Fatigue — Full Text

This is a very common symptom.  Patients say they’re “weak.”  Clinicians say “Fatigue,” because to us, “weak” means something else.

STEP 1 — Before any attempt at diagnosis, we have to define what a patient means if they “feel weakness” or “fatigue.”   Some possibilities:

**  Weakness.  In the medical sense, this means a neurological or muscle-fiber disease, preventing muscles from working normally.  Symptoms may include falls, or โ€œdropping things.โ€  Causes of true weakness, some of which may be lethal, include rare conditions like Myasthenia Gravis, Spinal Cord tumors, Guillain-Barrรฉ, ALS (“Lou Gehrig’s Disease”), etc.

With true neuromuscular Weakness, patients may not be able to rise up without boosting themselves with their arms.  On physical exam, we find decreased strength when testing against resistance.  In clinical practice, true neurological weakness is quite rare.

**  Fatigue, on the other hand, is common.  It’s a feeling of being “worn out.”  But if I said, “I’ll give you $1,000 if you lift this suitcase, or kick this ball hard,” you’d muster the strength.  With true neuromuscular weakness, you wouldn’t be able to.

**  Short of Breath (SOB) [a standard medical abbreviation].  True lack of oxygen due to some sort of heart or lung condition, SOB always gets worse on exertion.  Of course, Fatigue can too, but the feeling is different.  A person with SOB is “huffing & puffing.”  A person with Fatigue feels simply weary, doesn’t want to go on.  The difference is critical, because the causes are so different.  See our definition “True” Shortness of Breath. We discuss Shortness Of Breath on its own.

**  Sleepiness.  Daytime nodding-off suggests the diseases Sleep Apnea or Narcolepsy, which are completely different from “Fatigue”.  Some people fail to recognize that they’re sleepy, & hence feel fatigue, because they work double shifts, or work at nights but there’s a construction site next door making noise all day, or the neighbors party all night, etc.

**  Generalized Pain, syndromes such as Fibromyalgia or Polymyalgia Rheumatica.  Here there’s a sense of pain, which isn’t the case with common Fatigue. See our topic Body Aches.

From now on, weโ€™re talking about Fatigue

STEP 2  —  Define the Time Frame.

  • Acute Fatigue — Under 1 month
  • Chronic Fatigue — Over 6 months

Acute fatigue is the most concerning, since a few of the causes might be fatal.  Once 6 months have rolled around and nothing has changed, they’re not going to have a severe infection or cancer.

What about 2-6 months?  If symptoms are progressively getting worse, we lump it with โ€œAcute.โ€  If symptoms remain on a steady level, theyโ€™re heading for chronic.  The work-up is the same for all time periods.

โ€œChronic Fatigueโ€ is not the same as โ€œChronic Fatigue Syndromeโ€ (CFS).  The latter has specific diagnostic criteria, including โ€œ>6 months duration.โ€  This is for research purposes; many patients who donโ€™t meet the case definition may still have true CFS.  Of course, nobody yet knows what causes โ€œtrueโ€ CFS, so no need to quibble.  Work-up & treatment are all the same.

STEP #3  —  Obtain medical History, perform Physical Exam, for possible causes:

Causes of “Fatigue” as a Symptom


โ€ข Heart (a low-grade one) **
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.)


We work up any “Red Flags” — danger signs of possibly serious disease:

  • Fevers
  • Night Sweats
  • Weight Loss

โ€œNight sweatsโ€ means “drenching;” moist pillows or collars donโ€™t count.  I ask if sweat actually drips from pajamas or sheets upon wringing.  In terms of weight loss, we want it documented on our own scales, but Iโ€™m convinced if patients say their clothes are significantly looser.  We can examine the belt, to see if itโ€™s now being tightened from prior worn notches.

If we find Red Flags, we’re going to be lots more aggressive in our diagnostic search.  In addition to the tests noted below, we’d wind up ordering a Chest X-ray and likely a CT Scan of the abdomen & pelvis for Cancers, or Bacterial Infections that aren’t obvious.  Fevers may lead us to obtain tests like cultures of blood, or echocardiogram (for Heart Infection).

The medical history may offer other clues, like Substance Use (or especially Withdrawal), chronic allergy or acid-reflux symptoms, etc. People don’t realize that flare-ups in chronic conditions can cause Fatigue; even if you just broke your toe, the discomfort can wear you out in general.  Prominent symptoms like Cough, Nausea, Diarrhea, Joint Pain, etc. would lead us down those diagnostic pathways [see links to those specific topics].

We perform a brief physical exam, looking for heart murmurs, enlarged liver or spleen, true neurological weakness (especially in hips & shoulders), and suspicious lymph nodes (“swollen glands” in lay terms) that suggest cancer [by the way, whatโ€™s the most ominous lymph node in the body, & why?  Click link for answer].

Depression or Anxiety are statistically the most likely causes of Fatigue.  These may be due to extraneous factors like personal problems, or simply occur on their own.  Still, we always want to rule out serious physical disease.

STEP 4 — Consider some Tests

Assuming our history & physical exam don’t point anywhere, with no Red Flags, some tests are worth doing.  We use our list of possible causes as a guide, but donโ€™t go overboard.  Some simple blood tests to start, that cover just about everything on our list:

Then we have the patient return in 2-3 weeks, long enough to reveal any possible weight loss.  But we’re sure we have a valid telephone number, lest an emergent result require immediate intervention. [I’ve had patients give false ones to avoid a bill; their loss!]

STEP 5  —  Any abnormal lab tests or weight loss usually indicate further testing.

A few comments:

** An elevated Sedimentation Rate / CRP is non-specific.  I find it useful only if very high:

  • Sed Rate >100 suggests metastatic cancer, multiple myeloma, disseminated TB, endocarditis, deep abscess, HIV, or giant cell (temporal) arteritis.
  • Values <50 arenโ€™t useful, unless they continue to rise.
  • Intermediate elevations (60-80) are tough. ย We’d seek symptoms like early morning stiffness and diffuse muscle or joint pains, then follow weight change and blood counts.

**  BEWARE of small lab abnormalities, like just 1-2 decimal points, or like a TSH of 6.0 (normal is <4.5, but nobody with hypothyroidism gets symptoms until it’s >20, & often >100).  โ€œAbnormalโ€ is simply a statistical concept, meaning outside the bell curve of 95% of the general population (>2 standard deviations from the mean).  By definition, 2.5% of all test results should be high, & 2.5% low.  These patients have a higher likelihood of having the disease in question, but donโ€™t necessarily have any illness at all.

  • Statistically, if we perform a test on 20 patients, the odds are that one will be abnormal by pure chance alone.  Likewise if we perform a certain test 20 times on one person.  And also, if we draw 20 lab tests at once (i.e. a Comprehensive Metabolic Panel).
  • Once again, in other words, a test result outside “normal limits” does NOT necessarily mean there’s any disease present.

**  A common and often-missed cause of fatigue is mild muscle toxicity from Statins (common medications to lower cholesterol).  There’s often some sense of muscle aching, but maybe just “fatigue”.  The CK is usually normal or slightly elevated (as opposed to the much rarer, quite painful muscle destruction from statins, Rhabdomyolysis, when the CK is extremely elevated, in the 10,000โ€™s, & can be fatal).  A trial of discontinuing the statin, then trying it again in 2 months (rechallenge), should be diagnostic (but never try if there was rhabdomyolysis).

So after 2-3 weeks, our patient returns for follow-up.

IF ALL RESULTS ARE NORMAL  —  Well, weโ€™ve pretty much covered everything except for maybe Celiac Disease (order a blood tissue-Transglutaminase IgA antibody, but only if there are chronic gastrointestinal symptoms), or the rare Adrenal Insufficiency, which weโ€™d only consider in the event of new generalized โ€œsuntanโ€ (hyperpigmentation) or a documented fall in blood pressure from lying to standing (see Postural Vital Signs) (JFK had this).  The first test for this is an early morning blood test for the hormone Cortisol.

With no abnormal tests, & still no Red Flags, it’s time to explore mood disorders.  We inquire about โ€œstress,โ€ specifically โ€œdepressionโ€ (sadness, urge to cry) and โ€œanxiety.โ€  Other less obvious symptoms may signal Depression, such as low energy, sleep & appetite disturbances, poor concentration, lack of interests, no pleasures, or low libido.  Persons with Anxiety often feel recurrent palpitations, tremors, cold sweaty palms, tingling in hands & mouth, phobias, or episodes of panic.

Most patients are not resistant to the possibility that fatigue may be due to โ€œstress.โ€  โ€œStress,โ€ of course, may range from economic problems [hard to treat] to thoughts of suicide or homicide.  If the patient acknowledges symptoms of depression or anxiety, we explore these worst-case extremes.  Another common source of stress is Domestic Violence, a potentially lethal situation for either patient or possible target.  Rarely, some persons with vague “stress” may be experiencing the beginning of a new psychosis (hallucinations, paranoias, delusions).

If the above mood symptoms are positive, and we’re not concerned about severe mental illness needing psychiatric referral (suicidality, psychosis, bipolar disorder), we’d offer a trial of treatment, either with medication or cognitive behavioral therapy (new term for psychotherapy).  For the occasional patient who refuses to accept it, I suggest that โ€œeven if โ€˜stressโ€™ isnโ€™t causing fatigue, itโ€™s common for any disabling symptom to cause ‘stress.’โ€

Whether or not we institute treatment, we’re sure to reassure the patient regarding all the diseases they donโ€™t have.  This, in and of itself, often helps.  If patients are functioning adequately, no treatment is necessarily indicated.

And if the entire work-up is negative, with no suggestion of a psychological explanation — then we’re left with the diagnosis of exclusion, Chronic Fatigue Syndrome.  Especially if the fatigue persists 6 months and nothing changes.  Itโ€™s a diagnosis unsatisfactory to [& often derided by] many clinicians, quite possibly due to an as-yet-unidentified virus.  We refer to a provider who specializes in it, since there’s no regularly-effective treatment.  And we’d certainly schedule periodic follow-up visits, to monitor for new symptoms, weight loss, and overall life.

What we DON’T DO:

  • DONโ€™T blindly order invasive & expensive tests, like total-body CT scans or MRIs (referred to as a โ€œgrope-o-gram,โ€ like groping in the dark).  If something shows up, the odds are great that it’s not significant, but may lead to possibly-dangerous biopsies
  • DONโ€™T order tests for โ€œchronicโ€ Epstein-Barr Virus, Cytomegalovirus, or Lyme Disease (positive results do NOT prove there’s a disease present)
  • Certain other tests are NOT useful, unless there are suggestive symptoms — these include tests for types of arthritis (the ANA & others), Immunoglobulins, various antibody tests, CK, etc. (lots of people have abnormal results without having any illness)

Thatโ€™s it for โ€œFatigue;โ€ hope this wasnโ€™t too fatiguing.

See also Fatigue for the clinicianโ€™s condensed thought-process when face-to-face with a patient.

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