1.  Define “Fatigue” — Distinguish from other symptoms, esp. true “weakness”:

  • Weakness” = Neurologic diseases, rare but possibly very serious.  Patient may fall, or drop things. Identified by finding actual muscle weakness when testing patient’s strength
  • Fatigue” = feeling worn out, but muscle strength is normal when tested
  • Shortness of Breath = Heart or Lung disease.  Suspected if patient feels they “huff & puff” with simple exertion
  • Sleepiness = nodding off in daytime, suggests Sleep Apnea or Narcolepsy
  • Aches” suggest muscle disease like fibromyalgia, or more serious conditions. See Body Aches

2.  Define Time Frame:

  • Acute Fatigue  =  โ‰ค1 month (more concerning)
  • Chronic Fatigue  =  >6 months (unlikely to be dangerous)
  • If 2-6 months  =  “Acute” if getting worse; “Chronic” if staying the same

3.  Consider Possible Diagnoses

  • Acute Fatigue, <1-2 weeks, we’d think Viral Infection (could include Covid-19), also Anxiety, Depression
    • Every setting has its own way to address Covid before letting a patient in the door. The rest of this topic assumes we’re not dealing with it.
  • Acute Fatigue, going on 2-4 wks: statistically, most likely Anxiety or Depression, but we begin to consider other causes in the table below

Causes of “Fatigue” as the Main Symptom


โ€ข Heart (a low-grade one) **
โ€ข Simple Virus **
โ€ข Bacterial (one that’s not xxxobvious)**
โ€ข Mononucleosis **
โ€ข HIV
โ€ข Hepatitis (acute or chronic)
โ€ข Tuberculosis
โ€ข Other

IDIOPATHIC (Unknown Cause)

โ€ข Chronic Fatigue Syndrome (whether meets the CFS case-definition or not)

โ€ข Blood Abnormalities xxxsodium, potassium, xxxcalcium, etc. **
โ€ข Kidney Failure
โ€ข Liver Failure: acute / chronic

โ€ข Diabetes
โ€ข Hypothyroidism
โ€ข Hyperthyroidism
โ€ข Adrenal Insufficiency
โ€ข Pituitary Insufficiency   

**  Not likely once symptom has become Chronic
โ€ข Cancer (various) **
โ€ข Depression
โ€ข Anxiety
โ€ข Drugs / Alcohol / Medicines
โ€ข Drug Withdrawal
โ€ข Anemia (mod.-severe)
โ€ข Celiac Disease
โ€ข Malnutrition
โ€ข Rheumatologic disorders
xxx(see Joint Pain)
โ€ข Any Chronic Condition that’s xxbothersome (stomach acid, xxallergies, etc.)


4.  Think about possible Red Flags 

May be serious (e.g. cancer), get CT Scans if no diagnosis from basic lab tests (below):

  • Fevers (ongoing)
  • Night Sweats (drenching)
  • Weight Loss

5.ย  Some Possible Lab Tests if no clear diagnosis from History & Physical Exam:

6.  Patient returns in 3 weeks  โ†’ review labs and Check Weight

  • Pursue any significant lab abnormalities
  • If significant weight loss, needs CT Scans chest, abdomen, pelvis, & more work-up

7. No Weight Loss & All Tests Normal (No Red Flags)

  • Depression or Anxiety are most likely diagnoses, often due to personal stressors.  Treat these if any possibility
    • If Depression, essential to exclude thoughts of suicide
  • Essential to exclude possible Domestic Violence (esp. for vulnerable persons)
  • Chronic Fatigue Syndrome is default diagnosis of exclusion (nothing else), symptoms often lasting many months
  • Ongoing follow-up to be sure no Red Flags develop, no new symptoms needing work-up

See Fatigue โ€” Full Text for more in-depth explanations and discussions.

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