What is the initial workup for a patient presenting with fatigue?

Initial Workup for Fatigue

Begin by screening fatigue severity using a 0-10 numeric rating scale, and if the score is ≥4, proceed with targeted laboratory testing (CBC with differential, comprehensive metabolic panel, TSH, ESR/CRP) along with a focused history examining medications, sleep, mood, and activity level—extensive imaging is not indicated unless red flags are present. 1, 2

Severity Screening

• Ask patients to rate fatigue on a 0-10 scale over the past 7 days, where 0 = no fatigue and 10 = worst imaginable 3, 1
• Scores 0-3 (mild): No further workup needed; rescreen at regular intervals 3, 2
• Scores 4-6 (moderate): Proceed with focused evaluation 3
• Scores ≥7 (severe): Indicates marked functional impairment requiring immediate comprehensive assessment 3, 1

Focused History

Timing and Pattern:

• Document onset, duration, pattern, and changes over time 3, 2
• Determine if fatigue is acute (weeks), subacute (months), or chronic (>6 months) 4, 5
• Assess whether fatigue preceded or followed any life changes, illnesses, or treatments 3

Medication Review:

• Review ALL medications including prescription, over-the-counter, herbal supplements, and vitamins 1, 2
• Specifically evaluate sleep aids, pain medications, antiemetics, beta-blockers, and sedating medications 3, 2
• Note recent medication changes or additions 2

Contributing Factors:

• Sleep: Assess quality, quantity, sleep hygiene, and screen for sleep apnea or insomnia 2, 5
• Mood: Screen for depression (present in 18.5% of fatigue cases) and anxiety 1, 2, 5
• Activity level: Evaluate deconditioning, exercise patterns, and ability to perform daily activities 3, 2
• Nutrition: Document weight changes, caloric intake, appetite, and fluid balance 3, 2
• Substance use: Assess alcohol and illicit drug use 3, 2
• Pain: Evaluate presence and severity of pain 2

Red Flags Requiring Expanded Workup:

• Unintentional weight loss, fever, night sweats 3
• New pulmonary complaints or respiratory symptoms 3, 2
• Lymphadenopathy or organomegaly on exam 1, 2
• Fatigue that begins or significantly worsens 6-12 months after any prior treatment 3

Physical Examination

• Assess volume status and orthostatic vital signs 3
• Calculate body mass index 3
• Perform lymph node examination 1
• Evaluate for hepatosplenomegaly 1
• Conduct focused cardiopulmonary and neurologic examinations 4

Laboratory Testing

Initial Panel (for scores ≥4):

• Complete blood count with differential to evaluate anemia, infection, or hematologic malignancy 3, 1, 2
• Comprehensive metabolic panel to assess electrolytes, hepatic function, and renal function 3, 1, 2
• Thyroid-stimulating hormone (TSH) 3, 1, 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for inflammation 1, 2

Additional Testing Only If Clinically Indicated:

• Fasting glucose or hemoglobin A1c if diabetes suspected 3
• HIV testing and tuberculosis screening if risk factors present 2
• Liver function tests if hepatic disease suspected 3

Important Caveat: Laboratory abnormalities affect management in only 5% of patients with fatigue 6. If initial results are normal, repeat testing is generally not indicated unless new symptoms develop 6, 5. Previously undiagnosed cancer accounts for only 0.6% of fatigue cases 5.

Imaging Studies

• Chest X-ray: Only if respiratory symptoms or pulmonary pathology suspected 1, 2
• CT chest/abdomen/pelvis or PET/CT: Only pursue if red flags present (lymphadenopathy, organomegaly, masses, unexplained weight loss) 1
• Routine imaging in the absence of concerning findings leads to overdiagnosis and should be avoided 5

Management Regardless of Cause

• Implement structured physical activity program with stretching and aerobic exercise (walking) 2-3 times weekly for 30-60 minutes 1, 6
• Optimize sleep hygiene 2, 6
• Address nutritional deficiencies if identified 2
• Treat underlying conditions (depression, anemia, thyroid dysfunction) when present 6, 4
• Schedule regular follow-up visits rather than sporadic urgent appointments 6

Avoid: Psychostimulants and dietary supplements lack efficacy and are not recommended 1. Exercise can be harmful in myalgic encephalomyelitis/chronic fatigue syndrome due to postexertional malaise 4.