What lab work is recommended for a patient presenting with paresthesia?

Laboratory Workup for Paresthesia

The laboratory evaluation for paresthesia should be guided by history and physical examination findings, with initial testing including complete blood count, comprehensive metabolic panel (including calcium and magnesium), fasting glucose or hemoglobin A1c, vitamin B12, and thyroid-stimulating hormone—routine extensive laboratory testing without clinical indication is not recommended. 1

Initial Targeted Laboratory Tests

The most cost-effective approach involves selective testing based on clinical presentation rather than routine comprehensive panels:

• Complete blood count (CBC): Identifies anemia, macrocytosis suggesting B12 deficiency, or hematologic malignancies 1
• Comprehensive metabolic panel: Detects renal dysfunction, electrolyte abnormalities (particularly calcium and magnesium), and hepatic disease 1
• Fasting blood glucose or hemoglobin A1c: Diabetes mellitus is the most common treatable cause of peripheral neuropathy presenting with paresthesia 1
• Vitamin B12 level: Nutritional deficiency is among the most common treatable causes 1
• Thyroid-stimulating hormone (TSH): Hypothyroidism represents another common treatable etiology 1
• Erythrocyte sedimentation rate (ESR): Screens for inflammatory or vasculitic processes 1

Clinical Context Determines Additional Testing

When Hypocalcemia is Suspected

If paresthesia presents with positive Chvostek's or Trousseau's signs, perioral numbness, or tetany:

• Serum calcium (corrected for albumin) and ionized calcium: Hypocalcemia below 8.4 mg/dL with symptoms requires treatment 2, 3
• Magnesium level: Hypomagnesemia can cause hypocalcemia and paresthesia 3
• Phosphorus and intact PTH: Helps differentiate causes of hypocalcemia 2
• 25-hydroxyvitamin D: Vitamin D deficiency is a common cause of hypocalcemia 3

When Mononeuropathy is Suspected

For localized paresthesia in specific nerve distributions (e.g., median nerve territory suggesting carpal tunnel syndrome):

• No routine laboratory testing is indicated if clinical presentation is classic 4, 5
• Nerve conduction studies and electromyography are more appropriate than laboratory tests 1
• Ultrasonography can identify nerve entrapment, enlargement, or anatomical variations 4

When Acute or Rapidly Progressive Paresthesia Occurs

For paresthesia developing over days, rapidly progressive, asymmetric, or associated with motor weakness:

• Lumbar puncture with cerebrospinal fluid analysis: Essential for diagnosing Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy 1
• Consider urgent neurology consultation before extensive laboratory workup 4

Specialized Testing (Only When Clinically Indicated)

These tests should not be ordered routinely but reserved for specific clinical scenarios:

• Serum protein electrophoresis with immunofixation: When monoclonal gammopathy is suspected (older patients, elevated total protein) 4
• Lyme disease serology: Only in endemic areas or with exposure history and suggestive clinical features 6
• HIV testing: When risk factors present or other systemic symptoms suggest immunodeficiency 6
• Heavy metal screening: Only with occupational exposure or other toxin exposure history 6
• Genetic testing: Reserved for suspected inherited neuropathies (family history, young age, slowly progressive course) 4

Common Pitfalls to Avoid

Do not order extensive "neuropathy panels" without clinical indication—this approach is costly, generates false positives requiring additional workup, and rarely changes management when history and examination are unrevealing 6. The yield of laboratory testing is extremely low in patients who have returned to baseline neurologic status without focal findings 6.

Do not assume all paresthesia requires laboratory investigation—carpal tunnel syndrome and other entrapment neuropathies are the most common causes of acroparesthesia and are diagnosed clinically 4, 5. Electrodiagnostic studies are more appropriate than laboratory tests in these cases 1.

Recognize that small fiber neuropathy may have normal nerve conduction studies and normal routine laboratory testing—if clinical suspicion is high despite negative initial workup, specialized testing (skin biopsy, autonomic testing) may be needed rather than additional blood tests 1.

Algorithm for Laboratory Testing

1. Obtain focused history: Duration (acute vs. chronic), distribution (symmetric vs. asymmetric, distal vs. proximal), associated symptoms (weakness, autonomic dysfunction), medical comorbidities (diabetes, renal disease, thyroid disease), medications, toxin exposures, family history 1

2. Perform thorough neurologic examination: Assess all cranial nerves, motor strength, reflexes, sensory modalities (pinprick, light touch, vibration, proprioception), signs of hypocalcemia (Chvostek's, Trousseau's) 6, 5

3. Order initial targeted laboratory panel if examination suggests polyneuropathy or systemic cause: CBC, CMP (including calcium and magnesium), fasting glucose or HbA1c, B12, TSH, ESR 1

4. Add specialized tests only when specific clinical features present: Lumbar puncture for acute/rapidly progressive cases, Lyme serology in endemic areas, protein electrophoresis for suspected paraproteinemia 6, 1

5. Proceed to electrodiagnostic studies if diagnosis remains unclear after initial laboratory evaluation or if localized neuropathy suspected 1