From the Guidelines
A comprehensive diagnostic approach for fatigue should include a thorough history, physical examination, and targeted laboratory tests, starting with a focused fatigue history, including onset, pattern, duration, and associated or alleviating factors, as recommended by the most recent guidelines 1.
Key Components of the Diagnostic Approach
- Perform a focused fatigue history, including:
- Onset, pattern, and duration
- Change over time
- Associated or alleviating factors
- Evaluate disease status by:
- Evaluating risk of recurrence based on stage, pathologic factors, and treatment history
- Performing a review of systems to determine if other symptoms substantiate suspicion for recurrence
- Assess treatable contributing factors, including:
- Comorbidities (e.g., cardiac dysfunction, endocrine dysfunction, pulmonary dysfunction, renal dysfunction, anemia, arthritis, neuromuscular complications, sleep disturbances, pain, emotional distress)
- Medications (consider persistent use of sleep aids, pain medications, or antiemetics)
- Alcohol/substance abuse
- Nutritional issues (including weight/caloric intake changes)
- Deconditioning
Laboratory Tests
- Complete blood count (CBC) to check for anemia or infection
- Thyroid function tests (TSH, free T4) to rule out thyroid disorders
- Basic metabolic panel to assess electrolyte imbalances and kidney function
- Liver function tests to evaluate liver health
- Vitamin B12 and folate levels to check for deficiencies
- Ferritin to assess iron stores
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to screen for inflammation
Additional Tests Based on Clinical Suspicion
- HbA1c for diabetes screening
- Cortisol levels for adrenal function
- Sleep study if sleep apnea is suspected
- Epstein-Barr virus antibodies if mononucleosis is a concern
Considerations for Referral to a Specialist
If all initial tests are normal and symptoms persist, consider referral to a specialist for further evaluation of conditions like chronic fatigue syndrome or fibromyalgia, as recommended by the guidelines 1.
From the Research
Diagnostic Approach for Fatigue
The diagnostic approach for fatigue involves a comprehensive history and physical examination to guide the workup and diagnosis 2. The history and physical examination should focus on identifying common secondary causes, such as medications, anemia, and pregnancy, as well as life-threatening problems like cancer 3.
Classification of Fatigue
Fatigue can be classified as:
- Physiologic fatigue, which can be addressed by proper sleep hygiene, a healthy diet, and balancing energy expenditure 2
- Secondary fatigue, which is improved by treating the underlying condition 2
- Chronic fatigue, which may require cognitive behavior therapy, exercise therapy, and acupuncture 2
Laboratory Investigations
Laboratory investigations have a low yield in discovering treatable physical disorders, with only 5% of patients having their fatigue elucidated by laboratory investigations 3, 4. Minor laboratory abnormalities are common but do not contribute to the diagnostic process and do not seem to influence the clinical outcome 4.
Diagnostic Criteria
The 2015 National Academy of Medicine diagnostic criteria can be used to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) 2. For clinical purposes, only three elements are required: recognition of the typical fatigue, history and physical examination to exclude other medical or psychiatric conditions, and a restricted set of laboratory investigations 5.
Treatment
Treatment of fatigue should include a structured plan for regular physical activity, such as walking, and may involve caffeine, modafinil, and selective serotonin reuptake inhibitors for episodic situations requiring alertness or depression 3. Patients with chronic fatigue may respond to cognitive behavior therapy, and scheduling regular follow-up visits is recommended for effective long-term management 3, 2.