Fatigue

General Approach

• Differentiate sleepiness and fatigue

  • Sleepiness: Falls asleep while inactive

  • Fatigue

    • Low energy worse with activity and not improved with sleep

    • Chronic fatigue: Symptoms lasting > 6 months

• Identify how fatigue affects activities of daily living

• ROS (malignancy): Fever, night sweats, unintentional weight loss

• Review medications to identify sedatives and stimulants

• Physical exam: Evaluate for conjunctival pallor, lymphadenopathy, goiter, muscular weakness, edema, rash, depressed mood

• Diagnostics

  • Labs

    • Change management in approximately 5% of cases

    • Consider CBC, CMP, TSH, fingerstick glucose, HbA1c, beta-hCG, testosterone, ESR, monospot, Lyme IgG/IgM, HIV 4th generation, urine drug screen

  • Sleep study

• Counseling

  • Explain that fatigue is common and one-third of cases have no identifiable etiology

  • Request that patient keep a sleep diary for at least 2 weeks

Differential Diagnosis

Lifestyle and Sleep

• Stressful lifestyle (e.g. poverty)

• Sedentary lifestyle

  • Recommend 150 minutes aerobic exercise per week

  • Consider physical therapy if concerned about deconditioning

• Poor sleep hygiene

  • Sleep patterns

    • Inadequate sleep (< 8 hours per night)

    • Irregular sleep schedule

    • Daytime naps > 1 hour

  • Stimulants: Exercise < 1 hour before bed, caffeine, nicotine, medications

  • Environment: Excessive light, electronics in bedroom

  • Sleep disturbance: Alcohol, nocturia, pain

• Sleep disorders

  • Insomnia

  • Obstructive sleep apnea

  • Narcolepsy

Anemia

Microcytic/normocytic: Obtain ferritin, TIBC, serum iron

• Iron deficiency anemia

• Anemia of chronic disease

  • May be associated with

    • Common conditions: Heart failure, CKD, DM type 2

    • Inflammatory bowel disease: Crohn’s, ulcerative colitis

    • Autoimmune: Rheumatoid arthritis, lupus

    • Infections: Tuberculosis, HIV/AIDS

    • Malignancy

  • If etiology is uncertain

    • Ensure that malignancy screening is up to date, i.e. FOBT/colonoscopy, mammogram, low-dose CT

    • Consider BNP, CMP, HbA1c, FOBT, ESR, CRP, anti-CCP, ANA, PPD, HIV 4th generation, CXR, echocardiogram

• For pediatric patients, also consider

  • Lead toxicity: Blood lead level > 5 mcg/dL

  • Thalassemia: RBC count (elevated), LDH (elevated), haptoglobin (low), peripheral smear (abnormal morphology)

Macrocytic: Obtain B12/folate level +/- methylmalonic acid (MMA), TSH, CMP, GGT

• Megaloblastic: B12/Folate deficiency

• Non-megaloblastic: Consider hypothyroidism, liver disease, alcohol abuse

Metabolic/Endocrine

• Hypothyroidism

• Hypo/hyperglycemia

  • Pediatric: Diabetes mellitus type 1

  • Pediatric and adult: Diabetes mellitus type 2

• Hyponatremia

  • Hyponatremia etiologies

  • Hypoadrenalism (Addison disease)

    • Anorexia, weight loss, weakness, hyponatremia

    • Schedule morning cosyntropin stimulation test

• Primary male hypogonadism (low testosterone)

Neuropsychiatric

• Depression

  • Perform PHQ 9 consider starting medication/CBT for score ≥ 5

  • Escitalopram 10 mg qd and follow-up in 4 weeks (MDD 30 mg qd)

• Diagnosis of Exclusion

  • Fibromyalgia

  • Chronic fatigue syndrome

    • Must meet all major criteria: Duration > 6 months, does not improve with rest, results in ≥ 50% reduction in activity

    • See vignette for additional physical and minor criteria

    • Start SSRI (see depression above) and/or CBT

Other Considerations

• Pregnancy: Obtain beta-hCG in all reproductive-age females

• Substance abuse

  • Opioid abuse

  • Stimulant withdrawal

• Infectious disease

  • Mononucleosis

  • Lyme disease

  • HIV/AIDS

• Malignancy including chronic lymphocytic leukemia

• Rheumatic disease including systemic lupus erythematosus