce sympathetic outflow, although specific dosing and medication selection may vary depending on individual patient needs
  • Lifestyle modifications, including increased fluid intake, increased salt consumption, compression garments, and gradual exercise conditioning, are also essential for managing symptoms

The hyperadrenergic state in POTS is a key factor in determining the most effective treatment approach, as noted in the guidelines 1. By understanding the pathophysiology of hyperadrenergic POTS, healthcare providers can develop targeted treatment plans to improve patient outcomes and quality of life.

From the Research

Causes of Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS)

  • Hyperadrenergic POTS is caused by an excessive sympathetic drive, which can be due to various factors, including impaired sympathetically mediated vasoconstriction, volume dysregulation, and deconditioning 2
  • The pathophysiology of POTS is heterogeneous and includes several mechanisms, such as limited autonomic neuropathy, hyperadrenergic state, hypovolemia, venous pooling, and deconditioning, which are not mutually exclusive 3
  • Anxiety and somatic hypervigilance play significant roles in POTS, and patients with POTS often have comorbid conditions, such as attention deficit hyperactivity disorder, depression, or fibromyalgia, which can contribute to the development of a hyperadrenergic state 3, 4
  • Norepinephrine reuptake inhibition, which can increase sympathetic nervous system tone, may also contribute to the development of hyperadrenergic POTS 4
  • The etiology of POTS is largely unknown, but the three major hypotheses about the pathophysiology of POTS are autoimmunity, abnormally increased sympathetic activity, and sympathetic denervation leading to central hypovolemia and reflex tachycardia 5

Key Factors Contributing to Hyperadrenergic POTS

  • Excessive sympathetic drive
  • Impaired sympathetically mediated vasoconstriction
  • Volume dysregulation
  • Deconditioning
  • Anxiety and somatic hypervigilance
  • Comorbid conditions, such as attention deficit hyperactivity disorder, depression, or fibromyalgia
  • Norepinephrine reuptake inhibition

Pathophysiologic Mechanisms

  • Limited autonomic neuropathy
  • Hyperadrenergic state
  • Hypovolemia
  • Venous pooling
  • Deconditioning
  • Autoimmunity
  • Sympathetic denervation leading to central hypovolemia and reflex tachycardia 3, 2, 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.