What is the initial workup and treatment for a male presenting with severe fatigue?

Workup for Severe Fatigue in Males

Screen fatigue severity using a 0-10 numeric scale, and if the score is ≥4 (moderate to severe), proceed with a focused evaluation targeting treatable medical conditions, psychiatric disorders, and contributing factors rather than extensive laboratory testing. 1, 2

Initial Severity Assessment

• Use a numeric rating scale (0-10) asking: "How would you rate your fatigue over the past 7 days?" 3, 1
• Scores of 0-3 require only routine rescreening at regular intervals 3, 2
• Scores ≥4 warrant immediate focused evaluation 3, 1, 2
• Scores ≥7 typically indicate marked functional impairment 3, 2

Focused History (Key Elements)

Timing and Pattern:

• Onset, duration, and progression of fatigue 2, 4
• Relationship to exertion (postexertional malaise suggests ME/CFS) 4
• Impact on work, family, and social functioning 2, 5

Associated Symptoms to Identify:

• B symptoms: fever, drenching night sweats, unintentional weight loss >10% over 6 months (suggests malignancy or infection) 1
• Pain, which commonly clusters with fatigue 2
• Respiratory symptoms: cough, dyspnea 1
• Lymphadenopathy or organomegaly 1
• Sleep quality and quantity 2, 5

Contributing Factors:

• Complete medication review (prescription and over-the-counter) as side effects are commonly overlooked 3, 2
• Alcohol and substance use 2
• Psychosocial stressors and occupational demands 6
• Depression screening (accounts for 18.5% of persistent fatigue cases) 6
• Anxiety symptoms 2, 6

Physical Examination Focus

• Cardiopulmonary examination 4
• Neurologic examination 4
• Skin examination 4
• Lymph node assessment 1
• Hepatosplenomegaly evaluation 1

Laboratory Workup

Initial screening tests (the only tests needed for most patients):

• Complete blood count with differential (evaluate cytopenias, leukocytosis, abnormal cells) 1
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, lactate dehydrogenase, albumin 1
• Thyroid-stimulating hormone (TSH) to rule out thyroid dysfunction 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for inflammation 1

Additional testing only if clinically indicated:

• HIV testing if risk factors present 1
• Tuberculosis screening (IGRA or TST) if risk factors present 1
• Laboratory results affect management in only 5% of patients, and repeat testing is generally not indicated if initial results are normal 5

Imaging Studies

Only pursue imaging if red flags are present:

• Chest X-ray if pulmonary symptoms or B symptoms present 1
• CT chest/abdomen/pelvis with contrast if lymphadenopathy, organomegaly, or B symptoms suggest malignancy 1
• PET/CT if lymphoma suspected 1

Important caveat: Previously undiagnosed cancer accounts for only 0.6% of fatigue cases, and anemia/organic causes account for only 4.3% 6. Avoid excessive somatic focus to prevent overdiagnosis 6.

Common Pitfalls to Avoid

• Do not pursue extensive "fishing expedition" laboratory testing if history and initial screening are unrevealing 7, 5
• Do not overlook medication side effects as a reversible cause 3, 2
• Do not miss depression, which is far more common than organic disease 6
• Do not order repeat laboratory tests if initial results are normal without new clinical findings 5
• Avoid exclusively somatic focus when diagnosis remains unclear after initial workup 6

Treatment Approach Based on Findings

For all patients regardless of cause:

• Structured physical activity program with stretching and aerobic exercise (walking, cycling, swimming) 2-3 times weekly for 30-60 minutes 3, 5
  • Exception: Exercise can be harmful in ME/CFS due to postexertional malaise; these patients need pacing strategies instead 4
• Proper sleep hygiene 8, 4
• Healthy diet 4

If depression identified:

• Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, or sertraline) 5

If specific medical condition identified:

• Treat the underlying condition (anemia, thyroid disorder, etc.) 5, 4

If no clear diagnosis after initial workup:

• Schedule regular follow-up visits rather than sporadic urgent appointments 5
• Consider cognitive behavior therapy 8, 5, 4
• Watchful waiting to prevent overdiagnosis 6
• Psychostimulants (methylphenidate, modafinil) are NOT recommended as their efficacy is not proven 3
• Dietary supplements (L-carnitine, coenzyme Q10) are ineffective 3