Workup for Excessive Tiredness
The workup for excessive tiredness should begin with screening for fatigue severity using a numeric rating scale (0-10), followed by a focused evaluation for patients with moderate to severe fatigue (scores 4-10), including assessment of treatable contributing factors and appropriate laboratory and imaging studies. 1, 2
Initial Assessment
- Screen all patients using a numeric rating scale (0-10) or categorization as none, mild, moderate, or severe 1
- Patients with scores of 0-3 (mild) require only education and periodic rescreening 1
- Patients with scores of 4-10 (moderate to severe) warrant a more focused evaluation 1
- Patients with scores ≥7 typically experience a marked decrease in physical functioning 1
Focused History and Physical Examination
- Conduct a thorough review of systems to identify affected organ systems 3
- Assess fatigue characteristics: onset, pattern, duration, changes over time 3
- Evaluate associated or alleviating factors 3
- Assess interference with normal functioning and daily activities 3
- Consider patient's self-assessment of potential causes 3
- Document presence of associated symptoms such as fever, night sweats, weight loss, cough, dyspnea 2
Laboratory Studies
- Complete blood count with differential to evaluate for cytopenias, leukocytosis, or abnormal cells 2
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess inflammation 2
- Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, lactate dehydrogenase, and albumin 2
- Thyroid-stimulating hormone (TSH) to rule out thyroid dysfunction 2
- Consider HIV testing and tuberculosis screening (IGRA or TST) based on risk factors 2
Imaging Studies
- Chest X-ray as initial screening for pulmonary pathology 2
- Consider contrast-enhanced CT scan of neck, chest, and abdomen if lymphadenopathy, organomegaly, or malignancy is suspected 2
- Consider PET/CT scan if lymphoma is suspected 2
Assessment of Treatable Contributing Factors
- Pain assessment and management (pain frequently clusters with fatigue) 1
- Screen for depression and anxiety, which commonly co-occur with fatigue 1, 4
- Evaluate sleep quality, quantity, and hygiene 1, 5
- Review medications for potential side effects contributing to fatigue 1
- Screen for alcohol/substance use 1
- Consider sleep disorders such as sleep apnea, narcolepsy, or hypersomnia 6, 5
Disease-Specific Considerations
- For cancer patients or survivors, assess disease status and treatment effects 3
- Consider myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) if fatigue persists >6 months with postexertional malaise 4
- Evaluate for secondary causes including:
Common Pitfalls to Avoid
- Overlooking medication side effects as potential contributors to fatigue 1
- Excessive focus on rare organic causes, leading to overdiagnosis (undiagnosed cancer accounts for only 0.6% of fatigue cases) 7
- Failing to recognize that fatigue rarely occurs in isolation and often clusters with other symptoms 1
- Neglecting to assess sleep disorders, which are among the most common causes of persistent fatigue 7
- Recommending exercise without consideration for postexertional malaise in ME/CFS patients 4
Management Approach
- For physiologic fatigue: improve sleep hygiene, maintain healthy diet, and balance energy expenditure 4
- For secondary fatigue: treat the underlying condition 4
- For chronic fatigue: consider cognitive behavioral therapy, appropriate exercise therapy (except in ME/CFS), and symptom management 4
- If diagnosis remains unclear after initial evaluation, implement watchful waiting with scheduled follow-up to prevent excessive focus on somatic causes 7