What initial laboratory tests should be ordered to evaluate fatigue?

Initial Laboratory Tests for Fatigue Evaluation

The initial laboratory evaluation for patients presenting with fatigue should include complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose, lipid profile, liver function tests, and thyroid-stimulating hormone. 1

Comprehensive Diagnostic Approach

When evaluating a patient with fatigue, a structured approach is essential to identify treatable causes. Laboratory testing is a key component of this evaluation, particularly when fatigue is moderate to severe.

Step 1: Assess Fatigue Severity

First, quantify the fatigue using a validated scale:

• Use a 0-10 numerical rating scale (NRS) where 0 = no fatigue and 10 = worst possible fatigue
• Categorize as mild (1-3), moderate (4-6), or severe (7-10) 1
• Note that physical functioning dramatically decreases at fatigue levels of 7 or higher 1

Step 2: Initial Laboratory Panel

For moderate to severe fatigue (score ≥4), order the following tests:

• Basic tests:
  • Complete blood count (CBC)
  • Urinalysis
  • Comprehensive metabolic panel including:
    • Serum electrolytes (sodium, potassium, chloride, calcium, magnesium)
    • Blood urea nitrogen (BUN)
    • Serum creatinine
    • Liver function tests
  • Fasting blood glucose (or glycohemoglobin)
  • Thyroid-stimulating hormone (TSH)
  • Lipid profile
  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) 1

Step 3: Additional Testing Based on Clinical Suspicion

Consider these additional tests when clinically indicated:

• Iron studies (serum iron, total iron-binding capacity, ferritin) if anemia is present 2
• Vitamin B12 and folate levels if macrocytic anemia is present
• Specific hormone testing (e.g., testosterone) in appropriate clinical contexts 1
• Screening for infectious diseases when suspected (e.g., HIV, hepatitis)

Interpretation and Next Steps

Laboratory results should be interpreted in the context of the patient's clinical presentation:

1. Anemia: If CBC shows abnormalities, classify as microcytic, normocytic, or macrocytic and pursue appropriate additional testing 2

2. Metabolic disorders: Abnormal glucose, electrolytes, renal or liver function may indicate underlying conditions requiring treatment

3. Thyroid dysfunction: Abnormal TSH suggests hypo- or hyperthyroidism as a potential cause of fatigue

4. Inflammatory conditions: Elevated inflammatory markers may indicate underlying inflammatory or autoimmune conditions

Important Considerations and Pitfalls

• Laboratory abnormalities may not explain fatigue: The presence of an abnormal laboratory result does not necessarily indicate the cause of fatigue, especially in chronic cases 3

• Consider psychological factors: In patients with chronic fatigue (>1 year), psychological assessment is particularly important as laboratory abnormalities alone may not guide effective treatment 3

• Assess treatable contributing factors: Always evaluate for pain, emotional distress, sleep disturbance, anemia, nutritional status, activity level, medication side effects, and comorbidities 1

• Avoid over-testing: While laboratory testing is important, excessive testing without clinical indication can lead to unnecessary costs and patient anxiety

• Re-evaluate after treatment: After addressing any identified abnormalities, reassess fatigue levels to determine if interventions have been effective 1

Remember that fatigue is often multifactorial, and laboratory testing is just one component of a comprehensive evaluation that should also include assessment of disease status, medication review, and psychosocial factors.