Laboratory Workup for Extreme Fatigue
For patients presenting with extreme fatigue, order a comprehensive initial laboratory panel including: complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose or HbA1c, lipid profile, liver function tests, and thyroid-stimulating hormone. 1
Initial Assessment
Before ordering labs, quantify the fatigue severity using a 0-10 numeric rating scale, where extreme fatigue typically scores 7-10. 1 This severity assessment guides the extent of workup needed and helps track response to interventions.
Core Laboratory Panel
The following tests should be ordered for all patients with extreme fatigue, as recommended by the American Heart Association: 1
- Complete blood count (CBC) - screens for anemia, infection, and hematologic disorders 1
- Urinalysis - evaluates for renal disease or urinary tract infection 1
- Serum electrolytes (including calcium and magnesium) - identifies metabolic imbalances that commonly cause fatigue 1
- Blood urea nitrogen (BUN) and serum creatinine - assesses kidney function 1
- Fasting blood glucose or HbA1c - screens for diabetes, a common cause of fatigue 1
- Lipid profile - evaluates cardiovascular risk factors 1
- Liver function tests - detects hepatic disorders 1
- Thyroid-stimulating hormone (TSH) - screens for hypothyroidism, one of the most common treatable causes of fatigue 1
Clinical Context Matters
Important caveat: Laboratory results affect management in only 5% of patients with fatigue, and if initial results are normal, repeat testing is generally not indicated. 2 This underscores the importance of a thorough clinical evaluation alongside laboratory testing.
The workup should be tailored based on specific clinical scenarios:
For cancer patients or survivors: Evaluate disease status and assess for contributing factors like emotional distress, sleep disturbance, pain, and medication effects. 3 Consider more extensive workup if fatigue worsens after treatment completion or is accompanied by pain, pulmonary complaints, or unintentional weight loss. 3
For suspected heart failure: Add B-type natriuretic peptide (BNP) or NT-proBNP to the workup. 1
For patients with cardiotoxic treatment history: Consider echocardiogram in addition to labs. 3
What NOT to Do
Avoid over-testing. Previously undiagnosed cancer accounts for only 0.6% of fatigue cases, and anemia or other organic causes represent only 4.3% of cases. 4 Depression (18.5%), sleep disorders, and psychosocial stress are far more common culprits. 4 An exclusively somatic focus leads to overdiagnosis and unnecessary testing. 4
Do not order investigations beyond the basic panel unless additional symptoms or abnormal findings are present. 4 If the diagnosis remains unclear after initial workup, watchful waiting with regularly scheduled follow-up is more appropriate than extensive additional testing. 4
Additional Evaluation Beyond Labs
Regardless of laboratory results, screen for: 3
- Emotional distress and depression
- Sleep disturbances
- Pain
- Prescription and over-the-counter medications that may cause fatigue
- Cardiac disease through history and physical examination