Laboratory Testing for Restless Legs Syndrome
The essential laboratory workup for RLS should include serum ferritin, electrolytes/renal function, thyroid function (TSH), calcium, HbA1c, and urine albumin-to-creatinine ratio. 1
Core Laboratory Tests
The baseline laboratory evaluation for patients with suspected RLS includes:
Serum ferritin - This is the single most important test, as iron deficiency is a key treatable cause of RLS. Values <50 ng/mL are consistent with RLS and indicate need for iron supplementation 2. The American Geriatrics Society specifically recommends checking ferritin in patients with RLS symptoms 3, 4.
Electrolytes and renal function - Essential to identify chronic kidney disease, which is a secondary cause of RLS with increasing prevalence with age 1, 2.
Thyroid function (TSH) - Part of the standard endocrine screening for RLS 1.
Calcium - Included in baseline metabolic assessment 1.
HbA1c - To screen for diabetes mellitus, which has been associated with RLS 1, 5.
Urine dipstick with albumin-to-creatinine ratio - To assess for renal disease 1.
Clinical Context for Laboratory Testing
Important caveat: RLS is fundamentally a clinical diagnosis based on four essential criteria (urge to move legs, symptoms worse at rest, relief with movement, circadian pattern worsening in evening/night) 4, 5, 6, 7. Laboratory tests do not establish the diagnosis but rather identify secondary causes and guide treatment 4.
Secondary RLS Associations to Screen For:
- Iron deficiency (ferritin <50 ng/mL) - Most critical treatable cause 4, 2
- End-stage renal disease - Identified through creatinine/eGFR 4, 2
- Pregnancy - Clinical history, not laboratory test 4
- Peripheral neuropathy - Requires clinical examination, though metabolic screening (HbA1c, B12) may be indicated 4
Additional Considerations
Blood pressure assessment should be performed as part of the cardiovascular screening, though this is a measurement rather than a laboratory test 1.
Pregnancy test should be obtained where applicable, as pregnancy is a known secondary cause of RLS 1, 4.
Common Pitfall to Avoid:
Do not order polysomnography or periodic limb movement studies as part of routine RLS diagnosis 5, 7. These are not necessary for diagnosis and should be reserved for cases where the diagnosis is uncertain or when assessing treatment response in research settings 1.
The laboratory workup is designed to identify treatable secondary causes (particularly iron deficiency and renal disease) and exclude metabolic/endocrine conditions that may mimic or exacerbate RLS 1, 2. A thorough neurologic examination remains essential to identify arthritis, radiculopathy, or peripheral neuropathy that may present with similar leg discomfort 4.