What test identifies hyperadrenergic postural orthostatic tachycardia syndrome (POTS)?

Diagnosing Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS)

The most definitive test to identify hyperadrenergic POTS is measuring serum norepinephrine levels upon standing, with a level ≥600 pg/mL confirming the diagnosis, along with an increase in systolic blood pressure of ≥10 mmHg during standing or head-up tilt testing. 1

Diagnostic Criteria for Hyperadrenergic POTS

• Hyperadrenergic POTS is diagnosed when a patient meets general POTS criteria (heart rate increase ≥30 bpm or exceeding 120 bpm within 10 minutes of standing) PLUS demonstrates hyperadrenergic features 2
• The key diagnostic markers of hyperadrenergic POTS are:
  • Serum norepinephrine level ≥600 pg/mL upon standing 1
  • AND/OR an increase in systolic blood pressure ≥10 mmHg during head-up tilt test or standing 1
• The diagnosis requires the absence of orthostatic hypotension (defined as systolic BP drop ≥20 mmHg or diastolic BP drop ≥10 mmHg within 3 minutes of standing) 2, 3

Testing Protocol

• Perform a 10-minute active stand test with continuous monitoring of vital signs 3
  • Measure blood pressure and heart rate after 5 minutes of lying supine
  • Record measurements immediately upon standing, and at 2,5, and 10 minutes after standing
  • Patient must stand quietly for the full 10 minutes as heart rate increase may take time to develop
• Draw blood for catecholamine levels (specifically norepinephrine) while the patient is standing 1, 4
• Head-up tilt table testing can be used as an alternative to active standing test, particularly if the active stand test is inconclusive 2, 3

Clinical Features Suggesting Hyperadrenergic POTS

• Patients with hyperadrenergic POTS typically present with more pronounced symptoms compared to other POTS subtypes 4:
  • More frequent dizziness and headaches 4
  • Tremulousness or tremor 4
  • Palpitations and anxiety 3, 5
  • Greater increases in both heart rate and systolic blood pressure during orthostatic testing 4
• These patients often have symptoms suggestive of sympathetic overactivation 5:
  • Excessive sweating
  • Cold or clammy extremities
  • Pupillary dilation

Important Testing Considerations

• Testing should be performed in a quiet environment with temperature controlled between 21-23°C 3
• Patients should be fasted for 3 hours before the test 3
• Avoid nicotine, caffeine, theine, or taurine-containing drinks on the day of examination 3
• Tests should ideally be performed before noon 3
• Medications that might affect autonomic function should be discontinued before testing when possible 3

Common Pitfalls in Diagnosis

• Failure to perform the active stand test for the full 10 minutes may miss delayed heart rate increases 3
• Not distinguishing hyperadrenergic POTS from neuropathic POTS can lead to suboptimal treatment approaches 1, 5
• Failing to measure serum norepinephrine levels while standing can miss the diagnosis 1, 4
• Not considering the hyperadrenergic subtype when standard POTS treatments fail 1
• Confusing hyperadrenergic POTS with anxiety disorders due to overlapping symptoms 5

Treatment Implications

• Identifying hyperadrenergic POTS is clinically important as these patients often respond differently to standard POTS treatments 1
• Patients with hyperadrenergic POTS may benefit from specific treatments targeting the hyperadrenergic state, such as ivabradine 6
• These patients are often more difficult to treat and may require multiple medication combinations 1