Workup for Fatigue
The appropriate workup for fatigue should begin with quantifying its severity on a 0-10 scale, followed by a focused history, physical examination, and targeted laboratory testing based on clinical suspicion, with treatment directed at identified underlying causes. 1
Initial Assessment
Fatigue Screening and Severity Assessment
- Use a numeric rating scale (0-10) where:
- 0 = no fatigue
- 1-3 = mild fatigue (requires education only)
- 4-6 = moderate fatigue (requires evaluation)
- 7-10 = severe fatigue (requires prompt evaluation) 1
- Alternatively, categorize as none, mild, moderate, or severe
For Moderate to Severe Fatigue (Score ≥4)
Focused History
- Onset, pattern, duration, and change over time
- Associated or alleviating factors
- Interference with daily function and activities
- Patient's self-assessment of potential causes 1
- Medication review (prescription, OTC, supplements)
- Review of systems to identify organ systems affected 1
Physical Examination
- Directed by history and review of systems
- Focus on cardiopulmonary, neurologic, and skin examinations 2
- Assess for signs of underlying disease
Evaluation of Common Contributing Factors
Medical Conditions to Assess
- Pain
- Anemia
- Cardiac disease
- Hypothyroidism
- Sleep disorders (disturbance, poor sleep hygiene)
- Nutritional deficiencies
- Underlying malignancy (if suspected based on other symptoms)
- Comorbidities 1
Psychosocial Factors to Assess
- Emotional distress (depression, anxiety)
- Alcohol/substance abuse
- Activity level (excessive or insufficient)
- Social support and caregiver availability 1
Laboratory and Diagnostic Testing
First-Line Testing (Based on Clinical Suspicion)
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests
- Inflammatory markers (ESR, CRP) if indicated
- Additional testing only if directed by history and physical findings 3, 4
Important Caveat
Laboratory studies affect management in only about 5% of patients with fatigue. If initial results are normal, repeat testing is generally not indicated unless new symptoms develop 5.
Management Approach
Treatment of Contributing Factors
- Address identified medical conditions (anemia, hypothyroidism, etc.)
- Manage pain, emotional distress, and sleep disturbances
- Review and modify medications with sedating side effects 1
Non-Pharmacologic Interventions
- Structured physical activity plan with stretching and aerobic exercise (e.g., walking)
- Note: For suspected ME/CFS, exercise may worsen symptoms due to post-exertional malaise 2
- Education and counseling about fatigue patterns and energy conservation
- Cognitive behavioral therapy for chronic fatigue 5
Pharmacologic Considerations
- Selective serotonin reuptake inhibitors if depression is present
- Caffeine or modafinil for episodic situations requiring alertness 5
- Treat specific underlying conditions with appropriate medications
Follow-Up and Monitoring
- Schedule regular follow-up visits rather than sporadic urgent appointments 5
- Continue to monitor for fatigue throughout and after treatment
- Reassess severity and impact on function at each visit
- Adjust management plan based on response to interventions
Common Pitfalls to Avoid
- Excessive laboratory testing when initial results are normal
- Failure to consider common causes (sleep disorders, depression, medication side effects)
- Attributing fatigue to serious illness without supporting evidence
- Overlooking the impact of lifestyle factors on fatigue
- Recommending exercise for patients with ME/CFS without considering post-exertional malaise 2
Remember that while serious underlying conditions are possible causes of fatigue, they are relatively uncommon. Previously undiagnosed cancer accounts for only 0.6% of fatigue cases, and other organic causes represent only about 4.3% 4. A systematic approach focusing on common causes will identify most treatable conditions while avoiding unnecessary testing.