For a 21-year-old female patient with chronic exertional compartment syndrome, symptoms concerning for restless legs syndrome, iron deficiency, and a mildly elevated lipid profile, do we need to order labs such as Thyroid-Stimulating Hormone or Complete Blood Count?

Laboratory Testing for Suspected Restless Legs Syndrome

Yes, you absolutely need to order specific labs—at minimum, serum ferritin, transferrin saturation, and TSH—as these are essential for both diagnosing secondary causes of RLS and guiding treatment. 1, 2

Essential Laboratory Tests

Iron Studies (Highest Priority)

• Check serum ferritin and transferrin saturation in all patients with clinically significant RLS symptoms, ideally drawn in the morning after avoiding iron-containing supplements for at least 24 hours 1, 2
• Iron supplementation is indicated if ferritin ≤75 ng/mL or transferrin saturation <20%—these thresholds are higher than general population guidelines because brain iron deficiency plays a central role in RLS pathophysiology 1, 3
• Both parameters are required because ferritin alone can be falsely elevated by inflammation, while transferrin saturation <20% indicates functional iron deficiency even when ferritin appears adequate 2

Thyroid Function

• TSH should be obtained as part of the standard endocrine screening for RLS, as thyroid dysfunction can contribute to or mimic RLS symptoms 2

Complete Blood Count

• A CBC is reasonable to obtain to assess for iron-deficiency anemia, which is a well-established secondary cause of RLS and has significantly higher prevalence in affected patients 4, 3
• The CBC complements ferritin/transferrin saturation by identifying overt anemia that may require more aggressive iron repletion 5

Additional Recommended Laboratory Tests

Given this patient's complex presentation (chronic exertional compartment syndrome, iron deficiency, elevated lipids), a comprehensive metabolic panel is warranted:

• Electrolytes and renal function (BUN/creatinine) to identify chronic kidney disease, which is a secondary cause of RLS with increasing prevalence 2
• HbA1c to screen for diabetes mellitus, which has been associated with RLS and can cause peripheral neuropathy that mimics RLS 2
• Calcium as part of baseline metabolic assessment 2

Critical Testing Considerations

Timing and Preparation

• Iron studies must be drawn in the morning with standardized timing because ferritin has diurnal variation 2
• Patients should avoid all iron-containing supplements and foods for at least 24 hours prior to blood draw to prevent falsely elevated results 1, 2

Interpretation Pitfalls

• Do not use general population iron thresholds—RLS requires higher ferritin targets (≤75 ng/mL warrants supplementation vs. the typical <30 ng/mL threshold) because brain iron stores are depleted before serum markers become severely abnormal 1
• Inflammation can raise ferritin independent of true iron stores, which is why transferrin saturation is essential for accurate assessment 2

What NOT to Order

• Polysomnography or periodic limb movement studies are NOT part of routine RLS diagnosis and should be reserved for cases where the diagnosis is uncertain or when assessing treatment response in research settings 2

Clinical Context

This 21-year-old female patient with known iron deficiency already has one of the most common secondary causes of RLS identified 4, 3. The laboratory workup will:

1. Quantify the severity of iron deficiency to guide appropriate repletion strategy (oral vs. IV iron) 1
2. Identify other treatable secondary causes (thyroid dysfunction, renal disease, diabetes) 2
3. Establish baseline values for monitoring treatment response, as iron studies should be rechecked every 6-12 months even after symptom resolution 1

The combination of iron studies, TSH, CBC, and basic metabolic panel provides the essential diagnostic framework for managing this patient's suspected RLS while addressing her known iron deficiency and screening for other contributing factors.