Laboratory Tests for Restless Legs Syndrome
Ferritin level is the priority laboratory test for patients with restless legs syndrome (RLS), with additional testing including complete blood count, basic metabolic panel, liver function tests, and thyroid function tests to rule out secondary causes. 1
Essential Laboratory Tests
Ferritin level:
Iron studies:
- Transferrin saturation
- Serum iron
- Total iron binding capacity (TIBC)
Complete blood count (CBC):
- To evaluate for anemia and other hematologic abnormalities 1
Basic metabolic panel:
- To assess kidney function and electrolyte balance 1
- Particularly important as kidney disease is associated with RLS
Liver function tests:
- To rule out liver disorders that may contribute to RLS 1
Thyroid function tests:
- TSH, free T4 to evaluate for thyroid dysfunction 1
HbA1c:
- To screen for diabetes, which can cause peripheral neuropathy 1
Urine albumin:creatinine ratio:
- To assess for kidney damage 1
Additional Testing Based on Clinical Presentation
For patients with suspected peripheral nerve involvement:
- Electromyography with peripheral nerve neurophysiological tests 2
- Consider histological peripheral nerve examination in select cases 2
For suspected central nervous system involvement:
- Detailed neurological examination 2
- Consider neuroimaging (MRI) in cases with suspected CNS vasculitic/vasculopathic alterations 2
Clinical Pearls and Pitfalls
Important caveat: Normal ferritin levels do not rule out iron deficiency in RLS. Some patients may have iron deficiency with normal ferritin levels 3. Consider bone marrow examination in equivocal cases with strong clinical suspicion.
Risk of hemochromatosis: Always check serum transferrin saturation and ferritin levels before initiating iron therapy for RLS 4. Patients with elevated pre-treatment transferrin saturation or serum ferritin levels should be evaluated for hemochromatosis before iron supplementation.
Monitoring: For patients on iron therapy, serum iron parameters should be re-measured once or twice yearly 4.
Augmentation risk: Low serum ferritin levels are associated with augmentation of RLS symptoms in patients taking dopaminergic medications 5. Regular monitoring of iron status is essential for patients on dopaminergic agents.
Special Considerations
In patients with diabetes, comprehensive foot examination should include assessment for peripheral neuropathy which may contribute to RLS symptoms 2.
For patients with HCV infection, consider evaluation for peripheral neuropathy which may manifest as RLS 2.
In young adults, the relationship between serum iron stores and RLS may be less clear 6, but iron studies should still be performed as part of the diagnostic workup.
By systematically evaluating these laboratory parameters, clinicians can identify treatable causes of RLS and guide appropriate management strategies.