How should I evaluate a patient presenting with fatigue?

Assessment of Fatigue

Begin by screening every patient with a 0-10 numeric rating scale asking "How would you rate your fatigue over the past 7 days?" where scores of 4-10 trigger a comprehensive evaluation for treatable causes. 1

Initial Screening and Severity Stratification

• Use the 0-10 numeric scale where 0 = no fatigue and 10 = worst fatigue imaginable 1

  • Mild fatigue (1-3): Provide education on fatigue management and rescreen at regular intervals 1, 2
  • Moderate fatigue (4-6): Proceed to comprehensive assessment 1
  • Severe fatigue (7-10): Proceed to comprehensive assessment; note that physical functioning drops dramatically at level 7 or higher 1, 2

• Alternatively, use categorical ratings (none, mild, moderate, severe) if numeric scales are impractical 1

• Screen inpatients daily and outpatients at every routine visit, including cancer survivors who have completed treatment 1

Comprehensive Evaluation for Moderate-to-Severe Fatigue (Score 4-10)

Focused Fatigue History

Obtain detailed characterization including: 1, 2

• Onset, pattern, and duration of fatigue 1
• Change over time and temporal relationship to any treatments 1, 2
• Associated or alleviating factors 1
• Impact on daily functioning and enjoyable activities 1
• Patient's self-assessment of perceived causes 1

Critical Red Flags Requiring Urgent Evaluation

Immediately investigate for serious underlying disease if any of these are present: 2

• Fever, drenching night sweats, or unexplained weight loss 2
• New or worsening pain, pulmonary complaints 1, 2
• Lymphadenopathy or hepatosplenomegaly 2
• Moderate-to-severe fatigue emerging or worsening 6-12 months after cancer treatment completion 1, 2

Assessment of Treatable Contributing Factors

Systematically evaluate these nine key domains: 1

1. Medical Comorbidities

• Cardiac dysfunction: especially in patients with history of cardiotoxic therapy or mediastinal radiation 1, 2
• Endocrine dysfunction: hypothyroidism occurs in ~50% of patients after neck/thoracic radiation, typically 5-10 years post-treatment 2
• Pulmonary dysfunction and respiratory compromise 1, 2
• Renal dysfunction affecting metabolic balance 1, 2
• Anemia: compare current hemoglobin/hematocrit with baseline values 1, 2
• Arthritis and neuromuscular complications 1, 2

2. Pain

• Pain frequently clusters with fatigue; effective pain control is essential 1, 2

3. Emotional Distress

• Depression is present in 25-33% of fatigued patients and must be identified 1, 2
• Anxiety also commonly co-occurs 1, 2
• Note that fatigue and depression are independent conditions with different temporal patterns 1

4. Sleep Disturbances

• Affects 30-75% of fatigued patients 1, 2
• Screen for sleep apnea, insomnia, and poor sleep hygiene 2
• Assess for hypersomnia versus insomnia patterns 1

5. Medications

• Review all prescriptions, over-the-counter medications, and supplements 1, 2
• Consider persistent use of sleep aids, pain medications, antiemetics, β-blockers, SSRIs, narcotics, and antihistamines 1, 2
• Deprescribe when possible 2

6. Alcohol/Substance Abuse

• Can aggravate sleep problems and fatigue 1, 2

7. Nutritional Issues

• Weight/caloric intake changes 1
• Vitamin B12, folate, and vitamin D deficiencies 2

8. Activity Level and Deconditioning

• Decreased functional status and reduced activity amplify fatigue 1, 2

9. Disease Status (in cancer patients/survivors)

• Evaluate risk of recurrence based on stage, pathologic factors, and treatment history 1
• Perform review of systems to determine if symptoms suggest recurrence 1
• Informing patients when fatigue is NOT related to recurrence markedly reduces anxiety 1, 2

Physical Examination

Conduct a targeted examination including: 2

• Vital signs with blood pressure assessment 2
• Lymph node palpation 2
• Abdominal examination for hepatosplenomegaly 2
• Cardiovascular evaluation (especially in those with prior radiation/anthracyclines) 2
• Thyroid examination (post-neck/thoracic radiation) 2
• Focused neurological exam when indicated 2

Laboratory Evaluation

For moderate-to-severe fatigue (score 4-10), consider the following based on clinical context: 1

• CBC with differential: compare current hemoglobin/hematocrit to baseline; assess all cell lines (WBC, platelets) 1, 2
• Comprehensive metabolic panel: assess electrolytes, hepatic and renal function 1, 2
• TSH (and free T4): essential because hypothyroidism is highly treatable 1, 2
• ESR and CRP for inflammatory processes 2
• Targeted testing based on clinical suspicion: vitamin B12, folate, vitamin D levels 2
• Echocardiogram for patients with prior cardiotoxic therapy 2

Important caveat: Laboratory studies affect management in only 5% of patients with chronic fatigue, and if initial results are normal, repeat testing is generally not indicated 3, 4. Physical examination produces diagnostic information in only 2% of patients with chronic fatigue 4. Therefore, avoid extensive laboratory testing in the absence of specific clinical indicators 3, 4.

Specialist Referral

Refer to appropriately trained professionals when: 1

• Organ-specific dysfunction is identified (cardiologist, endocrinologist) 1, 2
• Mental health concerns require specialized management 1, 2
• Fatigue persists despite addressing modifiable factors 2
• Use shared decision-making principles for referral decisions 2

Follow-Up Strategy

• Schedule regular follow-up visits rather than sporadic urgent appointments 3
• Rescreen fatigue severity at least annually using the numeric rating scale 1, 2
• Monitor symptom trajectory and response to interventions over time 2

Critical Pitfalls to Avoid

• Do not attribute all symptoms to "fatigue" without evaluating for treatable medical conditions, especially in cancer survivors 2
• Hypothyroidism is common (~50% after thoracic radiation) and often overlooked 2
• Always review medication side effects as potential contributors 2
• Remember that fatigue rarely occurs in isolation; it frequently clusters with pain, sleep disturbance, and emotional distress 1, 2
• Address concerns about disease recurrence promptly, as informing patients when fatigue is unrelated to recurrence markedly reduces anxiety 1, 2