What initial laboratory tests should be ordered for an adult patient presenting with new‑onset unexplained paresthesias?

Laboratory Workup for New-Onset Paresthesias

For an adult presenting with unexplained new-onset paresthesias, order serum glucose, sodium, vitamin B12, thyroid-stimulating hormone (TSH), and a complete metabolic panel as your initial laboratory evaluation.

Essential First-Line Laboratory Tests

The following tests should be obtained in every patient with new-onset paresthesias, as they identify the most common and treatable metabolic causes:

• Serum glucose – Hypoglycemia and diabetes mellitus are among the most frequent metabolic causes of peripheral neuropathy and paresthesias 1, 2
• Serum sodium and electrolytes – Hyponatremia and other electrolyte disturbances commonly manifest with neurological symptoms including paresthesias 1, 2
• Complete metabolic panel – Evaluates renal and hepatic function, as metabolic derangements frequently cause or exacerbate neuropathic symptoms 3, 4
• Thyroid-stimulating hormone (TSH) – Hypothyroidism is a well-established treatable cause of peripheral neuropathy 3
• Vitamin B12 level – Nutritional deficiencies, particularly B12 deficiency, are common causes of peripherally induced paresthesias 5

Targeted Second-Tier Testing Based on Clinical Context

Order these tests when specific clinical features suggest particular etiologies:

• Calcium and magnesium levels – Obtain in patients with known malignancy, renal failure, or alcohol use, as these electrolyte abnormalities can precipitate paresthesias 1, 3
• Complete blood count (CBC) – Evaluate for infection, anemia, or hematologic abnormalities that may contribute to neuropathic symptoms 3
• Erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA) – Consider when inflammatory or connective tissue diseases are suspected as causes of peripheral neuropathy 4
• Toxicology screening – Order when substance use, withdrawal, or medication toxicity is suspected, though routine screening has limited yield without clinical suspicion 1, 3
• Pregnancy test – Required for all women of childbearing age, as this affects diagnostic and treatment decisions 1, 3

When to Consider Lumbar Puncture

Lumbar puncture is not routinely indicated for isolated paresthesias but should be performed when:

• Fever, altered mental status, or meningeal signs suggest CNS infection 1
• Immunocompromised status raises concern for opportunistic infection 1
• Elevated CSF protein and pleocytosis may help diagnose inflammatory neuropathies, though this is typically pursued after initial metabolic workup is unrevealing 6, 7

When to Prioritize Neuroimaging Over Additional Labs

Obtain brain MRI (preferred) or CT head if focal neurological deficits, signs of stroke, or structural disease are present – neuroimaging should take precedence over extensive laboratory testing in these scenarios 8, 1, 3. MRI is more sensitive than CT for detecting subtle structural lesions that may cause paresthesias 1.

Common Pitfalls to Avoid

• Do not order extensive "shotgun" laboratory panels when history and examination do not suggest a specific alternative cause – this leads to false positives, unnecessary follow-up testing, and delayed diagnosis 8
• Do not overlook medication-induced causes – many drugs (chemotherapy agents, antiretrovirals, statins) cause peripheral neuropathy; a thorough medication history is essential 5
• Do not assume all paresthesias are peripheral – central nervous system lesions (stroke, demyelination, spinal cord compression) can present with paresthesias and require imaging rather than laboratory workup 5
• Do not delay vitamin B12 testing – B12 deficiency is a reversible cause of neuropathy, but prolonged deficiency can lead to irreversible nerve damage 5

Clinical Context Determines Laboratory Strategy

The pattern of paresthesias guides your workup:

• Symmetric distal "stocking-glove" distribution suggests metabolic or toxic neuropathy – prioritize glucose, B12, TSH, renal function 5
• Asymmetric or focal paresthesias suggest entrapment neuropathy or structural lesion – consider imaging before extensive labs 5
• Paresthesias with weakness require creatine kinase, ESR, and consideration of neuromuscular junction disorders 4
• Paresthesias with cognitive changes or encephalopathy warrant autoimmune encephalitis workup (serum and CSF autoantibodies) after metabolic causes are excluded 9