What is the best course of treatment for a 21-year-old female with a history of chronic exertional compartment syndrome (CECS) versus shin splints, presenting with symptoms concerning for restless legs syndrome (RLS), iron deficiency (low iron 34, total iron-binding capacity (TIBC) 419, transferrin saturation (TSAT) 8%, unsaturated iron-binding capacity (UIBC) 384), and mildly elevated lipid profile (hypercholesterolemia, high-density lipoprotein (HDL) 110, low-density lipoprotein (LDL) 104, triglycerides 44)?

Iron Deficiency with Restless Legs Syndrome: Immediate Treatment Indicated

You should start iron supplementation immediately—this patient has severe iron deficiency (TSAT 8%) that meets treatment thresholds for RLS, and iron therapy is the appropriate first-line intervention before considering any pharmacological agents. 1, 2

Lab Interpretation

Your patient's iron studies reveal significant iron deficiency that is likely driving her RLS symptoms:

• Transferrin saturation (TSAT) of 8% is well below the 20% threshold for RLS treatment 1, 2
• TIBC of 419 (elevated) and UIBC of 384 (elevated) confirm iron deficiency state 2
• Serum iron of 34 is low, consistent with depleted iron stores 2
• The lipid panel (total cholesterol 223, HDL 110, LDL 104, TG 44) is actually favorable and requires no intervention—the HDL is excellent and LDL is optimal 1

The pathophysiology here is critical: brain iron deficiency in the substantia nigra impairs dopamine transport and synthesis, which is the primary mechanism producing RLS symptoms, even when peripheral iron stores appear borderline. 3, 4

Follow-Up Labs Needed

Order a morning fasting ferritin level immediately (avoiding iron supplements for at least 24 hours before the blood draw). 1, 2 This is essential because:

• The American Academy of Sleep Medicine recommends iron supplementation when ferritin ≤75 ng/mL OR transferrin saturation <20% 1, 2
• Your patient already meets the TSAT criterion (<20%), but ferritin will guide the intensity and route of iron therapy 1, 2
• RLS-specific thresholds for iron deficiency are higher than general population guidelines (ferritin ≤75 ng/mL vs. the typical <30 ng/mL cutoff) 1, 3

Screen for hemochromatosis before starting iron therapy by checking the ferritin level you're already ordering—if it's paradoxically elevated despite low TSAT, consider HFE gene testing, as iron therapy can unmask hemochromatosis. 5

Monitor iron parameters every 6-12 months during treatment to ensure adequate repletion and avoid iron overload. 1, 5

Treatment Plan: Start Now, Don't Wait

Immediate Iron Supplementation

Begin oral ferrous sulfate at least 200 mg of elemental iron daily (this typically means 325 mg ferrous sulfate tablets, which contain 65 mg elemental iron, taken 3 times daily). 2, 6

• Take iron on an empty stomach if tolerated, or with food if gastrointestinal side effects occur 2
• Warn the patient about constipation, the most common side effect, and recommend stool softeners prophylactically 2
• Continue for at least 3 months before reassessing, as brain iron repletion lags behind peripheral stores 1, 2

When to Consider IV Iron

If oral iron is ineffective after 6-12 weeks, poorly tolerated, or if ferritin comes back between 75-100 ng/mL, strongly consider IV ferric carboxymaltose. 1, 2 IV iron formulations may be more effective than oral iron for RLS, particularly when ferritin is in this intermediate range. 3, 2

The American Academy of Sleep Medicine gives IV ferric carboxymaltose a strong recommendation with moderate certainty for patients with appropriate iron parameters who don't respond to oral therapy. 1

Address Exacerbating Factors

Eliminate or reduce the following immediately, as they worsen RLS symptoms: 1

• Caffeine, especially within 6 hours of bedtime 1
• Alcohol, particularly in the evening 1
• Antihistamines (diphenhydramine, doxylamine in sleep aids) 1
• SSRIs or other serotonergic medications if she's taking any 1
• Antipsychotics or dopamine antagonists (including metoclopramide for nausea) 1

Pharmacological Treatment: Only If Iron Fails

Do not start gabapentin, pregabalin, or any other RLS medication yet. 1, 2 The treatment algorithm is clear:

1. First, correct iron deficiency (you are here) 1, 2
2. Second, if symptoms persist after 3 months of adequate iron repletion, then consider alpha-2-delta ligands (gabapentin 1800-2400 mg/day divided three times daily, gabapentin enacarbil, or pregabalin) as first-line pharmacological therapy 1
3. Never use dopamine agonists (ropinirole, pramipexole, rotigotine) as first-line therapy due to high risk of augmentation—a paradoxical worsening of symptoms with long-term use 1, 7

Critical Pitfalls to Avoid

Do not assume this is "just shin splints" or CECS causing her leg symptoms. RLS has specific diagnostic criteria: urge to move the legs with uncomfortable sensations that worsen at rest, improve with movement, and follow a circadian pattern (worse at night). 8, 1 If her symptoms fit this pattern, treat the RLS.

Do not wait for ferritin results to start oral iron. Her TSAT of 8% alone justifies immediate treatment. 1, 2

Do not use dopamine agonists like ropinirole or pramipexole in a 21-year-old. These medications cause augmentation in up to 60% of patients with long-term use, leading to earlier symptom onset, increased intensity, and spread to other body parts. 1, 7 The FDA label shows efficacy, but current guidelines explicitly recommend against their standard use. 1, 7

Do not ignore the lipid panel—it's actually excellent. An HDL of 110 is protective, LDL of 104 is optimal, and triglycerides of 44 are excellent. No statin or other lipid therapy is indicated. 1

Expected Timeline

• Weeks 2-4: Peripheral iron stores begin to improve, but RLS symptoms may not yet change 2
• Weeks 6-12: Brain iron repletion occurs, and RLS symptoms should begin to improve 2, 9, 6
• 3 months: Reassess with repeat iron studies and RLS symptom severity 1, 2
• If no improvement by 3 months: Consider IV iron or add alpha-2-delta ligand therapy 1, 2