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

Workup for Fatigue

For patients presenting with fatigue, begin by quantifying severity using a 0-10 numeric rating scale: scores of 0-3 require only education and periodic rescreening, while scores of 4-10 mandate a focused evaluation targeting treatable contributing factors with specific laboratory testing. 1

Initial Screening and Severity Assessment

• Screen all patients using a 0-10 numeric scale where 0 = no fatigue and 10 = worst fatigue imaginable, asking specifically about the past 7 days 1, 2
• Mild fatigue (scores 0-3) requires no further workup—provide education on fatigue management and rescreen at regular intervals 3, 2
• Moderate to severe fatigue (scores 4-10) triggers a comprehensive focused evaluation 1, 2
• Recognize that scores ≥7 typically indicate marked decrease in physical functioning and warrant urgent attention 1, 2

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

Fatigue Characteristics

• Document onset, pattern, duration, and temporal changes in fatigue over time 1, 2
• Identify associated or alleviating factors and interference with normal daily activities 1, 2
• Assess the patient's self-assessment of potential causes 1

Red Flag Symptoms Requiring Immediate Attention

• Screen for fever, drenching night sweats, unexplained weight loss, pain, pulmonary complaints, lymphadenopathy, hepatosplenomegaly, or skin manifestations 1
• The presence of these symptoms warrants more extensive workup to screen for metastatic disease or serious comorbidities 3

Medication Review

• Document ALL prescription medications, over-the-counter drugs, herbal supplements, and vitamins 1
• Specifically identify fatigue-inducing agents: β-blockers, SSRIs, narcotics, antidepressants, antiemetics, antihistamines, and sleep aids 1, 4
• Note recent medication changes that temporally correlate with symptom onset 1
• Consider dose adjustments or discontinuation when appropriate 1

Contributing Factors Assessment

• Screen for depression and anxiety using validated tools (PHQ-9 or GAD-7)—present in 25-33% of fatigued patients 1
• Evaluate sleep quality, quantity, hygiene behaviors, and screen time before bed—sleep disturbances occur in 30-75% of fatigued patients 1
• Assess pain severity and characteristics, as pain commonly clusters with fatigue 1, 2
• Screen for alcohol and substance abuse 1
• Document weight changes, current weight, BMI, caloric intake changes, and impediments to nutritional intake 1
• Query functional status, including changes in exercise or activity patterns and ability to accomplish normal daily activities 1

Laboratory Workup for Moderate to Severe Fatigue (Scores 4-10)

The American College of Physicians recommends the following initial screening tests: 1

• Complete blood count with differential (screen for anemia) 1
• Comprehensive metabolic panel (evaluate electrolytes, hepatic, and renal function) 1
• Thyroid-stimulating hormone (TSH) (detect hypothyroidism) 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (assess for inflammation) 1

Additional Testing Based on Clinical Context

• Nutritional assessment if dietary deficiencies suspected 1, 4
• Infectious disease screening for new immigrants or recent travelers (malaria, tuberculosis, schistosomiasis, dengue) 1
• Cardiac evaluation (ECG, echocardiogram) for patients with cardiac risk factors or those who received cardiotoxic treatments 3, 1
• Thyroid screening for patients who received radiation to neck or thorax 3
• Consider disease recurrence or late treatment effects in cancer survivors 1

When to Avoid Extensive Testing

• Imaging studies (chest X-ray, CT, PET/CT) should only be pursued if red flags are present 4
• Mild to moderate fatigue persisting 6-12 months after completion of therapy does not warrant extensive workup unless other symptoms are present 3

Management Approach

Non-Pharmacologic Interventions (Category 1 Recommendations)

• Initiate a structured physical activity program with moderate walking, stretching, and aerobic exercise 2-3 times weekly for 30-60 minutes—this is a Category 1 recommendation 1, 4
• Improve sleep hygiene and implement cognitive behavioral therapy for insomnia if sleep disturbances identified 1, 4
• Provide education and counseling about fatigue patterns and energy-conservation strategies 1
• Offer psychosocial interventions: cognitive-behavioral therapy, psycho-educational therapy, or supportive expressive therapy 1

Treatment of Identified Contributing Factors

• Treat depression or anxiety if present using appropriate pharmacotherapy and/or psychotherapy 1, 4
• Optimize pain management if applicable 1
• Restore nutritional deficiencies with appropriate supplementation 4
• Address identified comorbidities including thyroid dysfunction, cardiac issues, or other medical conditions 1

Specialist Referral Indications

• Refer to cardiology when cardiac evaluation is indicated for persistent fatigue 1
• Refer to endocrine specialists for management of identified endocrine abnormalities 1
• Refer to mental health professionals for refractory depression or anxiety 1
• Consider referral to appropriate specialists if fatigue persists despite addressing contributing factors 1

Follow-Up and Monitoring

• Rescreen at regular intervals for symptom evolution 1, 4
• Inpatients should be screened daily; outpatients at subsequent routine and follow-up visits 3
• Continue monitoring even after treatment completion, as fatigue symptoms may persist 3
• Watchful waiting with regularly scheduled follow-up is appropriate if diagnosis remains unclear after initial workup 4

Common Pitfalls to Avoid

• Do not overlook medication side effects as potential contributors to fatigue—this is commonly missed 1, 2
• Recognize that fatigue rarely occurs in isolation and often clusters with other symptoms 2
• Do not pursue extensive imaging or testing in the absence of red flag symptoms 4
• Avoid dismissing persistent fatigue in cancer survivors without considering disease recurrence 1