What are the target serum ferritin levels for a patient with restless leg syndrome?

Iron Parameter Goals for Restless Legs Syndrome

For patients with RLS, target serum ferritin levels of >75 ng/mL and transferrin saturation ≥20%, with iron supplementation initiated when ferritin is ≤75 ng/mL or transferrin saturation is <20%. 1, 2

Specific Iron Thresholds for Treatment Decisions

Adults with RLS

• Initiate oral OR intravenous iron supplementation when serum ferritin ≤75 ng/mL or transferrin saturation <20% 1, 2
• Use ONLY intravenous iron (not oral) when serum ferritin is between 75-100 ng/mL, as oral iron absorption is poor in this range 1, 3
• Iron supplementation is generally not indicated when ferritin >100 ng/mL based on current evidence 3

Children with RLS

• Initiate iron supplementation when serum ferritin <50 ng/mL using oral or IV formulations 1, 3

Special Population: End-Stage Renal Disease

• Use IV iron sucrose when ferritin <200 ng/mL AND transferrin saturation <20% (conditional recommendation, moderate certainty) 1

Critical Testing Requirements

Obtain iron studies in the morning after avoiding all iron-containing supplements and foods for at least 24 hours prior to blood draw to ensure accurate measurements 1, 2. The required tests include:

• Serum ferritin 1, 2
• Transferrin saturation (or total iron binding capacity) 1

Important Caveats About Ferritin Measurement

Different laboratory assays yield significantly different ferritin values, which has critical implications for treatment decisions 4. The Roche method produces values approximately 60% higher than the Beckman method at clinically relevant cutoffs 4. For example:

• A Beckman ferritin of 50 ng/mL equals approximately 83 ng/mL on Roche 4
• A Beckman ferritin of 75 ng/mL equals approximately 121 ng/mL on Roche 4

Clinicians should be flexible with ferritin cutoffs and also use transferrin saturation percentage to guide treatment decisions, given assay variability and the limited data underlying current recommendations 4.

Rationale: Why Higher Ferritin Targets for RLS

These RLS-specific iron thresholds are substantially higher than general population cutoffs for iron deficiency (<15-30 ng/mL) because brain iron deficiency plays a critical role in RLS pathophysiology even when serum iron appears normal 2, 3. The impairment of dopamine transport in the substantia nigra due to reduced intracellular iron is central to RLS pathogenesis 1.

Values less than 50 ng/mL are consistent with a diagnosis of RLS and suggest the need for iron supplementation 1. However, more recent evidence supports the higher threshold of ≤75 ng/mL 1, 2.

Monitoring During Treatment

Re-measure serum iron parameters once or twice yearly during ongoing iron therapy 5. This is essential because:

• RLS symptoms may recur if iron stores decline below therapeutic thresholds 2
• Brain iron deficiency may persist despite normal serum parameters 2
• Monitoring prevents iron overload in susceptible individuals 5

Before initiating iron therapy, measure serum transferrin saturation and ferritin to screen for hemochromatosis or iron overload, particularly in patients of northern European ancestry 5. Patients with elevated pre-treatment transferrin saturation or serum ferritin should undergo evaluation to determine the cause before iron treatment 5.

Additional Considerations for Inflammatory Conditions

In patients with acute or chronic inflammatory conditions (including chronic kidney disease), ferritin levels may be falsely elevated 6. In these populations, a ferritin cutoff of <70 ng/mL may be more appropriate for identifying iron deficiency contributing to RLS 6.

Clinical Significance of Iron Repletion

Low serum ferritin is associated with both RLS symptom severity and augmentation risk in patients treated with dopaminergic agents 7. Iron supplementation not only relieves fundamental RLS symptoms but also lowers the risk of augmentation—a paradoxical worsening of symptoms with dopaminergic therapy 7.