What labs should be checked in patients presenting with severe restless legs syndrome?

Laboratory Testing for Severe Restless Legs Syndrome

Ferritin level is the priority laboratory test for patients with severe restless legs syndrome (RLS), with values less than 50 ng/mL indicating a need for iron supplementation. 1

Essential Laboratory Tests for RLS Evaluation

When evaluating patients with severe restless legs syndrome, the following laboratory tests should be ordered:

1. Iron Studies:

   • Serum ferritin (primary test)
   • Transferrin saturation
   • Total iron binding capacity (TIBC)
   • Serum iron

2. Complete Blood Count (CBC):

   • To assess for anemia and other hematologic abnormalities

3. Basic Metabolic Panel:

   • To evaluate kidney function and electrolyte balance
   • Particularly important as renal failure is a common secondary cause of RLS 1

4. Additional Tests:

   • Liver function tests
   • Thyroid function tests (TSH, free T4)
   • HbA1c (to screen for diabetes)
   • Urine albumin:creatinine ratio 1

Importance of Iron Studies in RLS

Iron deficiency plays a crucial role in RLS pathophysiology, with reduced CNS iron stores being a consistent finding even in idiopathic cases 2. The relationship between iron and RLS is supported by several observations:

• Low ferritin levels (<50 ng/mL) are consistent with a diagnosis of RLS 1
• Iron supplementation can be efficacious as initial treatment in patients with low-normal serum iron indices 3
• CNS pathology of RLS demonstrates reduced iron stores, suggesting altered homeostatic control of iron 2

Secondary Causes Requiring Laboratory Investigation

Several medical conditions can cause or exacerbate RLS, necessitating specific laboratory testing:

• Chronic kidney disease: Evaluate with BUN, creatinine, eGFR
• Pregnancy: Consider pregnancy testing in women of childbearing age
• Neuropathy: Consider glucose testing, vitamin B12 levels
• Medication-induced RLS: Review medications, particularly antidepressants and antihistamines 3

Clinical Pearls and Pitfalls

• Ferritin threshold: While many labs consider ferritin >20 ng/mL as normal, RLS patients may benefit from iron supplementation with ferritin levels <50 ng/mL 1
• ESRD patients: In end-stage renal disease patients, consider IV iron sucrose when ferritin <200 ng/mL and transferrin saturation <20% 1
• Augmentation monitoring: For patients on dopaminergic medications, regular monitoring is essential to detect augmentation (worsening of symptoms with long-term treatment) 1, 3
• Diagnostic confirmation: Laboratory tests help rule out secondary causes but don't confirm RLS diagnosis, which remains clinical based on the four essential criteria 4, 1

Follow-up Testing

After initial evaluation and treatment initiation:

• Monitor ferritin levels periodically, especially in patients receiving iron supplementation
• For patients on dopaminergic agents, regular follow-up is necessary to assess for augmentation 1, 5
• In patients with renal impairment, more frequent monitoring of renal function may be necessary when using certain medications like gabapentin 1

By systematically evaluating these laboratory parameters, clinicians can identify treatable causes of RLS and optimize management strategies for patients with severe symptoms.