What blood workup is recommended for a patient presenting with hypersomnia and Postural Orthostatic Tachycardia Syndrome (POTS)?

Blood Workup for Hypersomnia and POTS

For patients with hypersomnia and Postural Orthostatic Tachycardia Syndrome (POTS), a comprehensive blood workup should include thyroid function tests, complete blood count, basic metabolic panel, liver function tests, and serum tryptase levels to evaluate for underlying medical conditions that may contribute to symptoms.

Core Laboratory Tests for Hypersomnia

• Thyroid stimulating hormone (TSH) to rule out thyroid disorders that may cause hypersomnia 1
• Complete blood count (CBC) to identify anemia or other hematologic abnormalities that could contribute to fatigue 1
• Basic metabolic panel including electrolytes, glucose, and renal function to identify metabolic disturbances 1
• Liver function tests to evaluate for hepatic dysfunction that may affect sleep quality 1

Specific Tests for POTS Evaluation

• Serum electrolytes with particular attention to potassium levels, as hypokalemia can affect cardiac function and exacerbate POTS symptoms 1
• Aldosterone-to-renin ratio to rule out primary aldosteronism, which can present with symptoms similar to POTS 1
• Serum tryptase levels (baseline and during symptom flares) to evaluate for mast cell activation syndrome (MCAS), which commonly co-occurs with POTS 1
  • An increase of 20% above baseline plus 2 ng/mL during symptom flares is necessary to demonstrate evidence of mast cell activation 1

Additional Tests to Consider

• Fasting glucose to rule out hypoglycemia, which can present with hypersomnia (as seen in cases of insulinoma) 2
• Iron studies including ferritin to evaluate for iron deficiency, which can contribute to restless legs syndrome and sleep disruption 1
• Autoimmune markers in patients with suspected autoimmune dysautonomia underlying POTS 1
• 24-hour urinary sodium to assess sodium intake, which is important in POTS management 1

Diagnostic Approach Algorithm

1. First tier testing (for all patients with hypersomnia and POTS):

   • TSH, CBC, comprehensive metabolic panel, liver function tests 1
   • Baseline serum tryptase 1

2. Second tier testing (based on clinical presentation):

   • If orthostatic symptoms predominate: Aldosterone-to-renin ratio, 24-hour urinary sodium 1
   • If allergic or mast cell activation symptoms present: Serum tryptase during symptom flares 1
   • If excessive daytime sleepiness is severe: Consider cerebrospinal fluid hypocretin levels (especially if cataplexy is present) 1

Important Clinical Considerations

• Blood tests should be interpreted in conjunction with clinical findings and specialized testing such as polysomnography (PSG) followed by multiple sleep latency test (MSLT) for hypersomnia diagnosis 1, 3
• Autonomic testing including tilt table testing is essential for confirming POTS diagnosis (heart rate increase ≥30 bpm within 10 minutes of standing) 1
• Many patients with POTS have sleep disturbances that may contribute to hypersomnia symptoms, making the diagnostic workup particularly important 4, 5

Common Pitfalls to Avoid

• Failing to consider medication effects that may complicate interpretation of both sleep studies and autonomic testing in patients with hypersomnia and POTS 1, 3
• Overlooking the need for tryptase testing during symptom flares, as baseline levels may be normal in MCAS 1
• Not considering rare causes of hypersomnia such as insulinoma, which can present with symptoms similar to idiopathic hypersomnia 2
• Relying solely on laboratory tests without appropriate clinical correlation and specialized testing (PSG/MSLT for hypersomnia, tilt table for POTS) 1, 3