From the Guidelines
The workup for fatigue should begin with a comprehensive history and physical examination to identify potential causes, as recommended by the most recent guidelines from the European Society for Medical Oncology (ESMO) in 2020 1.
Key Components of the Workup
- Perform a focused fatigue history, including onset, pattern, duration, change over time, and associated or alleviating factors, as outlined in the American Society of Clinical Oncology (ASCO) clinical practice guideline adaptation from 2014 1.
- Evaluate disease status by assessing the risk of recurrence based on stage, pathologic factors, and treatment history, and perform a review of systems to determine if other symptoms substantiate suspicion for recurrence.
- Assess treatable contributing factors, including comorbidities, medications, alcohol/substance abuse, nutritional issues, weight/caloric intake changes, and deconditioning.
Laboratory Tests and Screening
- Start with basic laboratory tests, including complete blood count, comprehensive metabolic panel, thyroid function tests, and inflammatory markers like ESR or CRP.
- Additional first-line tests should include urinalysis, fasting blood glucose, and ferritin levels.
- If these are unrevealing, consider screening for sleep disorders, depression, and anxiety using validated questionnaires like the PHQ-9 or GAD-7, as suggested by the NCCN clinical practice guidelines for cancer-related fatigue in 2010 1.
Further Testing and Referral
- Further testing may include vitamin B12, vitamin D levels, and cortisol levels if clinically indicated.
- For persistent unexplained fatigue lasting over six months with post-exertional malaise, consider chronic fatigue syndrome.
- Specific testing should be guided by associated symptoms, such as polysomnography for suspected sleep apnea, or autoimmune panels if joint pain or rashes are present.
- Referral to an appropriately trained professional, such as a cardiologist, endocrinologist, mental health professional, or internist, may be necessary, as stated in the ASCO clinical practice guideline adaptation from 2014 1.
From the Research
Initial Assessment
When approaching a patient with fatigue, it is essential to start with a comprehensive history and examination, as recommended by 2. This initial assessment helps identify potential underlying causes and guides further investigation.
Laboratory Tests
Laboratory tests, such as a Complete Blood Count (CBC), can be useful in assessing cardiovascular and metabolic diseases, which may be contributing to fatigue 3. The CBC components, including white blood cell count, neutrophil-to-lymphocyte ratio, hemoglobin, and others, can help predict the risk of certain diseases.
- Key components of a CBC that may be relevant to fatigue include:
- White blood cell count
- Neutrophil-to-lymphocyte ratio
- Hemoglobin
- Mean corpuscular volume
- Red cell distribution width
- Platelet count
- Mean platelet volume
- Platelet-to-lymphocyte ratio
Basic Metabolic Panel
A basic metabolic panel can also provide valuable information about a patient's electrolyte balance, renal function, and acid-base homeostasis, all of which can impact fatigue 4. The panel includes measurements of:
- Potassium
- Chloride
- Blood urea nitrogen
- Creatinine
Approach to Investigation
Based on the current literature, a rational approach to investigating fatigue involves:
- A comprehensive history and examination
- Consideration of a period of watchful waiting in the absence of red flags
- Judicious use of tests, such as CBC and basic metabolic panel, once the decision to investigate is made 2