Laboratory Investigation of POTS
All patients with suspected POTS require a core laboratory panel including complete blood count, basic metabolic panel, thyroid function tests, and HbA1c, with additional cardiovascular biomarkers (BNP, calcium, magnesium) to rule out secondary causes and guide treatment. 1
Essential First-Tier Laboratory Tests
The initial laboratory workup should be comprehensive yet targeted:
- Complete blood count (CBC) to identify anemia, which commonly contributes to orthostatic symptoms or exacerbates POTS presentation 1, 2
- Basic metabolic panel to assess electrolyte abnormalities (particularly potassium) and renal function that directly affect cardiovascular regulation 1, 2, 3
- Thyroid function tests (TSH) are mandatory in all patients because thyroid disorders frequently mimic or worsen POTS symptoms 1, 2, 3
- Hemoglobin A1c (HbA1c) to screen for diabetes mellitus, which causes autonomic dysfunction 1, 2
Cardiovascular-Specific Biomarkers
These tests help identify cardiac causes and assess volume status:
- Brain natriuretic peptide (BNP) identifies cardiac causes of symptoms and evaluates for hypovolemic states, which is a major pathophysiologic mechanism in POTS 1, 2
- Serum electrolytes including calcium and magnesium are critical for cardiac conduction and muscle function 1, 2
Second-Tier Testing Based on Clinical Presentation
When specific clinical features suggest additional pathophysiology:
- 24-hour urinary sodium to objectively assess sodium intake, which is crucial for POTS management given that hypovolemia is a major mechanism 3
- Aldosterone-to-renin ratio when primary aldosteronism is suspected, as it can present with POTS-like symptoms 3
- Serum tryptase levels (baseline and during symptom flares 1-4 hours after exacerbations) when mast cell activation syndrome is suspected—an increase of 20% above baseline plus 2 ng/mL demonstrates mast cell activation 2, 3
- Iron studies including ferritin if restless legs syndrome or iron deficiency is suspected as a contributing factor 3
Important Clinical Caveats
Avoid ordering comprehensive panels without specific clinical indications—laboratory testing should be targeted based on your clinical assessment rather than reflexive ordering 1, 2. This approach is more cost-effective and reduces false-positive results that lead to unnecessary workup.
The laboratory evaluation must be interpreted alongside the diagnostic orthostatic testing (10-minute active stand test or tilt-table test), as POTS is fundamentally a clinical diagnosis requiring demonstration of sustained heart rate increase ≥30 bpm (≥40 bpm in adolescents 12-19 years) within 10 minutes of standing without orthostatic hypotension 2, 4, 5.
Follow-up laboratory monitoring may be necessary to assess treatment effects, particularly electrolytes if patients are on medications affecting fluid balance or following high-salt diet recommendations 1.