What laboratory tests should be ordered for a patient presenting with low energy and fatigue?

Laboratory Tests for Fatigue Evaluation

For patients presenting with low energy and fatigue, a comprehensive laboratory evaluation should include complete blood count (CBC), comprehensive metabolic panel (CMP), thyroid function tests (TSH and free T4), iron studies (iron, ferritin, transferrin, transferrin saturation), inflammatory markers (ESR, CRP), vitamin D level, and urinalysis as the initial diagnostic workup. 1

Initial Laboratory Evaluation

First-line Tests

• Complete Blood Count (CBC) with differential

  • Evaluates for anemia, infection, and other hematologic abnormalities 1
  • Abnormalities may indicate underlying causes of fatigue

• Comprehensive Metabolic Panel (CMP)

  • Includes electrolytes, BUN, creatinine, liver function tests, and glucose/HbA1c
  • Screens for metabolic abnormalities, liver dysfunction, kidney disease, and diabetes 1

• Thyroid Function Tests

  • TSH is the primary screening test
  • Free T4 should be added if TSH is abnormal 1
  • Hypothyroidism commonly presents with fatigue, weight gain, cold intolerance, and constipation 2

• Iron Studies

  • Include plasma iron, transferrin, transferrin saturation, and ferritin 1
  • Iron deficiency can cause fatigue even without anemia 1

• Inflammatory Markers

  • ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein)
  • Help identify inflammatory or autoimmune conditions 1

• Vitamin D Level

  • Deficiency can contribute to fatigue 1

• Urinalysis

  • Screens for infection, kidney disease, and diabetes 1

Second-line Tests (Based on Initial Findings and Clinical Suspicion)

• Hormone Testing

  • Morning cortisol and ACTH if adrenal insufficiency is suspected 2
  • Gonadal hormones (testosterone in men, estradiol in women, FSH, LH) if hypogonadism is suspected 2

• Autoimmune Markers

  • Consider if rheumatologic disease is suspected 1

• Cardiac Evaluation

  • BNP or NT-proBNP if heart failure is suspected 1
  • Consider ECG and chest radiograph for patients with suspected cardiac-related fatigue 1

• Lipid Profile

  • To assess for dyslipidemia 1

Special Considerations

Endocrine Disorders

• For suspected hypophysitis or central endocrine disorders, conduct morning tests (around 8 am) of thyroid function, adrenal function, and gonadal hormones 2
• Consider MRI of the sella with pituitary cuts if central endocrine disorder is suspected 2

Cardiac Causes

• For suspected cardiac-related fatigue, include BNP/NT-proBNP, electrolytes (including calcium and magnesium), and renal function tests 1

Important Caveats and Pitfalls

• Normal laboratory values do not exclude fatigue-causing conditions - Consider expanded testing when symptoms persist despite normal initial workup 1

• Presence of an abnormal laboratory result does not necessarily indicate the cause of fatigue - Abnormal results should be interpreted in clinical context 3, 4

• Low diagnostic yield of extensive testing - Studies have shown that physical examinations and laboratory investigations have relatively low yield (2-5%) in identifying organic causes of chronic fatigue 4

• Consider psychological causes - Psychological factors are common contributors to fatigue and should be assessed alongside physical causes 3

• Energy and fatigue may be independent states - Research suggests that energy and fatigue might be distinct perceptual states rather than opposites on a single continuum 5

• Avoid excessive testing - Focus on targeted testing based on clinical presentation rather than ordering extensive panels without clear indications 4

By following this structured approach to laboratory evaluation, clinicians can efficiently identify potential causes of fatigue while avoiding unnecessary testing, ultimately improving patient outcomes and quality of life.