What is included in the usual laboratory workup for restless leg syndrome?

Laboratory Workup for Restless Leg Syndrome

Serum ferritin testing is the primary laboratory investigation recommended for all patients with suspected restless leg syndrome (RLS), with additional tests including thyroid function, HbA1c, and renal function to rule out secondary causes. 1

Essential Laboratory Tests

• Serum ferritin: Most important test for RLS evaluation

  • Values < 50 ng/mL suggest iron deficiency requiring supplementation
  • Should be tested in the morning
  • Patients should avoid iron supplements/foods for 24 hours before testing 1

• Iron studies:

  • Transferrin saturation (< 20% indicates deficiency)
  • Total iron binding capacity 1

• Tests to rule out secondary causes:

  • Thyroid function tests (TSH, free T4)
  • HbA1c for diabetes screening
  • Renal function tests (creatinine, BUN)
  • Urine albumin:creatinine ratio 1

Additional Testing Based on Clinical Suspicion

• Complete blood count: To evaluate for anemia or other hematologic conditions 2

• Basic metabolic panel: To assess electrolytes and kidney function 2

• Liver function tests: To rule out hepatic causes of secondary RLS 2

• Pregnancy test: When applicable, as pregnancy can trigger or worsen RLS 1

Special Considerations

• Iron deficiency is strongly associated with RLS pathophysiology, even without anemia 3
• Regular monitoring of iron status is important for RLS management, particularly in patients on dopaminergic medications to reduce augmentation risk 1
• Polysomnography is not routinely required for RLS diagnosis but may be considered when:
  • Sleep apnea is suspected
  • Diagnosis is uncertain
  • Confirmation of periodic limb movements during sleep is needed 1

Diagnostic Approach

1. First step: Confirm clinical diagnosis using established criteria (urge to move legs, worsening with rest, improvement with movement, evening/night exacerbation)
2. Second step: Order serum ferritin and transferrin saturation as primary laboratory tests
3. Third step: Order additional tests to rule out secondary causes (thyroid, diabetes, kidney disease)
4. Fourth step: Consider polysomnography only in specific clinical scenarios

Common Pitfalls to Avoid

• Failing to check iron status in all RLS patients, even those without anemia
• Not considering secondary causes of RLS (renal disease, diabetes, pregnancy)
• Over-reliance on polysomnography for diagnosis when RLS is primarily a clinical diagnosis
• Missing the opportunity to identify and treat iron deficiency, which can significantly improve symptoms 3

Iron deficiency must be identified and treated not only to improve RLS symptoms but also to potentially lower the risk of augmentation when dopaminergic medications are used 1.