Iron Studies for Restless Legs Syndrome: Ferritin Plus Transferrin Saturation Required
You must order both serum ferritin AND transferrin saturation together—ferritin alone is insufficient for RLS evaluation. 1
Why Both Tests Are Essential
The American Academy of Sleep Medicine mandates checking both serum ferritin and transferrin saturation in all patients with clinically significant RLS because these parameters serve different but complementary diagnostic purposes. 1
Ferritin Limitations Require Transferrin Saturation
Ferritin can be falsely elevated by inflammation, making it an unreliable sole indicator of iron status in RLS patients who may have concurrent inflammatory conditions. 1
Transferrin saturation <20% identifies functional iron deficiency even when ferritin appears adequate, revealing patients who need iron supplementation despite seemingly normal ferritin levels. 1
Both parameters together provide the complete picture needed to determine appropriate iron therapy (oral versus IV formulations). 1
RLS-Specific Treatment Thresholds Require Both Values
The treatment algorithm depends on having both measurements:
- Oral OR IV iron indicated: ferritin ≤75 ng/mL OR transferrin saturation <20% 1
- IV iron only (not oral): ferritin 75-100 ng/mL 1
- No iron supplementation: ferritin >100 ng/mL with adequate transferrin saturation 1
Proper Testing Protocol
Timing and Preparation Requirements
Draw blood in the morning after the patient has avoided all iron-containing supplements and foods for at least 24 hours prior to the blood draw. 1
Morning timing is critical because ferritin has diurnal variation, and recent iron intake can falsely elevate results. 2
Complete Iron Panel Components
The full iron studies should include:
- Serum ferritin 1
- Transferrin saturation (calculated from serum iron and total iron binding capacity) 1
Critical Assay Variation Pitfall
Different laboratory assays produce significantly different ferritin values for the same sample, which can affect treatment decisions. 2
- The Roche method yields ferritin values approximately 60% higher than the Beckman method for the same sample. 2
- A ferritin of 75 μg/dL on Beckman equals approximately 121 μg/dL on Roche. 2
- This makes transferrin saturation even more critical as a complementary parameter that is less affected by assay variation. 2
Why This Matters for RLS Pathophysiology
CSF studies demonstrate that RLS patients have reduced ferritin and elevated transferrin in cerebrospinal fluid, indicating brain iron deficiency despite normal serum parameters. 3
This CNS iron deficiency explains why RLS requires higher ferritin thresholds (≤75 ng/mL) than the general population (<15-30 ng/mL). 1
Transferrin saturation <20% indicates inadequate iron delivery to tissues including the brain, regardless of ferritin level. 1
Additional Screening Considerations
While not part of "iron studies" per se, consider these concurrent tests in RLS evaluation:
Renal function (creatinine, eGFR) to identify chronic kidney disease, which requires different RLS treatment algorithms. 1, 4
CBC to assess for overt anemia requiring more aggressive iron repletion. 5
Celiac disease screening (tissue transglutaminase antibodies) in patients with unexplained low ferritin, as celiac disease is a common cause of iron deficiency in RLS. 6