What laboratory tests are recommended for patients presenting with low energy and fatigue?

Laboratory Tests for Low Energy and Fatigue

For patients presenting with low energy and fatigue, initial laboratory evaluation should include complete blood count (CBC), comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), iron studies (including plasma iron, transferrin, transferrin saturation, and ferritin), inflammatory markers (ESR and CRP), and vitamin D level. 1

Initial Assessment and Screening

Before ordering laboratory tests, assess fatigue severity using a validated scale:

• Use a 0-10 visual analog scale where:
  • 0-3 indicates mild fatigue (minimal intervention needed)
  • 4-10 indicates moderate to severe fatigue (requires comprehensive evaluation)
  • ≥7 is associated with marked decrease in physical functioning 2, 1

First-Line Laboratory Tests

For patients with moderate to severe fatigue (score ≥4), order:

1. Complete Blood Count (CBC) with differential

   • Evaluates for anemia, infection, and other hematologic abnormalities 1

2. Comprehensive Metabolic Panel (CMP)

   • Includes electrolytes, blood urea nitrogen, serum creatinine, liver function tests, and glucose
   • Screens for metabolic abnormalities, liver or kidney dysfunction 1

3. Thyroid Function Tests

   • TSH as primary screening test
   • Add free T4 if TSH is abnormal 1

4. Iron Studies

   • Plasma iron, transferrin, transferrin saturation, and ferritin
   • Important as iron deficiency can cause fatigue even without anemia 1

5. Inflammatory Markers

   • ESR and CRP to screen for inflammatory conditions 1

6. Vitamin D Level

   • Particularly important in patients with risk factors for deficiency 1

7. Urinalysis

   • Screens for infection, kidney disease, and diabetes 1

Additional Testing Based on Clinical Suspicion

Consider these additional tests when specific conditions are suspected:

• Suspected cardiac issues:

  • BNP or NT-proBNP
  • ECG and chest radiograph
  • Electrolytes including calcium and magnesium 1

• Suspected autoimmune disease:

  • Autoimmune markers (ANA, RF, etc.) 1

• Suspected sleep disorders:

  • Sleep study referral if symptoms suggest sleep apnea or other sleep-related breathing disorders 3

Interpretation and Follow-up

• Normal laboratory values do not exclude fatigue-causing conditions 1
• The presence of an abnormal laboratory result does not necessarily indicate the cause of fatigue 4
• If initial testing is normal but fatigue persists, consider:
  • Psychological evaluation (depression and anxiety are common causes) 3
  • Expanded testing based on any new or evolving symptoms 1

Important Considerations

• Laboratory abnormalities are found in only about 5% of patients with chronic fatigue 5
• Depression, sleep disorders, and excessive psychosocial stress are the most common causes of persistent fatigue (18.5% for depression) 3
• Previously undiagnosed cancer is a rare cause (0.6%) of fatigue 3
• Consider energy and fatigue as potentially independent states that may require different assessment approaches 6

Common Pitfalls to Avoid

• Overreliance on laboratory testing: Excessive testing rarely yields additional diagnoses and may lead to unnecessary interventions 4, 5
• Neglecting psychological causes: Psychological factors are among the most common causes of fatigue but are often overlooked 3
• Failure to reassess: If initial testing is normal but symptoms persist, scheduled follow-up is essential to prevent overdiagnosis while ensuring appropriate care 3

Remember that while laboratory testing is an important component of fatigue evaluation, the diagnostic yield of extensive testing in patients with chronic fatigue is relatively low. A targeted approach based on clinical presentation is most efficient and cost-effective.