What laboratory tests should be ordered for a patient presenting with numbness of fingers to rule out underlying conditions?

Laboratory Workup for Finger Numbness

Order blood glucose, vitamin B12 with metabolites (methylmalonic acid and homocysteine), and serum protein immunofixation electrophoresis as your initial screening labs for finger numbness. 1, 2

Essential First-Line Laboratory Tests

The highest-yield screening tests for evaluating finger numbness include:

• Blood glucose/HbA1c: Diabetes is the most common metabolic cause of peripheral neuropathy, and up to 50% of diabetic neuropathy may be asymptomatic. 3, 1 Screen all patients regardless of symptoms.

• Vitamin B12 with metabolites: B12 deficiency accounts for 2.2-8% of polyneuropathy cases. 1 Critically, 5-10% of patients with low-normal B12 levels still have true deficiency detected only by elevated methylmalonic acid and homocysteine. 1 Always order metabolites, not just serum B12 alone.

• Serum protein immunofixation electrophoresis: Approximately 10% of patients with unexplained polyneuropathy have monoclonal gammopathy. 1 This test is more sensitive than standard serum protein electrophoresis for detecting small monoclonal proteins. 1, 2 IgG monoclonal gammopathies can cause sensory and proprioceptive neuropathies affecting the fingers. 1

Additional Testing Based on Clinical Context

If Ulnar Distribution (4th and 5th Digits Only)

When numbness is isolated to the ring and little fingers, this suggests ulnar nerve compression rather than systemic neuropathy. 4 In this scenario:

• The above metabolic screening is still warranted, as diabetes, hypothyroidism, and rheumatoid arthritis are risk factors for nerve entrapment. 5
• Consider electrodiagnostic studies to localize compression (cubital tunnel vs. Guyon's canal). 4

If Symmetric "Stocking-Glove" Distribution

When numbness affects all fingers bilaterally, expand your workup:

• TSH: Hypothyroidism is a recognized metabolic cause of polyneuropathy. 1, 5
• Comprehensive metabolic panel: Evaluate for chronic kidney disease and electrolyte abnormalities. 3
• Complete blood count: Screen for anemia, infection, or hematologic disorders. 3
• Vitamin B1, B6, folate, and vitamin E levels: Consider in patients with malnutrition, alcohol use, or unexplained neuropathy. 1

If Inflammatory or Immune-Mediated Features Suspected

When presentation includes acute/subacute onset, weakness, or systemic symptoms:

• CSF analysis: Elevated protein with normal cell count (albuminocytological dissociation) supports Guillain-Barré syndrome or CIDP, though protein is normal in 30-50% of GBS patients in the first week. 3, 2 Marked pleocytosis (>50 cells/μl) suggests alternative diagnoses like infection or malignancy. 3
• HIV, syphilis, Lyme serology: Screen for infectious causes based on risk factors and geographic exposure. 1
• Vasculitic/autoimmune panel: Consider ESR, CRP, ANA, RF, ANCA in appropriate clinical contexts. 2

If Atypical Features Present

• Heavy metal screening (lead, arsenic): Consider with occupational exposure or unexplained axonal neuropathy. 1
• Paraneoplastic antibody panel: Order when neuropathy is rapidly progressive or associated with constitutional symptoms suggesting malignancy. 1, 2

Common Pitfalls to Avoid

• Don't order B12 alone: Always include methylmalonic acid and homocysteine, as serum B12 can be falsely normal. 1
• Don't use standard protein electrophoresis: Serum protein immunofixation is significantly more sensitive for detecting monoclonal gammopathies. 1
• Don't wait for antibody results to treat: If GBS is suspected clinically, initiate treatment without waiting for antiganglioside antibody results, which have limited diagnostic value. 3
• Don't assume all finger numbness is carpal tunnel: Isolated 4th and 5th digit involvement suggests ulnar pathology, while all-digit involvement suggests systemic neuropathy requiring metabolic workup. 4

When Labs Are Unrevealing

Remember that 20-25% of chronic polyneuropathies remain idiopathic despite thorough evaluation. 1 In these cases, electrodiagnostic studies become essential to characterize the neuropathy pattern (axonal vs. demyelinating) and guide management even without identifying an underlying cause. 1