From the Guidelines
To rule out secondary causes of paresthesias, I recommend a comprehensive laboratory workup including complete blood count (CBC), comprehensive metabolic panel (CMP), hemoglobin A1c, thyroid function tests (TSH, free T4), vitamin B12 level, folate level, serum protein electrophoresis (SPEP), and erythrocyte sedimentation rate (ESR). This approach is based on the most recent evidence from the American Diabetes Association, as outlined in the 2023 standards of care in diabetes 1. The following tests are essential to identify common causes of paresthesias:
- Complete blood count (CBC) to rule out anemia or infection
- Comprehensive metabolic panel (CMP) to assess electrolyte and renal function
- Hemoglobin A1c to diagnose or monitor diabetes
- Thyroid function tests (TSH, free T4) to evaluate thyroid dysfunction
- Vitamin B12 level to identify deficiency or insufficiency
- Folate level to assess for deficiency
- Serum protein electrophoresis (SPEP) to detect monoclonal gammopathies
- Erythrocyte sedimentation rate (ESR) to evaluate for inflammatory conditions Additional testing should include:
- Vitamin D level to assess for deficiency
- Heavy metal screening (particularly lead, mercury, and arsenic) to identify toxin exposures
- Antinuclear antibody (ANA) testing to evaluate for autoimmune conditions
- Rheumatoid factor to assess for rheumatoid arthritis or other autoimmune diseases In patients with specific risk factors, consider:
- HIV testing
- Hepatitis panel
- Lyme disease serology
- Vasculitis markers like ANCA The rationale for this comprehensive approach is that paresthesias often result from metabolic derangements, nutritional deficiencies, autoimmune conditions, or systemic diseases that affect peripheral nerves, as noted in the 2019 standards of care in diabetes 1 and the 2020 standards of care in diabetes 1. Early identification of these underlying causes allows for targeted treatment that may reverse or prevent progression of neurological symptoms, rather than simply managing the sensory disturbances symptomatically, as emphasized in the 2018 standards of care in diabetes 1 and the 2015 study on microvascular complications and foot care 1.
From the Research
Laboratory Tests for Paresthesias
To rule out secondary causes of paresthesias, several laboratory tests are recommended:
- Complete blood count 2, 3
- Comprehensive metabolic profile 2, 3
- Fasting blood glucose 2, 3
- Vitamin B12 levels 2, 3, 4
- Thyroid-stimulating hormone (TSH) levels 2, 3, 4
- Serum protein electrophoresis with immunofixation 2
- Blood cell count, thyroid, renal and liver function tests, blood glucose levels, HbA1c 3
Additional Tests
If the initial evaluation is inconclusive, additional tests may be considered:
Selection of Laboratory Tests
Laboratory tests should be selected specifically according to the suspected type of neuropathy to avoid unnecessary tests and expenses 3. The selection of tests should be based on the individual and family history, clinical presentation, and electrophysiological findings 3.