What is the best initial workup for a 47-year-old female presenting with fatigue?

Initial Workup for a 47-Year-Old Female with Fatigue

Begin by screening fatigue severity using a 0-10 numeric rating scale, and if the score is ≥4, proceed immediately with a targeted evaluation focusing on treatable medical conditions, psychiatric disorders, and contributing factors rather than extensive laboratory testing. 1

Step 1: Severity Assessment

• Ask the patient to rate fatigue on a 0-10 scale over the past 7 days 2, 1
• Scores 0-3 (mild): No further workup needed; rescreen at regular intervals 2
• Scores 4-10 (moderate to severe): Proceed to focused evaluation immediately 2, 1
• Scores ≥7 typically indicate marked functional impairment and decreased physical functioning 3, 2

Step 2: Focused History (For Scores ≥4)

Document specific fatigue characteristics:

• Onset, pattern, duration, and changes over time 2, 1
• Associated or alleviating factors 2
• Interference with daily activities and functional capacity 2

Screen for common treatable contributing factors:

• Pain: Assess severity and location, as pain commonly clusters with fatigue 2
• Emotional distress: Screen specifically for depression and anxiety symptoms 2, 1
• Sleep disturbance: Evaluate sleep quality, quantity, and sleep hygiene practices 2
• Medications: Complete review of all prescription and over-the-counter medications, as side effects are commonly overlooked 2, 4
• Alcohol/substance use: Screen for misuse that may contribute to fatigue 2

Review of systems targeting:

• Thyroid symptoms (weight changes, temperature intolerance, hair loss) 1
• Cardiovascular symptoms (chest pain, dyspnea, palpitations) 1
• Infectious symptoms (fever, night sweats, weight loss) 1

Step 3: Physical Examination

• Assess for lymphadenopathy 1, 4
• Evaluate for hepatosplenomegaly 1, 4
• Examine thyroid for enlargement 1
• Perform cardiopulmonary and neurologic examination 5

Step 4: Initial Laboratory Testing

Minimum targeted battery (not extensive testing):

• Complete blood count with differential 1, 4
• Comprehensive metabolic panel 1, 4
• Thyroid-stimulating hormone (TSH) 1, 4
• Erythrocyte sedimentation rate (ESR) 1, 4
• C-reactive protein (CRP) for inflammation 4

Additional tests only if clinically indicated:

• Free T4 if TSH abnormal 1
• Vitamin B12, folate, and vitamin D levels based on clinical suspicion 1

Important caveat: Laboratory results affect management in only 5% of patients with fatigue, and if initial results are normal, repeat testing is generally not indicated 6. Cancer as a cause of unexplained fatigue is rare, accounting for only 0.6% of cases 7.

Step 5: Imaging Studies

• Only pursue if red flags are present on history or physical examination 1, 4
• Red flags include: unintentional weight loss, persistent fever, night sweats, focal neurologic findings, or abnormal physical examination findings 3
• Do not order routine imaging in the absence of concerning features 1

Step 6: Management of Identified Causes

Treat specific contributing factors:

• Hypothyroidism, anemia, or other identified medical conditions 1
• Depression with selective serotonin reuptake inhibitors if present 1, 6
• Pain management if pain is contributing 2
• Sleep disorders if identified 2

Universal recommendation regardless of cause:

• Initiate a structured physical activity program with stretching and aerobic exercise 2-3 times weekly for 30-60 minutes 4, 6
• This applies to all patients with fatigue, even before a specific cause is identified 4

Common Pitfalls to Avoid

• Avoid excessive laboratory testing in the absence of specific clinical indicators, as this leads to overdiagnosis 7
• Do not overlook medication side effects as a common and reversible cause 2, 4
• Avoid focusing exclusively on somatic causes when depression and sleep disorders are the most common identifiable causes (depression accounts for 18.5% of persistent fatigue) 7
• Do not order imaging studies without red flag symptoms, as previously undiagnosed cancer is rare (0.6%) 7

Follow-Up Strategy

• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 6
• If diagnosis remains unclear after initial workup, watchful waiting with regularly scheduled follow-up is appropriate 7
• Rescreen fatigue severity at each visit to monitor response to interventions 2