What is the American Academy of Sleep Medicine (AASM) suggestion for managing Restless Legs Syndrome (RLS) or Periodic Limb Movement Disorder (PLMD) based on ferritin levels?

AASM Management of RLS/PLMD Based on Ferritin Levels

The American Academy of Sleep Medicine recommends iron supplementation in adults with RLS when serum ferritin is ≤75 ng/mL or transferrin saturation is <20%, using oral or IV iron; for ferritin between 75-100 ng/mL, only IV iron should be used; in children, supplement when ferritin is <50 ng/mL. 1

Testing Protocol

• Check serum iron studies (ferritin and transferrin saturation) in all patients with clinically significant RLS or PLMD. 1
• Blood draw should be performed in the morning after avoiding all iron-containing supplements and foods for at least 24 hours. 1
• Transferrin saturation is calculated from iron and total iron binding capacity. 1

Critical caveat: Ferritin assays vary significantly by manufacturer—Roche assays read approximately 60% higher than Beckman assays, meaning a Roche ferritin of 121 ng/mL equals a Beckman value of 75 ng/mL. 2 Clinicians should know which assay their laboratory uses and adjust thresholds accordingly to avoid withholding beneficial treatment. 2

Iron Supplementation Algorithm for Adults

Ferritin ≤75 ng/mL OR Transferrin Saturation <20%

• Use either oral iron (ferrous sulfate) or IV iron formulations. 1, 3
• Oral ferrous sulfate is conditionally recommended with moderate certainty of evidence. 3
• IV ferric carboxymaltose is strongly recommended with moderate certainty of evidence for patients who don't respond to oral therapy. 3
• IV low molecular weight iron dextran and IV ferumoxytol are conditionally recommended. 3

Ferritin 75-100 ng/mL

• Use ONLY IV iron formulations (not oral iron). 1
• This reflects the understanding that brain iron deficiency may persist despite serum ferritin in this range, and IV formulations are more effective at correcting central nervous system iron deficiency. 3

Ferritin >100 ng/mL

• Iron supplementation is generally not indicated based on current consensus guidelines. 1
• However, these thresholds are higher than general population guidelines because brain iron deficiency plays a key role in RLS pathophysiology even when serum iron appears normal. 3

Pediatric Iron Supplementation

• Supplement with oral or IV iron when serum ferritin is <50 ng/mL. 1
• Oral ferrous sulfate is conditionally recommended with very low certainty of evidence in children. 3
• Monitor for constipation, the most common side effect in pediatric patients. 3
• Long-term iron therapy (>2 years) demonstrates sustained improvement in periodic limb movement index and maintenance of adequate ferritin levels. 4

Special Population: End-Stage Renal Disease

• Different thresholds apply: supplement with IV iron sucrose if ferritin <200 ng/mL AND transferrin saturation <20%. 5
• The higher ferritin threshold in ESRD reflects altered iron metabolism and inflammation in advanced kidney disease. 5
• This is a conditional recommendation with moderate certainty of evidence. 5

Monitoring and Duration

• Continue iron supplementation indefinitely with ongoing monitoring, as RLS symptoms may recur if iron stores decline below therapeutic thresholds. 3
• Recheck iron studies every 6-12 months, as brain iron deficiency may persist despite normal serum parameters. 3
• In research studies, oral iron therapy in patients with low-normal ferritin (baseline 36-41 ng/mL) showed significant IRLS score improvement after 12 weeks, with ferritin increases of 25 ng/mL in the treatment group versus 7.5 ng/mL in placebo. 6

Integration with Overall RLS Management

• Iron status assessment and correction should occur BEFORE or concurrent with pharmacological treatment. 3
• Address exacerbating factors (alcohol, caffeine, antihistamines, serotonergic medications, antidopaminergics, untreated OSA) as the first management step. 1
• If pharmacological treatment is needed, alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) are first-line therapy, strongly recommended with moderate certainty of evidence. 3

Common pitfall: Do not assume that "normal" ferritin levels (>50 ng/mL by general medicine standards) are adequate for RLS patients—the threshold of ≤75 ng/mL is specific to sleep disorders and reflects the unique pathophysiology of central iron deficiency in RLS. 3