What is the appropriate workup and treatment for a 20-year-old patient presenting with fatigue?

Fatigue Workup in a 20-Year-Old

Begin by screening fatigue severity using a 0-10 numeric scale; if the score is ≥4, proceed with a focused evaluation targeting treatable conditions rather than extensive laboratory testing, prioritizing medication review, sleep assessment, and screening for depression. 1, 2

Initial Severity Assessment

• Use a numeric rating scale (0-10) to quantify fatigue severity over the past 7 days 3, 1
• Scores of 0-3 (mild) require only routine rescreening at regular intervals with no further workup 1, 2
• Scores of 4-10 (moderate to severe) warrant immediate focused evaluation 1, 2
• Scores ≥7 typically indicate marked functional impairment and decreased physical functioning 1, 2

Focused History

Document the following specific details:

• Onset, pattern, duration, and temporal changes in fatigue 3, 1
• Associated or alleviating factors 1
• Interference with normal functioning and daily activities 1
• Changes in exercise or activity patterns since fatigue onset 4

Assessment of Treatable Contributing Factors

This is the highest-yield component of the evaluation:

Medication Review

• Review ALL current medications including over-the-counter drugs, herbal supplements, and vitamins 4, 3
• Note any recent medication changes 4, 3
• Evaluate for medication interactions causing excessive drowsiness (e.g., combinations of narcotics, antidepressants, antiemetics, antihistamines) 4
• Consider cardiac medications like β-blockers that may cause bradycardia and subsequent fatigue 4, 3

Sleep Evaluation

• Assess sleep quality, quantity, and sleep hygiene practices 3, 1
• Screen for sleep disorders including insomnia and sleep apnea 4, 3
• Evaluate sleep environment and pre-bedtime activities 3
• Note that sleep disturbances are prevalent and fatigued patients often have severely disrupted sleep patterns despite increased time resting 4

Mental Health Screening

• Screen for depression and anxiety, which frequently co-occur with fatigue 3, 1
• Depression is one of the most common causes of persistent fatigue (18.5% of cases) 5
• Note that fatigue and depression are independent conditions with different patterns and one does not necessarily predict the other 4

Activity Level Assessment

• Evaluate ability to accomplish normal daily activities 4, 3
• Assess changes in exercise patterns and degree of deconditioning 4, 3
• Determine current conditioning level before recommending exercise 3

Substance Use

• Screen for alcohol or substance use/abuse that may contribute to or aggravate fatigue 4, 3

Laboratory Studies

Keep initial laboratory testing limited and targeted:

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

Important caveat: Laboratory studies affect management in only 5% of patients, and if initial results are normal, repeat testing is generally not indicated 6. Previously undiagnosed cancer accounts for only 0.6% of cases of persistent fatigue 5.

Physical Examination

• Perform lymph node assessment 2
• Evaluate for hepatosplenomegaly 2
• Conduct thorough review of systems to identify affected organ systems 1

Nutritional Assessment

• Evaluate weight changes, caloric intake, and appetite 4, 3
• Assess for impediments to nutritional intake 4
• Check for fluid and electrolyte imbalances (sodium, potassium, calcium, magnesium) 4
• Consider nutrition expert consultation if substantial abnormalities exist 4, 3

Management Approach

Universal Recommendation

Implement a structured physical activity program with stretching and aerobic exercise 2-3 times weekly for 30-60 minutes, regardless of the underlying cause. 2, 6 This is proven to lower fatigue levels, though convincing fatigued patients requires starting with low-level activities that increase gradually, especially if significantly deconditioned 4.

Targeted Interventions

• Treat any identified underlying causes 3
• Implement good sleep hygiene practices 3
• Address nutritional deficiencies with appropriate supplementation 4
• Consider psychosocial interventions for emotional distress 3
• Consider cognitive behavioral therapy for persistent fatigue 6, 7
• For depression, selective serotonin reuptake inhibitors (fluoxetine, paroxetine, or sertraline) may improve energy 6

What NOT to Do

• Avoid psychostimulants and dietary supplements as they lack efficacy 2
• Avoid extensive imaging studies (chest X-ray, CT, PET/CT) unless red flags are present 2
• Avoid further "fishing expedition" laboratory testing if initial workup is unrevealing 8

Follow-up Strategy

• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 6
• Reassess fatigue severity at each visit 3
• Be aware that fatigue rarely occurs in isolation and often clusters with other symptoms 3, 1

Common Pitfalls to Avoid

• Don't overlook medication side effects as potential contributors—this is commonly missed 3, 1, 2
• Don't pursue extensive laboratory or imaging workup in the absence of specific clinical findings, as this leads to overdiagnosis 5
• Don't assume a purely somatic cause when psychiatric illness (especially depression) accounts for a significant proportion of cases 8, 5