What is the recommended workup and treatment for Postural Orthostatic Tachycardia Syndrome (POTS)?

POTS Workup

Diagnostic Criteria

POTS is diagnosed by demonstrating a sustained heart rate increase of ≥30 bpm (≥40 bpm in adolescents aged 12-19 years) within 10 minutes of standing, in the absence of orthostatic hypotension, accompanied by symptoms of orthostatic intolerance. 1, 2

• Standing heart rate often exceeds 120 bpm 1, 2
• Orthostatic hypotension must be explicitly absent (defined as systolic BP drop ≥20 mmHg or diastolic BP drop ≥10 mmHg within 3 minutes of standing) 1, 2
• Symptoms must worsen upon standing and improve when sitting or lying down 2

Initial Diagnostic Testing Protocol

10-Minute Active Stand Test (First-Line)

Perform a 10-minute active stand test with continuous monitoring as the primary diagnostic approach. 1, 2

• Measure blood pressure and heart rate after 5 minutes of lying supine 1
• Record immediately upon standing, then at 2,5, and 10 minutes after standing 1
• Patient must stand quietly for the full 10 minutes—heart rate increase may be delayed 1, 2
• Document all symptoms occurring during the test 1

Testing Conditions (Critical)

• Perform in a quiet environment with temperature controlled between 21-23°C 1, 2
• Patient must fast for 3 hours before testing 1, 2
• Avoid nicotine, caffeine, theine, or taurine-containing drinks on the day of examination 1, 2
• Ideally perform testing before noon 1

Common Pitfall: Failing to perform the full 10-minute stand test may miss delayed heart rate increases. 2

Essential Laboratory and Cardiac Workup

Mandatory Initial Tests

• 12-lead ECG to rule out arrhythmias or conduction abnormalities 1, 2
• Thyroid function tests to exclude hyperthyroidism 1, 2
• Comprehensive medication review, especially cardioactive drugs 1, 2
• Detailed medical history including family history of similar conditions 1, 2

Tilt-Table Testing (When Indicated)

• Perform tilt-table testing if the active stand test is inconclusive or negative despite high clinical suspicion 1, 2

Symptom Evaluation

Core Orthostatic Symptoms to Document

• Dizziness and light-headedness 2
• Palpitations and sinus tachycardia 2
• Generalized weakness, fatigue, and lethargy 2
• Visual disturbances (blurring, tunnel vision) 2
• Cognitive difficulties ("brain fog") 2
• Headache and chest pain 2
• Gastrointestinal dysfunction 2

Expanded Workup for Atypical POTS

Red Flags Requiring Additional Testing

Consider expanded workup if patient has: 3

• Older age at onset or male sex 3
• Prominent syncope 3
• Examination abnormalities other than joint hyperextensibility 3
• Disease refractory to nonpharmacological and first-line treatments 3

Additional Testing for Atypical Cases

• Autonomic function testing including tilt table or sudomotor testing 4, 3
• Autoantibody testing if POTS is confirmed 4
• Neuropathy workup if peripheral denervation suspected 3
• Consider Guillain-Barré syndrome evaluation in appropriate clinical context 3

Screening for Comorbid Conditions

When POTS is Confirmed

Evaluate for commonly associated conditions, particularly in patients with joint hypermobility or gastrointestinal symptoms: 4, 2

Mast Cell Activation Syndrome (MCAS)

• Obtain baseline serum tryptase level 4
• If MCAS suspected, collect tryptase levels at baseline and 1-4 hours following symptom flares 4
• Diagnostic threshold: increase of 20% above baseline plus 2 ng/mL 4
• Refer to allergy specialist or mast cell disease research center if diagnosis supported 4

Gastrointestinal Evaluation

• Celiac disease testing should be considered earlier in patients with hEDS/HSDs and various GI symptoms 4
• Gastric motor function testing (gastric emptying and/or accommodation) should be considered in patients with chronic upper GI symptoms, as abnormal gastric emptying may be more common than in the general population 4
• Anorectal manometry, balloon expulsion test, or defecography for incomplete evacuation symptoms, given high prevalence of pelvic floor dysfunction 4

Associated Conditions to Screen For

• Deconditioning 5, 2
• Chronic fatigue syndrome 5, 2
• Joint hypermobility syndrome/hypermobile Ehlers-Danlos syndrome 4, 2
• Post-viral syndromes 2
• Depression and anxiety 2

Common Diagnostic Pitfalls

• Not distinguishing POTS from inappropriate sinus tachycardia or other tachyarrhythmias 1, 2
• Testing under improper conditions (not fasting, caffeine intake, wrong temperature) can affect results and lead to misdiagnosis 2
• For heart rates reaching 180 bpm, perform cardiac evaluation to rule out other arrhythmias before attributing symptoms solely to POTS 5

Phenotype Identification for Treatment Planning

Identify the predominant pathophysiologic mechanism(s) to guide treatment: 6, 7

• Neuropathic POTS: Peripheral denervation with impaired vasoconstriction 6, 7
• Hypovolemic POTS: Low blood volume, often with dehydration and deconditioning 6, 7
• Hyperadrenergic POTS: Excessive norepinephrine production or impaired reuptake 6, 7