What general laboratory tests are recommended for patients presenting with fatigue?

Laboratory Tests for Fatigue Evaluation

For patients presenting with fatigue, initial laboratory evaluation should include a comprehensive metabolic panel (CMP), complete blood count (CBC) with differential, thyroid-stimulating hormone (TSH), urinalysis, inflammatory markers (ESR and CRP), and lipid profile. 1

Initial Laboratory Workup

First-line Tests

• Complete Blood Count (CBC) with differential

  • Evaluates for anemia, infection, and hematologic abnormalities 1, 2
  • Anemia is a common cause of fatigue that requires further investigation 2

• Comprehensive Metabolic Panel (CMP)

  • Includes electrolytes, BUN, creatinine, liver function tests, and glucose 1
  • Helps identify metabolic abnormalities, liver dysfunction, kidney disease, and diabetes 1

• Thyroid Function Tests

  • TSH is the primary screening test 1
  • Free T4 should be added if TSH is abnormal 1
  • Hypothyroidism is a common medical cause of fatigue 3

• Inflammatory Markers

  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 1
  • Helps screen for inflammatory conditions that may cause fatigue 1

• Urinalysis

  • Screens for infection, kidney disease, and diabetes 1

• Lipid Profile

  • Assesses for dyslipidemia 1
  • Elevated total cholesterol has been associated with fatigue 4

Additional Testing Based on Clinical Suspicion

For Suspected Anemia

• Iron Studies 1, 2

  • Ferritin and iron levels
  • Total iron-binding capacity (TIBC)
  • Transferrin saturation
  • Particularly important as iron deficiency significantly contributes to fatigue 1, 5

• Vitamin B12 and Folate Levels 2

  • Essential for evaluating macrocytic anemia
  • Deficiencies can cause fatigue even before anemia develops

For Suspected Cardiac Issues

• 12-lead Electrocardiogram 1
• Natriuretic peptides (BNP or NT-proBNP) 1
  • Particularly for patients with dyspnea or exercise intolerance

For Suspected Inflammatory/Autoimmune Conditions

• Autoimmune markers 1
  • Antinuclear antibodies (ANA) have been detected in patients with chronic fatigue 4
• Vitamin D levels 1
  • Particularly in patients with malabsorption conditions

Fatigue Assessment and Stratification

• Use a visual analog scale (0-10) to quantify fatigue severity 3, 1
  • Scores 0-3: Mild fatigue (requires no further assessment)
  • Scores 4-10: Moderate to severe fatigue (requires more focused evaluation)
  • Scores ≥7: Associated with marked decrease in physical functioning 3

Clinical Considerations and Pitfalls

• Normal laboratory values do not exclude fatigue-causing conditions 1

  • Consider expanded testing when symptoms persist despite normal initial workup

• Consider medication side effects 3, 1

  • Review prescription and over-the-counter medications that may contribute to fatigue

• Assess for sleep disturbances 3, 1

  • Sleep disorders are common contributors to fatigue

• Evaluate for emotional distress 3, 1

  • Depression and anxiety can cause or exacerbate fatigue

• Beware of multifactorial causes

  • Fatigue often results from a combination of physical and psychological factors 6
  • Laboratory tests may identify only one component of a complex clinical picture

• Consider specialized testing for persistent unexplained fatigue

  • Bone marrow examination may occasionally be required for diagnosis 7
  • Molecular testing is increasingly used in complex cases 7

Following this systematic laboratory approach will help identify treatable causes of fatigue, improving patient morbidity, mortality, and quality of life.