Laboratory Workup for Fatigue in Adults
For an adult with no significant medical history presenting with fatigue, order a complete blood count with differential, comprehensive metabolic panel (including electrolytes, renal and hepatic function), and thyroid-stimulating hormone (TSH) as your core laboratory evaluation. 1, 2
Initial Severity Assessment
Before ordering labs, quantify the fatigue severity using a 0-10 numeric rating scale (0 = no fatigue, 10 = worst imaginable). 1
- Mild fatigue (1-3): No immediate lab workup needed; provide education and rescreen periodically 1
- Moderate to severe fatigue (4-10): Proceed with comprehensive assessment and laboratory evaluation 1
Core Laboratory Panel
The following tests should be considered based on symptom severity, onset timing, and presence of other symptoms: 1
Essential Tests:
- Complete blood count (CBC) with differential: Evaluate for anemia (compare current hemoglobin/hematocrit to any baseline values), assess white blood cell and platelet counts 1, 2
- Comprehensive metabolic panel: Check electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, and assess hepatic function 1, 2
- Thyroid-stimulating hormone (TSH): Screen for hypothyroidism 1, 2
Additional First-Line Tests:
- Fasting blood glucose or HbA1c: Evaluate for diabetes 1, 2
- Urinalysis: Part of comprehensive initial evaluation 1, 2
Context-Dependent Laboratory Additions
If cardiac symptoms are present (dyspnea, chest discomfort, orthopnea), add B-type natriuretic peptide (BNP) or NT-proBNP to evaluate for heart failure. 2
If more comprehensive endocrine evaluation is warranted based on clinical presentation (weight changes, temperature intolerance, menstrual irregularities), consider referral to endocrinology for expanded testing beyond TSH. 1
Important Clinical Caveats
Low Yield of Extensive Testing
Research demonstrates that physical examination findings contribute diagnostically in only 2% of chronic fatigue cases, and laboratory investigations identify the cause in only 5% of patients. 3 Minor laboratory abnormalities are common but often do not contribute to diagnosis or influence clinical outcome. 3, 4
When to Expand the Workup
Order additional labs if: 1
- Other concerning symptoms are present (unintentional weight loss, pain, pulmonary complaints) 1
- Fatigue worsens significantly after an initial period of stability 1
- Fatigue is severe (7-10 on numeric scale) 1, 2
What NOT to Order Routinely
Avoid ordering extensive autoimmune panels, viral serologies, or other specialized tests without specific clinical indicators, as these have extremely low diagnostic yield in undifferentiated fatigue. 3, 4
Beyond Laboratory Testing
Always assess for treatable contributing factors: 1
- Medications (sleep aids, pain medications, antiemetics, over-the-counter supplements) 1, 2
- Sleep disturbances 1
- Pain 1, 2
- Emotional distress, depression, or anxiety 1
- Alcohol or substance use 1
- Nutritional deficits and weight changes 1
- Deconditioning and activity level 1
Psychological factors are often more relevant than laboratory abnormalities in chronic fatigue lasting over one year, with the majority of such patients showing elevated depression and psychological symptom scores. 4