From the Guidelines
For a lab workup to evaluate fatigue, I recommend starting with a complete blood count (CBC), comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), and ferritin level, as these tests can identify common causes of fatigue including anemia, electrolyte abnormalities, kidney or liver dysfunction, thyroid disorders, and iron deficiency, as suggested by the most recent and highest quality study 1.
Initial Evaluation
The initial evaluation of fatigue should include a thorough medical history, physical examination, and laboratory tests to identify potential underlying causes. The laboratory tests should include:
- Complete blood count (CBC) with differential to evaluate for anemia, infection, or blood disorders
- Comprehensive metabolic panel (CMP) to assess electrolyte levels, kidney function, and liver function
- Thyroid-stimulating hormone (TSH) to evaluate for thyroid disorders
- Ferritin level to assess for iron deficiency
Additional Tests
Additional tests may be considered based on the patient's symptoms, medical history, and physical examination findings. These may include:
- Hemoglobin A1c to screen for diabetes
- Vitamin B12 and folate levels to check for deficiencies
- Vitamin D level to assess for deficiency
- Inflammatory markers such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) to evaluate for inflammatory causes
- Screening for infectious causes such as mononucleosis, hepatitis, or HIV depending on risk factors and symptoms
- Urinalysis to evaluate for kidney disease or infection
Specialized Testing
If the initial workup is negative but symptoms persist, further specialized testing may be warranted based on additional symptoms or risk factors, potentially including:
- Sleep studies to evaluate for sleep disorders
- Cardiac evaluation to assess for cardiac causes of fatigue
- Referral to specialists such as endocrinologists, rheumatologists, or sleep medicine specialists for further evaluation and management.
The most recent and highest quality study 1 suggests that a thorough clinical evaluation is essential to establish the "phenotype" of the individual patient's fatigue, which helps to sharpen the thinking about underlying mechanisms and tailoring of treatment or referral to an appropriately trained professional.
From the Research
Lab Workup for Fatigue
The lab workup for fatigue typically involves a comprehensive approach to diagnose the underlying cause of the condition.
- A complete blood count (CBC) with red cell indices is often used to evaluate fatigue, as it can provide clues to diagnosis and help identify conditions such as anemia 2, 3.
- The reticulocyte count can serve as a useful screen for hemolysis or blood loss, and testing for specific causes of anemia may be performed 2.
- Other useful markers that can be predicted using CBC components include white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), hemoglobin (Hb), mean corpuscular volume (MCV), red cell distribution width (RDW), platelet count, mean platelet volume (MPV), and platelet-to-lymphocyte ratio (PLR) to predict cardiovascular disease (CVD) and metabolic diseases 3.
- However, performance of a battery of diagnostic tests is unlikely to assist with diagnosis, highlighting the importance of a thorough history and physical examination 4.
Diagnostic Approach
A rational approach to diagnosis is paramount due to the broad differential diagnoses that can present as fatigue.
- A comprehensive history and cardiopulmonary, neurologic, and skin examinations can help guide the workup and diagnosis 5.
- Fatigue can be classified as physiologic, secondary, or chronic, and management of secondary fatigue largely depends on treatment of the underlying condition 5, 4.
- Cognitive behavior therapy, exercise therapy, and acupuncture may help with some of the fatigue associated with chronic conditions 5.