Which laboratory tests should I order to evaluate metabolic, nutritional, and endocrine causes of peripheral neuropathy and establish baseline safety before initiating gabapentin/pregabalin, duloxetine, or rosuvastatin?

Laboratory Testing for Peripheral Neuropathy Evaluation and Medication Safety

Order a comprehensive metabolic panel, fasting glucose, HbA1c, vitamin B12 with methylmalonic acid, TSH, serum protein electrophoresis with immunofixation, complete blood count, hepatic function panel (AST/ALT), and creatinine clearance before initiating treatment. 1, 2, 3, 4

Essential Metabolic and Endocrine Screening

Diabetes Assessment

• Fasting blood glucose – screens for undiagnosed diabetes mellitus, the most common cause of peripheral neuropathy affecting 206 million people worldwide 2, 3, 4
• Hemoglobin A1c – establishes baseline glycemic control and guides disease-modifying therapy, with target of 6-7% to prevent neuropathy progression 1, 3

Nutritional Deficiencies

• Vitamin B12 level with methylmalonic acid (and optionally homocysteine) – B12 deficiency causes or worsens neuropathy and is particularly important in patients on metformin, which interferes with B12 absorption 1, 2, 3, 4
• Folate and vitamin B6 levels – deficiencies contribute to neuropathy, though high-dose pyridoxine can paradoxically cause sensory neuron damage, especially with renal insufficiency 5, 1

Thyroid Function

• Thyroid-stimulating hormone (TSH) – hypothyroidism is a reversible cause of peripheral neuropathy and must be excluded 1, 6, 2, 4

Monoclonal Gammopathy Screening

• Serum protein electrophoresis with immunofixation – detects monoclonal gammopathies that underlie neuropathy in a significant proportion of cases 1, 2, 3, 4

Baseline Safety Laboratories Before Medication Initiation

Hepatic Function (Critical for Duloxetine)

• AST, ALT, total bilirubin, alkaline phosphatase – duloxetine is absolutely contraindicated in hepatic disease and requires baseline assessment 1, 7
• Duloxetine should be avoided entirely if any clinically significant hepatic impairment exists 1

Renal Function (Critical for Gabapentin/Pregabalin and Rosuvastatin)

• Serum creatinine and calculated creatinine clearance (CrCl) – both gabapentinoids require dose adjustment in renal impairment 1, 7
• Pregabalin is preferred when CrCl ≥60 mL/min without significant peripheral edema; otherwise consider duloxetine or tricyclic antidepressants 1
• Rosuvastatin requires dose adjustment and careful monitoring in renal impairment 1

Muscle Enzyme Assessment

• Creatine phosphokinase (CPK) – establishes baseline before statin therapy and helps evaluate myopathic causes of neuropathic symptoms 1

Complete Blood Count

• CBC with differential – screens for hematologic causes and establishes baseline before initiating medications 2, 4

Comprehensive Metabolic Panel

• Electrolytes, BUN, creatinine, glucose, calcium – identifies uremic neuropathy and metabolic derangements 1, 2, 4

Conditional Testing Based on Clinical Context

If Autoimmune Neuropathy Suspected

• Autoimmune serology panel (ANA, ESR, CRP, ANCA, anti-smooth muscle, SSA/SSB, RNP, anti-dsDNA) – ordered when clinical features suggest autoimmune etiology 1

If Guillain-Barré or Variant Suspected

• Anti-ganglioside antibodies (anti-GM1, anti-GQ1b) – tested when acute or subacute demyelinating neuropathy is considered 1, 6

If Infectious Etiology Possible

• Hepatitis B, C, and HIV serology – ordered if risk factors present or clinical suspicion exists 1, 6
• Lyme disease testing – in endemic areas with appropriate clinical history 1

If Malignancy-Associated Neuropathy Suspected

• Paraneoplastic antibody panel (ANNA-1/anti-Hu, anti-MAG) – when cancer-related neuropathy is a concern 1

Critical Pitfalls to Avoid

• Do not skip hepatic function testing before duloxetine – this is an absolute contraindication that cannot be overlooked 1, 7
• Do not prescribe pregabalin without assessing renal function – dose adjustment is mandatory in renal impairment to prevent toxicity 1, 7
• Do not overlook B12 testing in metformin users – metformin-associated B12 deficiency can worsen neuropathy and is easily correctable 1
• Do not order extensive autoimmune or paraneoplastic panels routinely – these should be reserved for atypical presentations or when initial evaluation is unrevealing 1
• Do not forget baseline CPK before rosuvastatin – establishes reference point for monitoring statin-induced myopathy 1

Monitoring Strategy After Treatment Initiation

• Repeat HbA1c every 3 months to assess glycemic control optimization 1
• Monitor hepatic function periodically on duloxetine if baseline values are borderline 1
• Reassess renal function if gabapentinoid doses are escalated or if clinical status changes 7
• Check CPK if muscle symptoms develop on rosuvastatin 1