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

Workup for Fatigue

The appropriate workup for fatigue should begin with quantitative assessment using a 0-10 scale, followed by focused history, physical examination, and targeted laboratory testing including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and additional tests based on clinical suspicion. 1

Initial Assessment

Fatigue Severity Screening

• Use a standardized scale to quantify fatigue:
  • 0 = no fatigue
  • 1-3 = mild fatigue (requires education only)
  • 4-6 = moderate fatigue (requires evaluation)
  • 7-10 = severe fatigue (requires prompt evaluation) 2, 1

History and Physical Examination

For moderate to severe fatigue (score ≥4), conduct a focused evaluation:

• Medical history:

  • Onset, duration, and pattern of fatigue
  • Associated symptoms (pain, sleep disturbances, mood changes)
  • Current medications and supplements
  • Recent life stressors
  • Sleep patterns and quality 2, 3

• Physical examination focusing on:

  • Vital signs (including orthostatic measurements)
  • Cardiopulmonary assessment
  • Lymph node examination
  • Skin examination (pallor, rashes)
  • Neurological evaluation 3

Laboratory Testing

For moderate to severe fatigue, initial laboratory testing should include:

• Complete blood count (CBC) with differential
• Comprehensive metabolic panel (CMP)
• Thyroid-stimulating hormone (TSH)
• Urinalysis
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
• Iron studies (ferritin, transferrin saturation)
• Vitamin B12 and folate levels
• Vitamin D level 1

It's important to note that laboratory studies affect management in only 5% of patients with fatigue, and if initial results are normal, repeat testing is generally not indicated 4, 5. Excessive testing without clear clinical indications should be avoided to prevent overdiagnosis 6.

Additional Workup Based on Clinical Suspicion

• For patients with sleep complaints: Consider sleep study to evaluate for sleep apnea or other sleep disorders 1, 6
• For patients with cardiac symptoms: ECG, echocardiogram 2, 1
• For patients with respiratory symptoms: Chest X-ray, pulmonary function tests 2
• For patients with depression/anxiety symptoms: Depression and anxiety screening tools 1, 6
• For patients with weight loss, night sweats, or lymphadenopathy: Consider age-appropriate cancer screening 6

Special Considerations

Cancer Survivors

For cancer survivors with fatigue, consider:

• Cardiac evaluation if patient received cardiotoxic treatments
• Thyroid screening if patient received radiation to neck or thorax 2

Chronic Fatigue

If fatigue persists >6 months with post-exertional malaise and other characteristic symptoms, consider myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) using the 2015 National Academy of Medicine diagnostic criteria 3.

Common Pitfalls to Avoid

1. Attributing fatigue solely to one cause without comprehensive evaluation
2. Overlooking psychological factors (depression, anxiety)
3. Dismissing fatigue as "normal" when it significantly impacts quality of life
4. Prescribing exercise without proper assessment (especially harmful in ME/CFS)
5. Failing to recognize medication side effects as potential causes 1

Follow-up

Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 4. Reassess fatigue levels using the standardized scale and adjust the treatment plan based on response.

Remember that fatigue can be classified as physiologic, secondary to medical conditions, or chronic, with each category requiring different management approaches 3. The most common causes include sleep disorders, depression (18.5%), and excessive psychosocial stress, while previously undiagnosed cancer is rare (0.6%) 6.