What is the recommended history, physical examination, and initial laboratory workup for a patient presenting with fatigue?

Fatigue Workup: Recommended Approach

For patients presenting with fatigue, begin by quantifying severity using a 0-10 numeric rating scale; those scoring 4-10 require a comprehensive evaluation including complete blood count with differential, comprehensive metabolic panel, thyroid-stimulating hormone, erythrocyte sedimentation rate, and C-reactive protein, while those scoring 0-3 need only education and periodic rescreening. 1

Initial Screening and Severity Stratification

• Use a 0-10 numeric rating scale where 0 = no fatigue and 10 = worst fatigue imaginable to quantify severity over the prior 7 days 1, 2
• Mild fatigue (scores 0-3) requires only patient education about fatigue patterns and rescreening at regular intervals 1, 3
• Moderate to severe fatigue (scores 4-10) mandates immediate focused evaluation for treatable contributing factors 1, 2
• Physical functioning declines markedly at scores ≥7, making prompt intervention critical 2

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

Fatigue Characterization

• Document onset, pattern, duration, and temporal changes in fatigue over time 1, 3, 2
• Identify alleviating and aggravating factors 1
• Assess interference with normal daily functioning and the patient's self-assessment of potential causes 1

Red Flag Symptoms Requiring Urgent Evaluation

• Screen for fever, drenching night sweats, or unexplained weight loss, which suggest malignancy or infection 1, 2
• Evaluate for new or worsening pain, pulmonary complaints, and unintentional weight loss 1, 2
• Document presence of lymphadenopathy, hepatosplenomegaly, or concerning skin manifestations 1, 2

Comprehensive Medication Review

• Document all prescription medications, over-the-counter drugs, herbal supplements, and vitamins 1, 3
• Identify recent medication changes that temporally correlate with fatigue onset 1, 3
• Specifically assess for fatigue-inducing agents: β-blockers, SSRIs, narcotics, antidepressants, antiemetics, and antihistamines 1, 2
• Consider dose adjustments or discontinuation when appropriate 1, 2

Assessment of Contributing Symptom Clusters

• Evaluate sleep quality, quantity, and hygiene; sleep disturbances occur in 30-75% of fatigued patients 1, 3, 2
• Screen specifically for sleep apnea, particularly if weight gain or other risk factors are present 1
• Screen for depression using PHQ-9, as depression is present in 25-33% of fatigued patients 1, 2
• Screen for anxiety using GAD-7 1
• Assess pain levels, as pain frequently clusters with fatigue 2
• Evaluate alcohol and substance abuse, which can aggravate sleep disturbance and fatigue 1, 2

Nutritional and Functional Assessment

• Document weight changes, current weight, and calculate body mass index 1
• Evaluate caloric intake changes and impediments to nutritional intake 1
• Query about functional status, including changes in exercise or activity patterns 1, 3
• Determine if patients can accomplish normal daily activities 1, 3

Special Population Considerations

• For new immigrants or recent travelers, assess for tropical diseases including malaria, tuberculosis, schistosomiasis, and dengue 1
• For cancer survivors, consider disease recurrence or late treatment effects 1, 2
• In cancer survivors with prior radiation to neck or thorax, recognize that hypothyroidism occurs in approximately 50% of patients, typically 5-10 years after treatment 2

Physical Examination

Vital Signs and General Assessment

• Obtain vital signs with blood pressure assessment 2
• Document weight and calculate BMI 1

Focused Examination Based on History

• Lymph node palpation to detect lymphadenopathy 1, 2
• Abdominal examination for hepatosplenomegaly 1, 2
• Skin inspection for concerning manifestations 1, 2
• Cardiovascular evaluation, especially in patients with prior cardiotoxic therapy or mediastinal radiation 2
• Thyroid examination, particularly in patients with history of neck or thoracic radiation 2
• Focused neurological examination when indicated by history 2

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

Core Laboratory Tests

• Complete blood count with differential to screen for anemia, infection, or malignancy 1, 3, 2
• Comprehensive metabolic panel to assess electrolytes, hepatic function, and renal function 1, 3, 2
• Thyroid-stimulating hormone (TSH) to detect hypothyroidism 1, 3, 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate for inflammatory processes 1, 3, 2

Additional Testing Based on Clinical Context

• HIV testing and tuberculosis screening if risk factors are present 3
• Vitamin B12, folate, and vitamin D levels if nutritional deficiencies are suspected 2
• Echocardiogram for patients with prior cardiotoxic therapy or cardiac symptoms 2
• Extended endocrine workup when clinically indicated 2

Management of Identified Contributing Factors

Medical Comorbidities

• Treat hypothyroidism, anemia, and cardiac dysfunction when identified 2
• Optimize management of existing comorbidities including cardiac, endocrine, pulmonary, and renal dysfunction 1, 2
• Address pain through effective pain control strategies 2

Medication Optimization

• Taper or discontinue fatigue-inducing medications when appropriate 1, 2
• Consider dose adjustments for essential medications 1

Mental Health and Sleep

• Treat depression and anxiety using validated screening tools and consider SSRIs when appropriate 1, 2
• Implement cognitive-behavioral therapy for insomnia 1, 2
• Treat sleep apnea when present 1, 2

Nutritional and Activity Interventions

• Correct nutritional deficiencies and ensure adequate caloric intake 2
• Implement a structured physical activity program (e.g., moderate walking) as this improves strength, energy, and overall fitness 1, 2
• Provide education about energy conservation strategies 1

Specialist Referral Indications

• Refer to cardiology when cardiac evaluation (ECG, echocardiogram) is indicated for persistent fatigue 1
• Refer to endocrinology for management of identified endocrine abnormalities 1
• Refer to mental health professionals for refractory depression or anxiety 1
• Consider referral to other specialists based on specific clinical findings 1, 2

Follow-Up Strategy

• Reassess fatigue severity at each visit using the numeric rating scale 3, 2
• Schedule regular follow-up visits (at least annually) to monitor symptom trajectory 2
• Continue to monitor for fatigue throughout and after treatment, as symptoms can persist 4

Critical Pitfalls to Avoid

• Do not overlook medication side effects as potential contributors to fatigue; this is a commonly missed cause 1, 3, 2
• Do not attribute all symptoms to "fatigue" without thorough evaluation for treatable medical conditions 2
• Recognize that hypothyroidism is common (approximately 50%) after thoracic radiation and is often overlooked 2
• Remember that fatigue rarely occurs in isolation; it frequently clusters with pain, sleep disturbance, and emotional distress 3, 2
• In cancer survivors, promptly address concerns about disease recurrence, as informing patients when fatigue is not related to recurrence markedly reduces anxiety 2