What is the diagnostic workup for a 19-year-old male with persistent fatigue?

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Last updated: May 22, 2025View editorial policy

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From the Guidelines

The workup for a 19-year-old male with persistent fatigue should begin with a comprehensive history and physical examination, followed by targeted laboratory testing, as recommended by the American Society of Clinical Oncology clinical practice guideline adaptation 1. The initial evaluation should include a focused fatigue history, including onset, pattern, duration, and associated or alleviating factors, as well as an assessment of disease status and treatable contributing factors such as comorbidities, medications, and nutritional issues 1.

Initial Laboratory Tests

Initial blood tests should include:

  • A complete blood count with differential to assess for anemia, white blood cell count abnormalities, or evidence of infection, as suggested by the American Society of Clinical Oncology clinical practice guideline adaptation 1
  • A comprehensive metabolic panel to evaluate liver, kidney, and electrolyte status 1
  • Thyroid function tests (TSH) to rule out hypothyroidism, with consideration of more comprehensive evaluation or referral to a specialist if other symptoms are present 1

Additional Tests

Additional appropriate tests may include:

  • Vitamin B12 and folate levels
  • Inflammatory markers like ESR and CRP
  • A monospot test or EBV serology to rule out infectious mononucleosis
  • Screening for depression and anxiety using standardized questionnaires like PHQ-9 or GAD-7, as mental health conditions frequently present with fatigue
  • Sleep quality assessment, potentially including screening for sleep apnea if indicated by history

Specialized Testing

If the patient reports exercise intolerance, muscle weakness, or post-exertional malaise, consider specialized testing for chronic fatigue syndrome/myalgic encephalomyelitis. Depending on risk factors and history, testing for HIV, hepatitis, Lyme disease, or other infectious causes may be warranted. Management should target any identified underlying causes while addressing lifestyle factors including sleep hygiene, balanced nutrition, appropriate physical activity, and stress management techniques.

From the Research

Initial Evaluation

The workup for a 19-year-old male with persistent fatigue should begin with a comprehensive history and physical examination to guide the diagnosis and identify potential underlying causes 2, 3, 4, 5.

Common Causes of Fatigue

  • Sleep disorders and sleep-related disorders of breathing
  • Depression (18.5%) 2
  • Excessive psychosocial stress 2
  • Previously undiagnosed cancer (0.6%) 2
  • Anemia and other organic causes (4.3%) 2

Diagnostic Approach

Investigations beyond the history, physical examination, and simple laboratory tests are needed only in the presence of additional symptoms or findings 2, 5.

Laboratory Tests

Laboratory tests, such as liver function tests, may be altered in thyroid disorders, and interpretation should be done with caution 6.

Management

Treatment of fatigue should include a structured plan for regular physical activity, such as walking, and may involve cognitive behavioral therapy and individualized exercise therapy 3, 4, 5.

Special Considerations

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, severe, and potentially debilitating disorder that may be considered in the differential diagnosis, and patients should be educated about pacing their activity to avoid postexertional malaise 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fatigue in Adults: Evaluation and Management.

American family physician, 2023

Research

Fatigue: an overview.

American family physician, 2008

Research

Approach to Fatigue: Best Practice.

The Medical clinics of North America, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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