What are the causes of orthostatic hypotension and which laboratory investigations should be ordered?

Causes of Orthostatic Hypotension and Laboratory Investigations

Direct Answer

Medications—particularly diuretics, vasodilators, alpha-blockers, and psychotropic drugs—are the most common cause of orthostatic hypotension, followed by autonomic dysfunction from conditions like diabetes and Parkinson's disease. 1 For laboratory workup, obtain a complete metabolic panel (electrolytes, BUN, creatinine, glucose), complete blood count, and hemoglobin A1c to assess for volume depletion, anemia, and diabetes-related autonomic neuropathy. 1, 2

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Primary Causes (Algorithmic Approach)

1. Medication-Induced (Most Common)

Start by reviewing all medications, as this is the most frequent and reversible cause:

• Diuretics cause volume depletion and are among the most common culprits 1
• Vasodilators (including nitrates) directly reduce vascular tone 1
• Alpha-adrenergic blockers impair vasoconstriction, particularly problematic with first doses 1, 3
• Beta-blockers can worsen orthostatic symptoms 1
• Psychotropic medications (phenothiazines, tricyclic antidepressants, MAO inhibitors) have significant incidence of orthostatic hypotension 3
• Cardiovascular drugs including dopamine agonists, antianginals, and antiarrhythmics 3

2. Autonomic Nervous System Dysfunction (Neurogenic)

If medications are not the cause, consider autonomic failure:

Primary Autonomic Failure:

• Multiple system atrophy with widespread autonomic degeneration 1
• Pure autonomic failure affecting peripheral autonomic nerves 1
• Parkinson's disease 1
• Dementia with Lewy bodies 1

Secondary Autonomic Failure:

• Diabetes mellitus causing autonomic neuropathy (leading secondary cause) 1
• Amyloidosis with autonomic nerve infiltration 1
• Spinal cord injuries 1
• Auto-immune or paraneoplastic autonomic neuropathy 1

Key distinguishing feature: Neurogenic orthostatic hypotension shows a blunted heart rate response (<10 bpm increase) upon standing due to impaired autonomic control. 1, 2

3. Volume Depletion and Hypovolemia (Non-Neurogenic)

• Severe volume depletion from excessive diuresis, dehydration, or blood loss 1
• Key distinguishing feature: Non-neurogenic causes show a preserved or enhanced heart rate response upon standing 1, 2

4. Cardiovascular Causes

• Severe arteriosclerosis causing pseudohypertension 1
• Cardiac insufficiency or decreased cardiac output (contributory, not primary defect) 1

5. Age-Related Physiologic Changes

• Stiffer hearts less responsive to preload changes 1
• Impaired compensatory vasoconstrictor reflexes 1
• Baroreflex dysfunction 1
• Reduced cerebral autoregulation 1
• Prevalence: approximately 7% in men over 70 years, associated with 64% increase in age-adjusted mortality 1

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Laboratory Investigations to Order

Essential Initial Labs:

• Complete Metabolic Panel (electrolytes, BUN, creatinine, glucose) to assess for:

  • Volume depletion (elevated BUN/creatinine ratio) 4, 5
  • Electrolyte abnormalities from diuretic use 1
  • Renal function 5

• Complete Blood Count (CBC) to evaluate for:

  • Anemia causing reduced oxygen-carrying capacity 4, 5
  • Blood loss as a cause of hypovolemia 5

• Hemoglobin A1c to screen for:

  • Diabetes mellitus, the leading secondary cause of autonomic neuropathy 1

Additional Labs Based on Clinical Suspicion:

• Thyroid function tests (TSH, free T4) if endocrine dysfunction suspected 5
• Cortisol level if adrenal insufficiency suspected 5
• Vitamin B12 level if peripheral neuropathy suspected 4
• Serum and urine protein electrophoresis if amyloidosis suspected (look for autonomic symptoms plus cardiac or renal involvement) 1

Specialized Testing (Not Routine Labs):

• ECG to rule out arrhythmias contributing to symptoms 2
• Echocardiography only if cardiac cause suspected with clinical evidence of cardiac disease (low diagnostic yield otherwise) 2
• 24-hour ambulatory blood pressure monitoring to detect patterns of BP variability and supine hypertension 2
• Head-up tilt-table testing when standard orthostatic vital signs are nondiagnostic or to assess treatment response in autonomic disorders 5

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Critical Diagnostic Pitfalls to Avoid

• Don't assume asymptomatic orthostatic hypotension requires treatment cessation: In hypertensive patients, asymptomatic orthostatic hypotension during treatment should not trigger automatic down-titration, as intensive BP lowering actually reduces orthostatic hypotension risk by improving baroreflex function 1

• Pseudohypertension in elderly: Calcified arteries may lead to falsely elevated BP readings, resulting in overtreatment and iatrogenic orthostatic hypotension 2

• Timing matters: Extend standing time beyond 3 minutes if symptoms suggest orthostatic hypotension but initial testing is negative (delayed orthostatic hypotension) 2

• Symptoms depend on absolute BP level, not just the magnitude of drop: Focus on symptom relief rather than arbitrary BP goals 2, 6

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Proper Measurement Technique for Diagnosis

• Patient rests supine or sitting for 5 minutes before baseline measurement 2
• Measure BP in both arms at initial visit; use arm with higher reading if difference >10 mmHg 2
• Measure BP and heart rate at 1 minute and 3 minutes after standing 2
• Use validated device with appropriate cuff size at heart level 2
• Patient should fast for 3 hours and avoid nicotine/caffeine before testing 2
• Testing in temperature-controlled environment (21-23°C) 2

Diagnostic criteria: Sustained decrease in systolic BP ≥20 mmHg, diastolic BP ≥10 mmHg, or systolic BP <90 mmHg within 3 minutes of standing 2