What is the appropriate workup for an adult patient with no significant medical history presenting with fatigue?

Workup for Fatigue in Adults Without Significant Medical History

For adults presenting with fatigue, begin by quantifying severity using a 0-10 numeric rating scale: scores of 0-3 (mild) require only education and periodic rescreening, while scores of 4-10 (moderate to severe) warrant a focused evaluation with targeted laboratory testing. 1, 2

Initial Severity Assessment

• Use a 0-10 numeric rating scale where 0 = no fatigue and 10 = worst fatigue imaginable 1, 2
• Mild fatigue (scores 0-3): No further workup needed; provide education and rescreen at regular intervals 1, 2
• Moderate to severe fatigue (scores 4-10): Proceed with comprehensive evaluation 1, 2
• Scores ≥7 typically indicate marked functional impairment requiring urgent assessment 1, 3

Focused History for Moderate to Severe Fatigue (Scores 4-10)

Document specific fatigue characteristics:

• Onset, pattern, duration, and temporal changes 4, 1, 2
• Associated or alleviating factors 4, 2
• Interference with daily functioning and activities 2
• Patient's own assessment of potential causes 2

Screen for red flag symptoms:

• Fever, drenching night sweats, unexplained weight loss >10% over 6 months 1, 3
• Unintentional weight loss, pain, pulmonary complaints 1, 3
• Lymphadenopathy, hepatosplenomegaly, skin manifestations 1, 3

Assess treatable contributing factors:

• Pain severity and management 2
• Depression and anxiety (present in 25-33% of fatigued patients) 1, 5
• Sleep quality, quantity, hygiene, and symptoms of sleep apnea (disturbances occur in 30-75% of fatigued patients) 1
• Current medications and potential side effects 4, 2
• Alcohol and substance use 4, 2
• Nutritional status and recent dietary changes 4
• Activity level and deconditioning 4

Laboratory Workup for Moderate to Severe Fatigue

Initial screening tests for all patients with scores 4-10:

• Complete blood count with differential 4, 1, 3
• Comprehensive metabolic panel (electrolytes, hepatic and renal function) 4, 1, 3
• Thyroid-stimulating hormone (TSH) 4, 1, 3
• Erythrocyte sedimentation rate (ESR) 1, 3
• C-reactive protein (CRP) 1, 3

This approach is evidence-based: serious somatic disease is rare (4.3%) in primary care patients with fatigue, and previously undiagnosed cancer accounts for only 0.6% of cases 5, 6. Depression (18.5%) and sleep disorders are far more common causes 5, 6.

Additional testing only if clinically indicated:

• Further endocrinologic evaluation if symptoms suggest thyroid or adrenal dysfunction 4
• HIV testing, malaria screening, tuberculosis testing for new immigrants or recent travelers 1, 3
• Chest X-ray only if pulmonary symptoms or red flags present 3

Management Regardless of Cause

Initiate these interventions for all patients with fatigue:

• Structured physical activity program: 150 minutes of moderate aerobic exercise weekly with 2-3 strength training sessions 4, 1
• Sleep hygiene optimization 1
• Education about fatigue patterns and self-monitoring 4, 2

Address identified contributing factors:

• Treat depression or anxiety if present (consider PHQ-9 or GAD-7 screening) 1
• Implement cognitive behavioral therapy for insomnia if sleep disturbance identified 1
• Optimize pain management if applicable 1, 2
• Correct anemia, thyroid dysfunction, or other identified abnormalities 4, 1

Follow-Up Strategy

• Avoid extensive investigations in the absence of red flags or abnormal initial testing 7, 5, 6
• Consider watchful waiting with regularly scheduled follow-up visits 2, 5
• Rescreen at regular intervals to monitor symptom evolution 1, 2
• Refer to specialists only if fatigue persists despite addressing contributing factors or if specific findings warrant subspecialty evaluation 1

Critical Pitfalls to Avoid

• Do not pursue extensive somatic testing without specific clinical findings, as this leads to overdiagnosis and reinforces illness behavior 5, 6
• Recognize that in approximately 75% of primary care fatigue cases, no specific cause is identified 8
• Avoid overlooking medication side effects as contributors 2
• Remember that fatigue rarely occurs in isolation and often clusters with other symptoms like pain, depression, and sleep disturbance 2
• Do not use psychostimulants or dietary supplements, as they lack efficacy for fatigue management 3