What is the approach to a fatigue workup?

Approach to Fatigue Workup

The approach to fatigue workup should begin with a comprehensive laboratory evaluation including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, urinalysis, erythrocyte sedimentation rate, C-reactive protein, iron studies, vitamin B12, folate, and vitamin D levels to identify underlying treatable conditions. 1

Classification of Fatigue

Fatigue can be classified into three main categories:

1. Physiologic fatigue: Related to lifestyle factors
2. Secondary fatigue: Due to underlying medical conditions
3. Chronic fatigue: Including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) 2

Initial Assessment

History and Physical Examination

• Assess fatigue severity using a standardized scale (0-10):

  • 0: No fatigue
  • 1-3: Mild fatigue (requires education only)
  • 4-6: Moderate fatigue (requires evaluation)
  • 7-10: Severe fatigue (requires prompt evaluation) 1

• Focus on identifying:

  • Medication side effects
  • Sleep disturbances (present in 30-75% of patients with fatigue)
  • Depression and anxiety (present in up to 33% of patients)
  • Pain and musculoskeletal symptoms
  • Nutritional status and weight changes 1

Laboratory Evaluation

• First-line tests:

  • Complete blood count (anemia)
  • Comprehensive metabolic panel (electrolyte imbalances, renal/liver dysfunction)
  • Thyroid-stimulating hormone (thyroid dysfunction)
  • Urinalysis
  • Erythrocyte sedimentation rate and C-reactive protein (inflammation)
  • Iron studies
  • Vitamin B12 and folate levels
  • Vitamin D level 1

• Important note: Laboratory studies affect management in only 5% of patients, and if initial results are normal, repeat testing is generally not indicated 3

Management Strategies

Physiologic Fatigue

1. Exercise intervention:

   • Implement structured exercise program combining aerobic and resistance exercises
   • Start with 150 minutes of moderate aerobic exercise per week
   • Consider referral to physical therapist for patients at higher risk of injury 1

2. Sleep hygiene:

   • Maintain regular sleep schedule
   • Limit daytime napping
   • Avoid caffeine and alcohol before bedtime
   • Create comfortable sleep environment 1

3. Energy conservation:

   • Schedule activities during peak energy times
   • Delegate non-essential tasks
   • Use labor-saving devices 1

Secondary Fatigue

• Address underlying conditions:
  • Correct anemia
  • Normalize electrolyte imbalances
  • Optimize caloric intake
  • Treat depression/anxiety if present 1, 2

Chronic Fatigue/ME/CFS

• Cognitive behavioral therapy to address negative thought patterns
• Pacing activities to avoid postexertional malaise (especially important in ME/CFS)
• Note: Exercise can be harmful to patients with ME/CFS as it can trigger postexertional malaise 2

Pharmacologic Interventions

• For episodic situations requiring alertness:

  • Caffeine
  • Modafinil 3

• For concurrent depression:

  • Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline) 1, 3

• For severe persistent fatigue:

  • Consider psychostimulants after ruling out contraindications 1

Follow-up

• Schedule regular follow-up visits rather than sporadic urgent appointments
• Reassess fatigue levels using standardized scale
• Adjust treatment plan based on response 1, 3

Common Pitfalls to Avoid

• Attributing fatigue solely to one cause without comprehensive evaluation
• Overlooking psychological factors
• Dismissing fatigue as "normal" when it significantly impacts quality of life
• Prescribing exercise without proper assessment of underlying conditions (especially for ME/CFS)
• Failing to recognize medication side effects as potential causes of fatigue 1
• Failing to recognize that stress can cause false elevations in prolactin levels 1