What are the common causes of fatigue?

Common Causes of Fatigue

Fatigue is a multifactorial symptom with identifiable treatable causes that must be systematically evaluated, including pain, sleep disturbances, anemia, depression, medications, nutritional deficiencies, and decreased physical activity. 1

Primary Causative Factors to Assess

Physical/Medical Causes

• Anemia is a fundamental cause requiring complete blood count and iron studies evaluation 1
• Sleep disorders affect 30-75% of patients with fatigue, ranging from insomnia to hypersomnia, and represent a frequently overlooked contributor 2, 1
• Pain commonly clusters with fatigue and requires concurrent assessment and effective treatment 2, 1
• Medication side effects, particularly from sedating drugs, are common contributors that must be systematically reviewed 2, 1
• Nutritional deficiencies, including weight changes, inadequate caloric intake, and electrolyte imbalances, contribute significantly 1
• Endocrine dysfunction, particularly thyroid disorders, is frequently among the first diagnostic considerations 3
• Comorbidities correlate with increased fatigue severity, with patients having 3-7 comorbidities experiencing significantly higher fatigue levels 2

Psychological/Behavioral Causes

• Depression co-occurs in 25-33% of patients with fatigue and represents the strongest predictor of fatigue intensity in many conditions 2, 1
• Anxiety frequently accompanies fatigue and requires independent assessment 1
• Emotional distress both causes and exacerbates fatigue symptoms 2
• Poor sleep hygiene, including irregular sleep schedules, daytime napping, and caffeine/alcohol consumption before bed, is a frequent but modifiable contributor 2, 1

Lifestyle Factors

• Decreased physical activity paradoxically worsens fatigue symptoms rather than relieving them 1
• Lower socioeconomic status (income <$50,000) correlates with more severe fatigue 2
• Polypharmacy correlates with higher fatigue scores across multiple dimensions 2

Clinical Evaluation Approach

Initial Screening

• Use a numeric rating scale (0-10) to quantify severity: mild (1-3), moderate (4-6), severe (7-10) 1
• Scores of 4 or higher warrant focused evaluation 1

Detailed Assessment Components

• Onset and pattern: When did fatigue begin, how has it changed over time, what factors worsen or alleviate it 2, 1
• Functional impact: Specific effects on daily activities, work performance, and social relationships 2, 4
• Review of systems: Comprehensive evaluation to identify affected organ systems and guide diagnostic workup 2, 1
• Associated symptoms: Fatigue rarely occurs alone—assess for concurrent pain, sleep disturbance, emotional distress, and cognitive symptoms 2, 1

Laboratory Evaluation

• Core tests for moderate-to-severe fatigue: Complete blood count, thyroid-stimulating hormone, basic metabolic panel, liver function tests, and inflammatory markers like C-reactive protein 1
• Laboratory results affect management in only approximately 5% of cases, but are essential to rule out treatable causes 1, 4
• If initial laboratory results are normal, repeat testing is generally not indicated 4

Critical Pitfalls to Avoid

• Overlooking psychological causes such as depression and anxiety leads to inadequate treatment, as these are among the most common and treatable contributors 2, 1
• Ignoring medication side effects can perpetuate or worsen fatigue—systematically review all prescription and over-the-counter medications 2, 1
• Missing sleep disorders results in inadequate treatment, despite their high prevalence and significant impact 2, 1
• Assuming fatigue is proportional to disease burden without considering that patients with lower functional status, more comorbidities, and polypharmacy experience disproportionately severe fatigue 2
• Failing to assess functional impact misses the true burden of fatigue on quality of life, as patients consistently report inability to perform valued activities with family and friends 2

Special Considerations

• Fatigue commonly clusters with other symptoms rather than occurring in isolation—assess the entire symptom complex 2, 1
• Cancer treatment (chemotherapy, radiation, medications) represents a major contributor in oncology populations 2
• Family members may recognize functional changes before patients do, making collateral history valuable 5
• Patients with longer time since diagnosis (≥4 years) often have more barriers to reporting and managing fatigue 2