What initial laboratory tests are recommended for a patient presenting with weakness and fatigue?

Initial Laboratory Tests for Patients with Weakness and Fatigue

For patients presenting with weakness and fatigue, initial laboratory evaluation should include complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and urinalysis. 1

Recommended Initial Laboratory Workup

Core Laboratory Tests

• Complete blood count (CBC) with differential 1

  • Evaluates for anemia, infection, and other hematologic abnormalities
  • Compare current hemoglobin/hematocrit with previous values if available

• Comprehensive metabolic panel 1

  • Assesses electrolytes (including calcium and magnesium)
  • Evaluates hepatic and renal function
  • Blood urea nitrogen and serum creatinine

• Thyroid-stimulating hormone (TSH) 1

  • Essential for detecting hypothyroidism or hyperthyroidism

• Urinalysis 1

  • Screens for renal disease, infection, and dehydration

Additional First-Line Tests

• Fasting blood glucose or glycohemoglobin 1

  • Evaluates for diabetes or glucose abnormalities

• Lipid profile 1

  • Important for cardiovascular risk assessment

Evaluation Algorithm Based on Clinical Context

For Patients with Moderate to Severe Fatigue

1. Perform the core laboratory tests listed above
2. Assess for treatable contributing factors:
   • Anemia
   • Electrolyte abnormalities
   • Renal or hepatic dysfunction
   • Endocrine disorders (especially thyroid dysfunction)
   • Sleep disturbances
   • Pain
   • Emotional distress 1

For Patients with Suspected Heart Failure

When weakness and fatigue are accompanied by dyspnea, orthopnea, or edema:

• Add 12-lead electrocardiogram and chest radiograph (PA and lateral) 1
• Consider echocardiography to assess left ventricular function 1
• Assess orthostatic blood pressure changes 1, 2

For Cancer Survivors

• Compare current hemoglobin/hematocrit with end-of-treatment values
• Consider more comprehensive endocrinologic evaluation if other symptoms are present 1

Clinical Pearls and Pitfalls

• Avoid excessive testing: Studies show that extensive laboratory investigations in patients with chronic fatigue have a low diagnostic yield (only about 5%) 3, 4. Focus on the core tests first.

• Don't miss endocrine disorders: Thyroid dysfunction is a common treatable cause of fatigue and should always be evaluated.

• Consider psychiatric causes: Psychological factors often contribute to fatigue and should be assessed if medical causes are not identified 4.

• Watch for rare but serious conditions: Occasionally, fatigue may be the presenting symptom of rare conditions such as mitochondrial myopathies 5 or acid maltase deficiency 6, particularly when accompanied by muscle weakness and respiratory symptoms.

• Reassess periodically: If initial testing is unrevealing but symptoms persist, consider periodic reassessment rather than extensive "fishing expeditions" for diagnoses 7.

By following this structured approach to laboratory testing for weakness and fatigue, clinicians can efficiently identify treatable causes while avoiding unnecessary testing.