1. In all patients complaining of fatigue, include depression in the differential diagnosis.
  2. Ask about other constitutional symptoms as part of a systematic approach to rule out underlying medical causes in all patients complaining of fatigue.
  3. Exclude adverse effects of medication as the cause in all patients complaining of fatigue.
  4. Avoid early, routine investigations in patients with fatigue unless specific indications for such investigations are present.
  5. Given patients with fatigue in whom other underlying disorders have been ruled out, assist them to place, in a therapeutic sense, the role of their life circumstances in their fatigue
  6. In patients whose fatigue has become chronic, manage supportively, while remaining vigilant for new diseases and illnesses.

Red Flags

  • Recent onset in a well elderly person
  • Focal neuro deficits (CNS malignancy, MS)
  • Inflammatory signs or joint pain (autoimmune)
  • Lymphadenopathy, weight loss (Malignancy)
  • Chest pain/Dyspnea
  • Fever


  • Psychiatric/Psychogenic (50%)
    • Depression
    • Anxiety
    • Somatization
    • Substance use
    • Malnutrition
  • Pharmacologic
    • Antihypertensives, antidepressants, hypnotics
  • Endocrine-metabolic
    • Hypothyroidism
    • Diabetes mellitus
    • Pitutiary insufficiency
    • Hypercalcemia
    • Adrenal insufficiency
    • Chronic renal failure
    • Hepatic failure
  • Neoplastic
  • Infectious
    • Endocarditis
    • Tuberculosis
    • Mononucleosis
    • Hepatitis
    • Parasitic disease
    • HIV
    • CMV
  • Cardiopulmonary
    • Anemia
    • CHF
    • COPD
  • Rheumatological
  • Sleep disorder
  • Idiopathic (chronic fatigue, fibromyalgia)


  • Distinguish fatigue from somnolence, dyspnea, muscle weakness
  • Temporal features
    • Abrupt or gradual onset
    • Related to event/illness
    • Related to exertion and improves with rest (suggests organic)
  • Weight loss, night sweats
  • Impact on life
  • Psychiatric illness (Depression, anxiety, somatoform, substance use)
  • Sleep
  • Medications, Alcohol, Drugs

Physical Exam

  • General appearance
  • Lymphadenopathy
  • Thyroid (Goiter, nodule, ophthalmologic changes)
  • Cardiopulmonary (CHF, lung disease)
  • Neurologic (Muscle bulk, tone, strength, reflex, sensory, cranial nerve)


Consider delaying 4w unless fatigue >3mo

  • CBC
  • Electrolytes (glucose, creatinine)
  • LFT
  • TSH
  • Pregnancy test
  • UA
  • Consider
    • Celiac screen (Anti-TTG, IgA)
    • CK if pain or muscle weakness
    • Tuberculosis, HIV, Hepatitis C (born 1945-1965)

Target goals

  • Activities of daily living
  • Return to work
  • Maintain interpersonal relationships
  • Perform daily exercise


  • CBT
  • Graded exercise therapy (eg. daily 30 minute walk)
  • Sleep hygiene
  • Support Groups
  • Follow-up

Chronic Fatigue Syndrome (Systemic Exertion Intolerance Disease)

  • >6 months duration, consider Chronic fatigue syndrome, requires all of:
    1. Impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities
      • Accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest;
    2. Post-exertional malaise
    3. Unrefreshing sleep
    4. And at least one of: Cognitive impairment or Orthostatic intolerance
  • Treatment
    • Treat comorbid (sleep disorder, mood)
    • Psychotherapy
    • Graded exercise therapy