What is the workup for a patient presenting with extreme fatigue?

Workup for Extreme Fatigue

Begin by quantifying fatigue severity using a 0-10 numeric scale; if the score is ≥4, proceed immediately with a focused evaluation targeting treatable medical conditions and contributing factors rather than extensive laboratory testing. 1

Initial Severity Assessment and Screening

• Ask the patient: "How would you rate your fatigue on a scale of 0 to 10 over the past 7 days?" 2, 1
• Scores of 0-3 (mild) require only patient education about fatigue management strategies and routine rescreening at regular intervals 2, 1
• Scores of 4-6 (moderate) warrant a focused evaluation as outlined below 2, 1
• Scores of ≥7 (severe) indicate marked functional impairment and require immediate comprehensive workup 2, 1, 3
• A worsening pattern over 3 days is particularly concerning and mandates thorough evaluation regardless of the absolute severity score 3

Focused History (For Scores ≥4)

Red Flag Symptoms Assessment

• Screen specifically for unintentional weight loss, pain, pulmonary complaints, or new neurological symptoms—these suggest possible malignancy or serious underlying disease and necessitate imaging studies 3
• Determine the onset, pattern, duration, and change over time of the fatigue 2
• Assess whether fatigue began after or worsened during the 6-12 month period following any prior cancer treatment 2

Medication and Substance Review

• Conduct a complete inventory of all prescription medications, over-the-counter drugs, herbal supplements, and vitamins 3
• Specifically review β-blockers, narcotics, antidepressants, antiemetics, and antihistamines as these commonly cause excessive drowsiness 3
• Assess alcohol and substance use 1

Treatable Contributing Factors

• Evaluate for pain, emotional distress (particularly depression and anxiety), sleep disturbance, poor sleep hygiene, anemia, nutritional deficiencies, and activity level 2, 1
• Depression accounts for 18.5% of persistent fatigue cases 4
• Sleep disorders and sleep-related breathing disorders are among the most common causes 4

Social Support Assessment

• Evaluate the availability of dependable caregivers, as fatigue is a major cause of functional dependence, especially in elderly patients 2

Physical Examination

• Perform a lymph node assessment and evaluate for hepatosplenomegaly 1
• Complete a review of systems to determine which organ systems are affected 2

Laboratory Workup

Initial Screening Tests (For Scores ≥4)

• Complete blood count with differential 1, 3
• Comprehensive metabolic panel 1, 3
• Thyroid-stimulating hormone 1, 3
• Erythrocyte sedimentation rate and C-reactive protein for inflammation 1, 3

Additional Testing

• Order additional tests only based on specific findings from history and physical examination, such as echocardiogram if cardiac symptoms are present 3
• Laboratory results affect management in only 5% of patients, and if initial results are normal, repeat testing is generally not indicated 5

Imaging Studies

• Pursue imaging studies (chest X-ray, CT chest/abdomen/pelvis with contrast, or PET/CT) only if red flags are present 1
• Previously undiagnosed cancer accounts for only 0.6% of fatigue cases, making extensive imaging inappropriate without specific concerning features 4

Treatment Approach

First-Line Non-Pharmacological Interventions

• Implement a structured physical activity program with stretching and aerobic exercise 2-3 times weekly for 30-60 minutes, including both aerobic and resistance training, regardless of the underlying cause 1, 3, 5
• Provide patient and family education about fatigue management 3
• Consider cognitive behavioral therapy and other psychosocial interventions such as behavioral therapy, psychotherapy, support groups, relaxation techniques, energy conservation, and stress management 3

Pharmacological Considerations

• Psychostimulants and dietary supplements are not recommended due to lack of efficacy 1
• Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, or sertraline) may improve energy specifically in patients with documented depression 5

Follow-Up and Monitoring

• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 5
• Continue to monitor for fatigue at all subsequent routine visits, as fatigue symptoms can persist even after treatment of contributing factors 2, 3
• If moderate-to-severe fatigue persists after treating contributing factors, implement non-pharmacological interventions as outlined above 3

Common Pitfalls to Avoid

• Avoid extensive "fishing expedition" laboratory testing when initial screening is normal, as this leads to overdiagnosis 6, 4
• Do not pursue an exclusively somatic focus when the diagnosis remains unclear after initial workup 4
• For patients with mild to moderate fatigue persisting 6-12 months after cancer treatment completion, an extensive workup is not warranted unless other symptoms are present 2