What lab workup is recommended for a patient presenting with restless leg syndrome?

Laboratory Workup for Restless Leg Syndrome

Serum ferritin testing is the primary laboratory workup recommended for patients presenting with restless leg syndrome, with values less than 50 ng/mL suggesting iron deficiency as a potential cause requiring supplementation. 1

Diagnostic Approach

Before ordering laboratory tests, confirm RLS diagnosis using the established clinical criteria:

1. Urge to move the legs, usually accompanied by uncomfortable sensations
2. Symptoms begin or worsen during periods of rest or inactivity
3. Symptoms partially or totally relieved by movement
4. Symptoms worse in the evening or night
5. Symptoms not solely attributable to another medical condition 1

Recommended Laboratory Tests

Primary Test

• Serum ferritin: The most important laboratory test for RLS 1, 2
  • Values < 50 ng/mL are consistent with iron deficiency contributing to RLS
  • Iron supplementation indicated when ferritin is low

Additional Recommended Tests

• Transferrin saturation: Should be measured alongside ferritin 2
  • Values < 20% indicate iron deficiency requiring treatment
• Complete blood count: To assess for anemia
• Basic metabolic panel: To evaluate renal function (as renal disease is associated with RLS)
• Thyroid function tests: To rule out thyroid disorders 1
• HbA1c: To screen for diabetes 1
• Urine albumin:creatinine ratio: To assess for kidney disease 1

Testing Considerations

When obtaining iron studies:

• Test in the morning
• Patient should avoid iron-containing supplements/foods for at least 24 hours before testing 2
• For patients with chronic kidney disease or end-stage renal disease, different ferritin thresholds may apply 2

Secondary Causes to Consider

Laboratory workup should be guided by clinical suspicion for these common secondary causes of RLS:

• Iron deficiency: Most common treatable cause
• Renal disease: Evaluate renal function
• Diabetes: Check HbA1c
• Pregnancy: Perform pregnancy test when applicable 1
• Peripheral neuropathy: Consider additional neurological testing if suspected

When to Consider Additional Testing

Additional testing may be warranted in specific clinical scenarios:

• Polysomnography: Not routinely needed for diagnosis but may be considered when:
  • Sleep apnea is suspected
  • Diagnosis is uncertain
  • Periodic limb movements during sleep need confirmation 1

Treatment Implications of Laboratory Results

• If ferritin < 50 ng/mL: Iron supplementation is indicated 1, 2
• If ferritin ≤ 75 ng/mL or transferrin saturation < 20% in adults: Oral or IV iron supplementation recommended 2
• If ferritin between 75-100 ng/mL: IV iron only may be considered 2

Common Pitfalls to Avoid

• Overlooking iron studies: Iron deficiency is a major treatable cause of RLS but is frequently overlooked 2
• Failing to consider medications: Certain medications can exacerbate RLS symptoms, including tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists 1
• Missing secondary causes: Always evaluate for common conditions associated with RLS, including renal disease, diabetes, and pregnancy
• Inadequate follow-up: Regular monitoring of iron status is necessary, especially in chronic RLS

The laboratory workup for RLS should be focused and guided by the understanding that iron deficiency is a major treatable cause, while also screening for other common secondary causes that may require specific management approaches.