What is the diagnostic workup and management for a male presenting with chronic fatigue?

Chronic Fatigue Workup in Males

Begin by screening fatigue severity using a 0-10 numeric rating scale, and if the score is ≥4, proceed immediately with a focused evaluation targeting treatable medical conditions rather than extensive laboratory testing. 1, 2

Initial Severity Assessment

• Use a numeric rating scale (0-10) asking the patient to rate their fatigue over the past 7 days 1, 2
• Scores of 0-3 (mild) require only routine rescreening at regular intervals with no further workup 1
• Scores of 4-10 (moderate to severe) warrant immediate focused evaluation 1, 2
• Scores ≥7 typically indicate marked decrease in physical functioning and require urgent attention 1

Focused History Components

The history is the most important diagnostic tool and should systematically evaluate specific contributing factors rather than casting a wide net. 1, 2

Fatigue Characteristics

• Document onset, pattern, duration, and changes over time 1
• Identify associated or alleviating factors 1
• Assess interference with normal functioning and daily activities 1
• Obtain the patient's self-assessment of potential causes 1

Treatable Contributing Factors (Assess Each Systematically)

• Pain assessment: Pain commonly clusters with fatigue and requires effective treatment 1
• Emotional distress screening: Use the two-question depression screen:
  • "In the last month, have you often felt dejected, sad, depressed or hopeless?" 3
  • "In the last month, did you experience significantly less pleasure than usual with the things you normally like to do?" 3
• Sleep disturbance evaluation: Assess sleep quality, quantity, hygiene, and screen for sleep apnea, restless leg syndrome, and periodic limb movement 3, 1
• Complete medication review: Side effects are commonly overlooked as contributors to fatigue 1, 2
• Alcohol and substance use screening: Misuse may contribute significantly to fatigue 1, 2

Review of Systems

• Conduct a thorough review to identify affected organ systems 1
• Specifically assess for thyroid symptoms (cold intolerance, weight changes, constipation) 3
• Evaluate for cardiovascular symptoms (chest pain, dyspnea, exercise intolerance) 3
• Screen for infectious symptoms (fever, night sweats, weight loss) 3

Physical Examination

Focus the examination on identifying specific treatable conditions rather than performing a routine general exam. 2

• Lymph node assessment for lymphadenopathy 2
• Hepatosplenomegaly evaluation 2
• Thyroid palpation for enlargement or nodules 3
• Cardiovascular examination including blood pressure 3
• Mental status examination 3

Laboratory Workup

Initial screening tests should be limited and targeted, as predictive values of laboratory tests are generally low in chronic fatigue. 3, 2

Minimum Battery of Tests

• Complete blood count with differential (to assess for anemia, infection, or hematologic malignancy) 2
• Comprehensive metabolic panel (to evaluate liver and kidney function, electrolyte balance, glucose) 2
• Thyroid-stimulating hormone (TSH) (hypothyroidism is a highly treatable cause) 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for inflammation 2

Additional Tests Based on Clinical Suspicion

• Free T4 if TSH is abnormal 3
• Vitamin B12, folate, and vitamin D levels if nutritional deficiency suspected 3
• Testosterone level in males with additional symptoms of hypogonadism (decreased libido, erectile dysfunction) 3

Imaging Studies

Imaging should only be pursued if red flags are present on history or physical examination. 2

• Chest X-ray if respiratory symptoms or lymphadenopathy present 2
• CT chest/abdomen/pelvis with contrast if constitutional symptoms suggest malignancy 2
• PET/CT only if strong suspicion for occult malignancy 2

Common Pitfalls to Avoid

• Do not perform extensive "fishing expedition" laboratory testing in the absence of clinical suspicion, as this is fruitless and may lead to false positives 2
• Do not overlook medication side effects as potential contributors—this is one of the most commonly missed causes 1, 2
• Do not attribute symptoms to "chronic fatigue syndrome" until all treatable medical and psychiatric conditions have been excluded 3, 1
• Do not forget that fatigue rarely occurs in isolation and often clusters with pain, depression, and sleep disturbance 1

Diagnostic Criteria for Chronic Fatigue Syndrome (Only After Exclusion)

Chronic fatigue syndrome is a clinical diagnosis that can only be made when other disease processes are excluded. 4

• Severe fatigue lasting longer than 6 months not relieved with rest 4
• Plus at least 4 of the following: postexertional malaise, unrefreshing sleep, impaired memory or concentration, muscle pain, polyarthralgia, sore throat, tender lymph nodes, or new headaches 4

Initial Management Approach

Regardless of the underlying cause, all patients with chronic fatigue should begin a structured physical activity program. 2

• Promote a consistent pattern of activity, rest, and sleep 5
• Structured physical activity with stretching and aerobic exercise 2-3 times weekly for 30-60 minutes 2
• Gradual return to normal activity levels 5
• Treat identified contributing factors (pain, depression, sleep disturbance, hypothyroidism, anemia) 3, 1
• Psychostimulants and dietary supplements are not recommended due to lack of efficacy 2
• Antidepressants may be tried on a pragmatic basis if depression is present 5, 6