What is the recommended lab workup for a young to middle-aged patient with a history of autoimmune disorders, anxiety, or depression presenting with dizziness and Postural Orthostatic Tachycardia Syndrome (POTS)?

Lab Workup for Dizziness and POTS

In patients presenting with dizziness and suspected POTS, perform postural vital signs testing first (active stand test for 10 minutes), followed by targeted laboratory testing including thyroid function tests, complete blood count, comprehensive metabolic panel, and baseline serum tryptase if mast cell activation syndrome is suspected based on multi-system symptoms. 1, 2

Initial Diagnostic Testing

Postural Vital Signs Assessment (Active Stand Test)

• Measure blood pressure and heart rate after 5 minutes of lying supine, then immediately upon standing, and at 2,5, and 10 minutes after standing. 2
• The patient must stand quietly for the full 10 minutes as heart rate increase may take time to develop. 2
• POTS is diagnosed by a sustained heart rate increase of ≥30 beats/min (≥40 bpm in adolescents aged 12-19) within 10 minutes of standing, in the absence of orthostatic hypotension. 2
• Standing heart rate is often >120 bpm in POTS patients. 2
• Confirm absence of orthostatic hypotension (systolic BP drop ≥20 mmHg or diastolic BP drop ≥10 mmHg within 3 minutes). 2

Testing Conditions

• Perform testing in a quiet environment with temperature controlled between 21-23°C. 2
• Patients should be fasted for 3 hours before testing and avoid nicotine, caffeine, theine, or taurine-containing drinks on the day of examination. 2
• Tests should ideally be performed before noon. 2

Essential Laboratory Testing

Thyroid Function

• Obtain thyroid function tests (TSH, free T4) to exclude hyperthyroidism, which can mimic POTS symptoms. 2

Basic Metabolic Panel

• Complete blood count to assess for anemia or infection. 3
• Comprehensive metabolic panel to evaluate electrolyte abnormalities and renal function. 3

Medication Review

• Conduct a thorough medication review, especially cardioactive drugs that may cause tachycardia or orthostatic symptoms. 2

Targeted Testing for Associated Conditions

Assessment for Joint Hypermobility (hEDS/HSD)

• Incorporate the Beighton score for assessing joint hypermobility as a screening tool in patients with POTS and gastrointestinal symptoms. 1
• If the Beighton score is positive, consider applying 2017 diagnostic criteria for hypermobile Ehlers-Danlos syndrome or refer to appropriate specialist. 1
• This is particularly important as POTS frequently coexists with joint hypermobility syndrome. 1, 3

Mast Cell Activation Syndrome (MCAS) Testing

• Testing for MCAS should be targeted to patients presenting with episodic symptoms involving 2 or more physiological systems (cutaneous, GI, cardiac, respiratory, neuropsychiatric). 1
• Specific symptoms suggesting MCAS include: visceral and somatic pain, pruritus, flushing, sweating, urticaria, angioedema, wheezing, tachycardia, abdominal cramping, vomiting, nausea, diarrhea. 1
• If MCAS is suspected, obtain serum tryptase levels at baseline and 1-4 hours following symptom flares. 1
• Increases of 20% above baseline plus 2 ng/mL are necessary to demonstrate evidence of mast cell activation. 1
• Universal testing for MCAS in all patients with POTS is not supported by current evidence. 1

Additional Cardiac Evaluation

Electrocardiogram

• Obtain a 12-lead ECG to rule out arrhythmias or conduction abnormalities. 2
• This helps distinguish POTS from inappropriate sinus tachycardia or other tachyarrhythmias. 2

Advanced Autonomic Testing

• Consider referral for tilt-table testing if the active stand test is inconclusive despite high clinical suspicion. 2
• Referral to cardiology or neurology for comprehensive autonomic function testing should be considered in patients with refractory symptoms after exclusion of medication side effects and appropriate lifestyle modifications (adequate hydration, physical exercise). 1

Autoimmune Evaluation in Select Cases

When to Consider Autoimmune Testing

• In patients with viral-like prodrome preceding symptoms or family history of autoimmune disorders, consider autoimmune evaluation. 4
• Growing evidence suggests POTS may be an autoimmune disorder in many cases, with elevated G-protein coupled receptor autoantibodies found in 89% of patients (alpha-1 adrenergic receptor) and 53% (muscarinic M4 receptor). 4
• However, routine autoimmune testing is not yet standard practice and should be reserved for research settings or severe refractory cases. 5

Common Pitfalls to Avoid

• Failing to perform the active stand test for the full 10 minutes may miss delayed heart rate increases. 2
• Not distinguishing POTS from orthostatic hypotension, inappropriate sinus tachycardia, or anxiety disorders leads to misdiagnosis. 2, 6, 7
• Using adult heart rate criteria (≥30 bpm) instead of pediatric criteria (≥40 bpm for ages 12-19) leads to overdiagnosis in adolescents. 2
• Failing to exclude secondary causes such as dehydration, medications, primary anxiety disorder, or eating disorders can lead to misdiagnosis. 2
• Not maintaining proper fasting conditions can affect test results and lead to inaccurate diagnosis. 2

Differential Diagnosis Considerations

Key Conditions to Exclude

• Orthostatic hypotension (BP drop >20 mmHg systolic or >10 mmHg diastolic within 3 minutes). 2
• Anxiety or panic disorder (though these frequently coexist with POTS). 1, 7
• Vestibular disorders including benign paroxysmal positional vertigo, vestibular neuritis, or Ménière's disease. 1
• Cardiac arrhythmias or structural heart disease. 2
• Medication side effects, particularly from alpha-adrenergic blocking agents. 8