Comprehensive Laboratory Workup for Fatigue
A comprehensive fatigue workup should include complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, fasting blood glucose, lipid profile, liver function tests, and thyroid-stimulating hormone as core laboratory tests. 1
Initial Assessment and Quantification
- Use a 0-10 numeric rating scale to quantify fatigue severity (mild: 1-3, moderate: 4-6, severe: 7-10) 2
- For moderate to severe fatigue (score ≥4), proceed with more extensive laboratory evaluation 2, 1
- Assess for concurrent symptoms that commonly cluster with fatigue, including pain, emotional distress, and sleep disturbance 2
Core Laboratory Tests for All Patients with Fatigue
- Complete blood count (CBC) with red cell indices such as red cell distribution width (RDW) and mean corpuscular volume (MCV) to assess for anemia, infection, or hematologic disorders 2, 1
- Reticulocyte count to evaluate bone marrow response 2
- Differential blood cell count to identify potential infections or inflammatory conditions 2
- Serum ferritin and transferrin saturation (TfS) to assess iron status 2
- C-reactive protein (CRP) to evaluate inflammation 2, 1
- Urinalysis to screen for renal disease or infection 1
- Serum electrolytes including calcium and magnesium to identify electrolyte imbalances 1
- Blood urea nitrogen (BUN) and serum creatinine to evaluate kidney function 1
- Fasting blood glucose or HbA1c to screen for diabetes 1
- Lipid profile to assess cardiovascular risk 1
- Liver function tests to evaluate hepatic disorders 1
- Thyroid-stimulating hormone (TSH) to screen for thyroid dysfunction 1, 3
Extended Laboratory Evaluation for Moderate to Severe Fatigue
- Vitamin B12 and folic acid levels to identify deficiencies 2
- Haptoglobin, lactate dehydrogenase (LDH), and bilirubin to assess for hemolysis 2
- Percentage of hypochromic red cells and reticulocyte hemoglobin to further evaluate iron status 2
- Soluble transferrin receptor for more accurate assessment of iron deficiency in inflammatory states 2
Disease-Specific Considerations
- For patients with inflammatory bowel disease, evaluate for iron deficiency anemia and anemia of chronic disease 2
- For cancer patients, assess disease status and perform comprehensive evaluation of contributing factors 2
- For patients with suspected heart failure, consider B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1
Important Considerations and Pitfalls
- Laboratory results affect management in only about 5% of fatigue cases, but are essential to rule out treatable causes 1, 4
- If initial laboratory results are normal, repeat testing is generally not indicated unless clinical status changes 4
- Fatigue often coexists with other symptoms, so a multisymptom screening approach is valuable 2
- Consider consulting a hematologist if the cause of anemia remains unclear after extensive workup 2
- Be aware of potential laboratory artifacts in thyroid function tests that may lead to confusing results 5
- Remember that fatigue may be the sole symptom of an underlying disease or one among many symptoms 6
Follow-up Recommendations
- Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 4
- Re-evaluate fatigue severity after addressing any treatable contributing factors identified in laboratory testing 2, 1
- Consider additional specialized testing if initial workup is unrevealing but symptoms persist 1