Laboratory Tests for Diagnosing Causes of Weakness and Fatigue
A comprehensive laboratory workup for patients presenting with weakness and fatigue should include complete blood count, urinalysis, serum electrolytes, kidney and liver function tests, blood glucose, lipid profile, and thyroid-stimulating hormone as core tests to identify treatable causes. 1, 2
Initial Assessment and Quantification
- Quantify fatigue severity using a 0-10 numeric rating scale (mild: 1-3, moderate: 4-6, severe: 7-10) to determine the extent of further evaluation needed 3
- For patients with moderate to severe fatigue (score ≥4), proceed with more extensive laboratory evaluation 3
- Assess for concurrent symptoms that commonly cluster with fatigue, including pain, emotional distress, and sleep disturbance 3
Core Laboratory Tests for All Patients
- Complete blood count (CBC) with red cell indices to assess for anemia, infection, or hematologic disorders 1, 2
- Urinalysis to screen for renal disease or infection 1, 2
- Serum electrolytes including calcium and magnesium to identify electrolyte imbalances 1, 2
- Blood urea nitrogen (BUN) and serum creatinine to evaluate kidney function 1, 2
- Fasting blood glucose or HbA1c to screen for diabetes 1, 2
- Lipid profile to assess cardiovascular risk 1, 2
- Liver function tests to evaluate hepatic disorders 1, 2
- Thyroid-stimulating hormone (TSH) to screen for thyroid dysfunction 1, 2, 4
- C-reactive protein (CRP) to evaluate inflammation 1, 3
Extended Laboratory Evaluation for Moderate to Severe Fatigue
- Ferritin and transferrin saturation to assess iron status 1, 3
- Vitamin B12 and folate levels to identify deficiencies 1, 3
- Reticulocyte count to evaluate bone marrow response 1, 3
- Haptoglobin, lactate dehydrogenase (LDH), and bilirubin to assess for hemolysis when anemia is present 1, 3
- Percentage of hypochromic red cells and reticulocyte hemoglobin for further evaluation of iron status 1, 3
Disease-Specific Considerations
- For patients with inflammatory bowel disease, evaluate for iron deficiency anemia and anemia of chronic disease 3
- For cancer patients or survivors, assess disease status and perform comprehensive evaluation of contributing factors 3
- For patients with suspected heart failure, consider B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1, 2
- For patients with suspected thyroid disease, monitor serum free-T4 levels in addition to TSH 4
Important Considerations and Pitfalls
- Laboratory results affect management in only about 5% of fatigue cases, but are essential to rule out treatable causes 1, 5
- Avoid excessive repeat testing if initial results are normal and symptoms persist without change 5
- Consider rare but serious causes like mitochondrial myopathies in patients with persistent unexplained fatigue, especially with family history 6
- Be aware that biotin supplementation may interfere with thyroid function tests, requiring discontinuation at least 2 days before testing 4
- Recognize that fatigue often coexists with other conditions like fibromyalgia, irritable bowel syndrome, and chronic pain syndromes 7
Follow-up Recommendations
- Re-evaluate fatigue severity after addressing any treatable contributing factors identified in laboratory testing 3, 1
- For patients with normal initial laboratory results but persistent symptoms, consider referral to appropriate specialists based on predominant symptoms 5
- Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 5