How do I differentiate between Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS) and Neuropathic Postural Orthostatic Tachycardia Syndrome (POTS)?

From the Guidelines

To differentiate between Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS) and Neuropathic Postural Orthostatic Tachycardia Syndrome (POTS), a comprehensive diagnostic approach is necessary, including a catecholamine blood test, QSART, or skin biopsy, as well as a thorough clinical evaluation, as outlined in the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1.

Diagnostic Approach

The main distinguishing tests for Hyperadrenergic POTS and Neuropathic POTS include:

• A catecholamine blood test, where elevated norepinephrine levels (typically >600 pg/mL) while standing suggest hyperadrenergic POTS
• QSART (Quantitative Sudomotor Axon Reflex Test) or skin biopsy showing reduced small fiber nerve density for neuropathic POTS

Clinical Symptoms

Clinical symptoms may also help differentiate between the two subtypes:

• Hyperadrenergic POTS often presents with prominent anxiety, tremor, high blood pressure surges, and excessive sweating
• Neuropathic POTS typically features more severe blood pooling in the legs, exercise intolerance, and sometimes gastrointestinal issues

Tilt Table Test

A tilt table test showing a heart rate increase of 30+ beats per minute (40+ for those 12-19 years old) within 10 minutes of standing confirms POTS generally, but additional autonomic testing is needed to determine the specific subtype, as stated in the guidelines 1.

Treatment Approaches

The distinction between Hyperadrenergic POTS and Neuropathic POTS matters because treatment approaches differ:

• Beta-blockers like propranolol work well for hyperadrenergic POTS
• Midodrine or fludrocortisone may be more effective for neuropathic POTS It is essential to consult with a cardiologist or autonomic specialist to perform these diagnostic tests and develop an appropriate treatment plan, as emphasized in the guidelines 1.

From the Research

Differentiating between Hyperadrenergic POTS and Neuropathic POTS

To differentiate between Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS) and Neuropathic POTS, several factors should be considered:

• Definition and Diagnosis: POTS is defined as symptoms of orthostatic intolerance accompanied by a heart rate increase of at least 30 bpm (or a rate that exceeds 120 bpm) that occurs in the first 10 min of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders 2.
• Pathophysiologic Mechanisms: The three major pathophysiologic mechanisms of POTS include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state 3.
• Hyperadrenergic POTS: Characterized by an increase in systolic blood pressure of ≥ 10 mm Hg during the HUTT with concomitant tachycardia or serum catecholamine levels (serum norepinephrine level ≥ 600 pg/mL) upon standing 2.
• Neuropathic POTS: Characterized by partial autonomic neuropathy, which can be evaluated through tests such as estimation of peripheral denervation 4.
• Treatment: The approach to treatment centers on addressing the underlying pathophysiologic mechanism. For hyperadrenergic POTS, beta-blockers and avoidance of norepinephrine reuptake inhibitors are important, while for neuropathic POTS, treatments such as stockings, abdominal binders, and vasoconstrictors are used to enhance venous return 3, 5.
• Norepinephrine Reuptake Inhibition: Norepinephrine reuptake inhibitors can increase sympathetic nervous system tone, worsening symptoms in POTS patients, particularly those with hyperadrenergic POTS 6.