Diagnostic Testing for Fatigue
All patients presenting with fatigue should be screened using a 0-10 numeric rating scale, and those scoring ≥4 (moderate to severe) require focused laboratory testing including CBC with differential, comprehensive metabolic panel, and TSH. 1
Initial Screening Approach
- Use a 0-10 numeric rating scale where 1-3 indicates mild fatigue, 4-6 moderate, and 7-10 severe fatigue 1
- Screen at diagnosis, at regular intervals during treatment, and at least annually in all patients 1
- Patients scoring ≥4 require comprehensive diagnostic assessment 1
Focused Fatigue History (for moderate to severe fatigue)
When fatigue scores ≥4, obtain specific details about:
- Onset, pattern, and duration of symptoms 1
- Changes over time and temporal relationships 1
- Alleviating and aggravating factors 1
- Impact on daily functioning and quality of life 2
Laboratory Testing Battery
The following tests should be performed based on severity and clinical presentation:
Essential Laboratory Tests
- Complete blood count with differential to assess for anemia and compare with baseline hemoglobin/hematocrit values 1, 2
- Comprehensive metabolic panel to evaluate electrolytes, hepatic function, and renal function 1, 2
- Thyroid-stimulating hormone (TSH) to screen for hypothyroidism 1, 2
Additional Considerations
- Erythrocyte sedimentation rate or C-reactive protein for systemic inflammation 2
- Vitamin D, iron studies, and B12 levels may be considered 2
- Further testing should be guided by specific symptoms and clinical suspicion rather than routine screening 3
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 3
Assessment of Contributing Factors
Systematically evaluate these treatable conditions:
Medical Comorbidities
- Cardiac dysfunction (especially in patients who received cardiotoxic treatments) 1
- Endocrine dysfunction beyond thyroid (consider comprehensive evaluation if other symptoms present) 1
- Pulmonary dysfunction 1
- Renal dysfunction 1
- Anemia 1
- Neuromuscular complications 1
Psychosocial Factors
- Sleep disturbances (present in 30-75% of chronic fatigue cases) 1, 2
- Emotional distress, anxiety, and depression using validated screening tools 1, 2
- Consider the two-question depression screen: "In the last month, have you felt dejected, sad, depressed or hopeless?" and "Did you experience significantly less pleasure than usual?" 1
- Pain 1
Lifestyle and Medications
- Medication review (particularly sleep aids, pain medications, antiemetics, and sedating drugs) 1, 2
- Alcohol or substance use 1, 2
- Nutritional status and weight changes 1, 2
- Activity level and deconditioning 1, 2
Disease Status Evaluation
- Evaluate risk of recurrence based on stage, pathologic factors, and treatment history 1
- Perform review of systems to determine if symptoms suggest disease recurrence 1
- More extensive workup is warranted when moderate to severe fatigue begins after or worsens 6-12 months post-treatment, or when accompanied by pain, pulmonary complaints, or unintentional weight loss 1
When to Refer
Referral to specialists should be considered when:
- Specific organ dysfunction is identified requiring specialist management (cardiology, endocrinology, mental health) 1, 2
- Fatigue persists despite addressing treatable factors 2
- Complex psychiatric comorbidity is present 1
Common Pitfalls
- Avoid extensive "fishing expeditions" with laboratory testing when history and physical examination do not suggest specific pathology 3, 4
- Do not assume fatigue will resolve after treating identifiable factors—it may persist and require ongoing management 2
- Do not overlook lifestyle factors including physical activity, sleep hygiene, and stress management 2
- Recognize that psychiatric illness (depression, anxiety) is not a diagnosis of exclusion but should be suspected based on history 4