What is the diagnostic workup for a patient with hypertension and peripheral neuropathy symptoms, including numbness and tingling in fingers and toes?

Diagnostic Workup for Hypertension with Peripheral Neuropathy

The diagnostic workup for a patient presenting with elevated blood pressure and numbness/tingling in fingers and feet should begin with screening for diabetes mellitus, as this is the most common cause of this presentation, followed by evaluation for other secondary causes of hypertension and peripheral neuropathy.

Initial Assessment

Blood Pressure Evaluation

• Confirm hypertension with multiple readings on different occasions
• Perform ambulatory BP monitoring to rule out white-coat hypertension 1
• Assess for signs of malignant hypertension (BP ≥180/110 mmHg with acute organ damage) 1

Peripheral Neuropathy Assessment

• Comprehensive neurological examination focusing on:
  • Sensory testing using 10-g monofilament, pinprick sensation, vibration perception (128-Hz tuning fork), and ankle reflexes 2
  • Motor strength assessment
  • Assessment for autonomic symptoms (orthostatic hypotension, gastroparesis, etc.) 2
• Document distribution pattern (stocking-glove distribution suggests length-dependent neuropathy) 2

Laboratory Testing

Metabolic Workup

• Fasting blood glucose and HbA1c (diabetes is the most common cause of peripheral neuropathy) 2
• Comprehensive metabolic panel including:
  • Renal function (BUN, creatinine, eGFR) 2
  • Electrolytes (hypokalemia may suggest primary aldosteronism) 1
  • Liver function tests 2
• Lipid profile (dyslipidemia is common in patients with hypertension) 2
• Urinalysis and urine albumin-to-creatinine ratio (to assess for kidney damage) 2
  • Two of three samples should be abnormal (>30 mg/g) to confirm albuminuria 2

Secondary Hypertension Screening

• Aldosterone-to-renin ratio (for primary aldosteronism) 1
• TSH (for thyroid dysfunction) 1
• 24-hour urinary metanephrines (for pheochromocytoma) 1
• Consider lead levels if occupational exposure or risk factors present 3

Neuropathy Workup

• Vitamin B12, folate levels
• Hemoglobin A1c (if not already done)
• Consider testing for:
  • Inflammatory markers (ESR, CRP)
  • Serum protein electrophoresis (for paraproteinemia)
  • HIV testing (if risk factors present)

Imaging and Special Studies

Cardiovascular Assessment

• 12-lead ECG (to assess for left ventricular hypertrophy)
• Echocardiogram (to evaluate for cardiac structural changes from hypertension)
• Renal ultrasound with Doppler (to evaluate for renovascular hypertension) 1
  • Consider CT/MR angiography if ultrasound suggests renovascular disease 1

Neurophysiological Testing

• Nerve conduction studies and electromyography to:
  • Confirm peripheral neuropathy
  • Determine if sensory, motor, or mixed
  • Assess for axonal versus demyelinating pattern 2
  • Evaluate severity and distribution

Sleep Study

• Consider polysomnography if symptoms of obstructive sleep apnea present (common in resistant hypertension) 1

Additional Specialized Testing

Vascular Assessment

• Ankle-brachial index (ABI) if peripheral arterial disease is suspected 2
  • Consider in patients >50 years or with diabetes duration >10 years 2
• Segmental limb pressure measurements with pulse volume recordings if ABI abnormal 2

Autonomic Function Testing

• If symptoms of autonomic dysfunction are present:
  • Orthostatic blood pressure measurements
  • Heart rate variability testing
  • Quantitative sudomotor axon reflex test (QSART)

Tissue Sampling

• Consider skin biopsy with intraepidermal nerve fiber density assessment for small fiber neuropathy
• Consider nerve biopsy in atypical cases (rarely needed)

Diagnostic Algorithm

1. First, establish the diagnosis and severity of both hypertension and peripheral neuropathy
2. Screen for diabetes as the common underlying cause
3. If diabetes is present, optimize glycemic control as this can prevent or delay diabetic peripheral neuropathy 2
4. If diabetes is absent or neuropathy seems disproportionate to glycemic control, investigate for other causes
5. Evaluate for secondary causes of hypertension, particularly those that can also cause neuropathy (e.g., pheochromocytoma)
6. Consider the possibility of combined pathologies (hypertension and diabetes together worsen neuropathy) 4

Common Pitfalls to Avoid

• Attributing neuropathy solely to diabetes without considering other causes
• Missing secondary causes of hypertension that may require specific treatment
• Failing to assess for autonomic neuropathy, which can cause orthostatic hypotension and complicate hypertension management
• Not considering medication side effects as potential causes of neuropathy or hypertension
• Delaying treatment while completing diagnostic workup (treatment should begin promptly while evaluation continues)

Remember that hypertension and diabetes together compound peripheral nerve damage through combined mechanisms of ischemia and metabolic injury 4, making aggressive management of both conditions essential for preventing progression of neuropathy.