Fatigue – UpToDate

Fatigue can be manifested as
  • difficulty or inability initiating activity (perception of generalized weakness);
  • reduced capacity maintaining activity (easy fatiguability); and
  • difficulty with concentration, memory, and emotional stability (mental fatigue)
  • Fatigue should be distinguished from somnolence, dyspnea, and muscle weakness

Patients with organ-based medical illness often associate their fatigue with activities they are unable to complete. In contrast, patients with fatigue that is not organ-based are tired all the time; their fatigue is not necessarily related to exertion, nor does it improve with rest.

1  In all patients complaining of fatigue, include depression in the differential diagnosis.


  1. Psychogenic: depression, anxiety, Somatization disorder, life stresses,
  2. Sleep: OSA, esophageal reflux, allergic rhinitis, psychologic causes
  3. Endocrine: DM, hypothyroidism, apathetic hyperthyroidism, malnutrition / drug addiction, Hypercalcemia, pituitary insufficiency, adrenal insufficiency, CKD, hepatic failure
  4. Infection: endocarditis, TB, mono, hepatitis, parasitic dz, HIV, CMV
  5. CV: CHF, COPD
  6. Inflammatory: Rheumatoid dz, SLE, PMR
  7. Substance abuse / drugs
  8. Neoplastic-hematologic: occult malignancy, severe Anemia
  9. Idiopathic dx by exclusion: idiopathic chronic fatigue, CFS, fibromyalgia

2  Ask about other constitutional symptoms as part of a systematic approach to rule out underlying medical causes in all patients complaining of fatigue.

  • Onset – abrupt or gradual, related to event or illness?
  • Duration and daily pattern, Course – stable, improving or worsening?
  • Factors that alleviate or exacerbate symptoms
  • Impact on daily life – ability to work, socialize, participate in family activities & Accommodations that patient/family has made to adjust to fatigue symptoms
  • Sleep: quantity & quality & whether or not sleep improves symptoms
  • Thyroid symptoms
  • Social: EtOH, drugs, medications
Red flags (constitutional symptoms):
  • Fever, weight loss, night sweats
  • neurological deficits, ill-appearing
Screening for psychiatric disorders
  • depression, anxiety disorders
  • somatoform disorders
  • substance abuse
  • victims of domestic violence
  • General appearance: level of alertness, psychomotor agitation or retardation, grooming
  • Presence of lymphadenopathy
  • Evidence of thyroid disease: goiter, thyroid nodule, ophthalmologic changes
  • Cardiopulmonary examination: signs of congestive heart failure and chronic lung disease
  • Neurologic examination:
    • muscle bulk, tone, and strength;
    • deep tendon reflexes;
    • sensory and cranial nerve evaluation

3  Exclude adverse effects of medication as the cause in all patients complaining of fatigue.

  1. Hypnotics
  2. Antihypertensives
  3. Antidepressants
  4. Drug abuse and drug withdrawal / EtOH

4  Avoid early, routine investigations in patients with fatigue unless specific indications for such investigations are present.

Extensive laboratory evaluation in the absence of a positive history or physical examination are of little diagnostic utility in the evaluation of the fatigued patient

Reasonable initial laboratory studies to obtain include:

  • Complete blood count with differential
  • Chemistry screen (including electrolytes, glucose, renal and liver function tests)
  • Thyroid stimulating hormone
  • Creatine kinase, if pain or muscle weakness present

Screen for HIV / Hep C
ESR in older pt to r/o polymyalgia rheumatica or giant cell arteritis

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.

  1. Acknowledge the patient’s complaints as real and potentially debilitating.
  2. Act as a guide in establishing therapeutic goals:
    • Accomplishing the activities of daily living
    • Returning to work
    • Maintaining interpersonal relationships
    • Performing some form of daily exercise
  3. Effective Tx: cognitive behavioral therapy (CBT) and graded exercise therapy

Other measures that may be useful include:

  • Provision of general sleep hygiene advice and discouraging over-sleeping
  • Provision of patient education brochures and other materials, discussion of various aspects of chronic fatigue, and referral to support groups
  • Iron therapy in nonanemic patients with low serum ferritin may improve symptoms of fatigue

6  In patients whose fatigue has become chronic, manage supportively, while remaining vigilant for new diseases and illnesses.

  • Establishing a trusting clinician-patient relationship and defining appropriate therapeutic goals is important
  • Brief regularly scheduled appointments preferred over prn appointments to monitor progress

Chronic Fatigue Syndrome (CFS) Dx:
  1. unexplained fatigue > 6mo, not alleviated by rest and causes impact on lifestyle
  2. +≥ 4 associated symptoms:
    • Impairment of short-term memory or concentration causing a ↓ in function
    • Sore throat
    • tender cervical or axillary LN
    • Muscle pain
    • Polymyalgia: Multi-joint pain with no swelling or redness
    • New headache
    • unrefreshing sleep
    • Post-exertional malaise >24hr

  • UpToDate 2015
Posted in 28 Fatigue, 99 Priority Topics, Endo, FM 99 priority topics

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