What is the diagnostic approach for fatigue?

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Last updated: February 20, 2025View editorial policy

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From the Guidelines

The diagnostic approach for fatigue should begin with a comprehensive history and physical examination, focusing on the onset, pattern, duration, and associated or alleviating factors of fatigue, as well as an evaluation of disease status and treatable contributing factors, as recommended by the American Society of Clinical Oncology clinical practice guideline adaptation 1. The approach should include:

  • A focused fatigue history, including onset, pattern, duration, and change over time, as well as associated or alleviating factors 1
  • An evaluation of disease status, including the risk of recurrence based on stage, pathologic factors, and treatment history 1
  • An assessment of treatable contributing factors, such as comorbidities, medications, alcohol/substance abuse, nutritional issues, and deconditioning 1
  • A review of systems to determine if other symptoms substantiate suspicion for recurrence or other underlying conditions 1
  • Consideration of laboratory evaluation based on the presence of other symptoms, onset, and severity of fatigue, including complete blood count, comprehensive metabolic panel, and endocrinologic evaluation 1
  • Referral to an appropriately trained professional, such as a cardiologist, endocrinologist, mental health professional, or internist, if necessary 1 This approach allows for a systematic evaluation of common causes of fatigue, including anemia, thyroid disorders, nutritional deficiencies, and inflammatory conditions, and addresses lifestyle factors like sleep hygiene, stress management, and physical activity, which are often crucial in managing symptoms.

From the Research

Diagnostic Approach for Fatigue

The diagnostic approach for fatigue involves a comprehensive history and physical examination to guide the workup and diagnosis.

  • A comprehensive history and cardiopulmonary, neurologic, and skin examinations help guide the workup and diagnosis 2.
  • The history and physical examination should focus on identifying common secondary causes (e.g., medications, anemia, pregnancy) and life-threatening problems, such as cancer 3.
  • Fatigue can be classified as physiologic, secondary, or chronic, and the diagnostic approach should take this into account 3, 2.

Laboratory Investigations

Laboratory investigations have a low yield in discovering treatable physical disorders in patients with chronic fatigue.

  • Physical examinations produced diagnostic information in 2% of patients, and laboratory investigations elucidated the cause of fatigue in 5% of patients 4.
  • Results of laboratory studies affect management in only 5 percent of patients, and if initial results are normal, repeat testing is generally not indicated 3.
  • Investigations beyond the history, physical examination, and simple laboratory tests are needed only in the presence of additional symptoms or findings 5.

Special Considerations

Certain conditions, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), require special consideration in the diagnostic approach.

  • ME/CFS is a chronic, severe, and potentially debilitating disorder with demonstrated inflammatory, neurologic, immunologic, and metabolic abnormalities 2.
  • The most important symptom of ME/CFS is postexertional malaise, and exercise can be harmful to patients with ME/CFS because it can trigger postexertional malaise 2.
  • Patients with ME/CFS should be educated about pacing their activity not to exceed their limited energy capacity 2.

Pediatric Considerations

The approach to the child with fatigue requires consideration of age, targeted questions, physical examination clues, and some laboratory first-level tests.

  • Duration, severity, and the age at onset are to be considered when evaluating fatigue in children 6.
  • Specific queries about everyday activities, sleep hygiene, and social domain could be useful in reaching a specific diagnosis and offering an appropriate treatment 6.

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

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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