What laboratory tests are recommended for Restless Legs Syndrome (RLS)?

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From the Guidelines

To diagnose and manage Restless Legs Syndrome (RLS), clinicians should regularly test serum iron studies, including ferritin and transferrin saturation, as these are crucial in determining the need for oral or intravenous iron treatment. According to the American Academy of Sleep Medicine clinical practice guideline 1, testing should ideally be administered in the morning, avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw. The key laboratory tests to consider are:

  • Serum ferritin
  • Transferrin saturation (calculated from iron and total iron binding capacity) These tests are essential because iron deficiency is strongly associated with RLS symptoms, and supplementation guidelines differ from those for the general population. For adults with RLS, iron supplementation should be instituted with oral or IV iron if serum ferritin ≤ 75 ng/mL or transferrin saturation < 20% 1. In children, supplementation of iron should be instituted for serum ferritin < 50 ng/mL with oral or IV formulations 1.

When evaluating patients with RLS, it is also important to consider other potential exacerbating factors, such as:

  • Alcohol
  • Caffeine
  • Antihistaminergic, serotonergic, antidopaminergic medications
  • Untreated obstructive sleep apnea Addressing these factors is crucial in the management of RLS, as they can significantly impact symptoms and treatment outcomes 1.

By prioritizing serum iron studies and addressing exacerbating factors, clinicians can develop an effective treatment plan for patients with RLS, which may include iron supplementation, lifestyle modifications, and other therapies as needed.

From the Research

Laboratory Tests for Restless Legs Syndrome (RLS)

To diagnose and manage RLS, several laboratory tests can be used to identify underlying causes and guide treatment. The following tests are recommended:

  • Iron measures, including:
    • Ferritin levels: to assess iron stores 2, 3, 4
    • Transferrin saturation: to evaluate iron deficiency 2
  • Kidney function tests:
    • Estimated glomerular filtration rate (eGFR): to assess chronic kidney disease (CKD) 3
  • Other tests:
    • Complete blood count (CBC): to rule out other conditions that may cause similar symptoms
    • Blood chemistry tests: to evaluate for other underlying conditions, such as diabetes or thyroid disorders

Interpretation of Laboratory Results

When interpreting laboratory results, the following should be considered:

  • Ferritin levels less than 40-50 ng/ml may indicate iron deficiency 3, 4
  • Ferritin levels less than 70 ng/ml may be associated with RLS in patients with inflammatory conditions 3
  • eGFR values and stages of CKD should be reported to assess the risk of RLS 3

Special Considerations

In some cases, additional tests may be necessary, such as:

  • Bone marrow examination: to confirm iron deficiency when ferritin levels are equivocal 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Restless Legs Syndrome: Contemporary Diagnosis and Treatment.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

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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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