When should a serum ferritin level be ordered in a patient with restless leg syndrome (RLS) or symptoms suggestive of iron deficiency, especially in women of childbearing age or those with a history of gastrointestinal (GI) bleeding, when seen at a sleep clinic?

When to Order Serum Ferritin in Sleep Clinic Patients

Order serum ferritin and transferrin saturation in ALL patients with clinically significant restless legs syndrome (RLS) at initial evaluation, ideally drawn in the morning after avoiding iron-containing supplements for at least 24 hours. 1, 2

Mandatory Testing Protocol

• Check both serum ferritin AND transferrin saturation together in every RLS patient, as ferritin alone can be falsely elevated by inflammation, making transferrin saturation essential to identify functional iron deficiency even when ferritin appears adequate. 2

• Timing matters critically: Draw blood in the morning after the patient has avoided all iron-containing supplements and foods for at least 24 hours, as ferritin has diurnal variation and recent iron intake falsely elevates results. 1, 2

• Use RLS-specific thresholds, not general population cutoffs: Supplement iron if ferritin ≤75 ng/mL OR transferrin saturation <20%, which differs substantially from standard iron deficiency criteria. 1, 3

Clinical Scenarios Requiring Iron Studies

• Any patient meeting diagnostic criteria for RLS (urge to move legs with dysesthesias, worsening at rest, relief with movement, circadian pattern worse in evening/night) should have iron studies checked regardless of symptom severity. 1, 2

• Before initiating any pharmacological treatment for RLS, as correcting iron deficiency may resolve symptoms without need for medications like gabapentin or dopamine agonists. 1, 3

• Women of childbearing age with RLS symptoms warrant particular attention to iron status, as pregnancy is a known secondary cause of RLS and iron supplementation during pregnancy has a favorable safety profile. 3, 2

• Patients with history of gastrointestinal bleeding or known iron deficiency require evaluation for the underlying cause of iron deficiency before initiating iron therapy. 4

Critical Pre-Treatment Screening

• Before prescribing iron supplementation, measure BOTH ferritin and transferrin saturation to exclude hemochromatosis or iron overload states, as case reports document RLS patients with undiagnosed hemochromatosis who developed complications from iron therapy. 4

• Patients with elevated pre-treatment transferrin saturation (>45%) or ferritin (>300 ng/mL) should undergo evaluation for hemochromatosis or other causes of iron overload before receiving iron therapy. 4

Ongoing Monitoring Requirements

• Recheck iron studies every 6-12 months in all RLS patients receiving iron supplementation to monitor response and prevent iron overload. 1, 4

• Reassess iron parameters if RLS symptoms worsen or recur after initial improvement, as symptoms may return if iron stores decline below therapeutic thresholds. 3

Important Caveats About Ferritin Assays

• Different laboratory assays yield substantially different ferritin values: A ferritin of 75 µg/dL measured by Beckman method equals approximately 121 µg/dL by Roche method, meaning clinicians must know which assay their laboratory uses to apply correct treatment thresholds. 5

• Be flexible with cutoff values and use transferrin saturation in conjunction with ferritin, as assay variability may lead to withholding beneficial treatment if rigid cutoffs are applied without considering the specific assay used. 5

When NOT to Order Ferritin

• Do not order polysomnography or periodic limb movement studies as part of routine RLS diagnosis or to determine need for iron supplementation—these are reserved for uncertain diagnoses or research settings. 2

• Do not skip iron studies in patients with "normal" hemoglobin or CBC, as brain iron deficiency in RLS can occur despite normal systemic iron markers, and RLS-specific thresholds (ferritin ≤75 ng/mL) are much higher than anemia thresholds. 1, 6

Special Populations

• End-stage renal disease patients with RLS require different iron parameters: Consider IV iron sucrose if ferritin <200 ng/mL AND transferrin saturation <20%, which are higher thresholds than for general RLS population. 7, 1

• Pediatric RLS patients should receive iron supplementation if ferritin <50 ng/mL, with monitoring for constipation as a common side effect. 1, 3

Treatment Implications of Iron Studies

• Oral iron (ferrous sulfate ≥200 mg elemental iron daily) is first-line for ferritin ≤75 ng/mL or transferrin saturation <20%, though gastrointestinal side effects are common. 3, 8

• IV iron formulations (ferric carboxymaltose, iron dextran, ferumoxytol) should be considered if oral iron fails, is poorly tolerated, or even when ferritin is between 75-100 ng/mL, as IV iron can improve symptoms in this range where oral iron has minimal absorption. 1, 6

• Evidence supports benefit even with "low-normal" ferritin: A randomized controlled trial demonstrated significant IRLS score improvement (9.2 point decrease vs 1.1 with placebo, p=0.01) in RLS patients with baseline ferritin 36-41 ng/mL treated with oral iron for 12 weeks. 8