In a 68-year-old man with insomnia due to restless‑legs syndrome and a history of atrial fibrillation, GERD, celiac disease, type 2 diabetes mellitus, hypertension, and BMI 28, which test should be ordered now: iron panel, electromyography, nerve conduction study, or polysomnography?

Order an Iron Panel Now

You should order an iron panel (option a) immediately, measuring serum ferritin and transferrin saturation after a 24-hour avoidance of iron-containing supplements or foods. 1 This patient presents with classic restless legs syndrome (RLS), and iron deficiency assessment is the essential first diagnostic step before initiating any pharmacologic therapy.

Clinical Reasoning for Iron Panel Priority

Why Iron Studies Are Mandatory First-Line Testing

• Brain iron deficiency is a core pathophysiologic mechanism of RLS, and routine screening of iron indices is an essential component of RLS patient care before any treatment decisions. 1
• The 2025 American Academy of Sleep Medicine guideline issues a strong recommendation to check serum ferritin and transferrin saturation in all RLS patients, as iron repletion can resolve symptoms without chronic pharmacotherapy. 1, 2
• Iron supplementation thresholds for RLS differ from general population standards: treatment should be initiated when ferritin ≤ 100 ng/mL or transferrin saturation < 20%, which are higher cut-offs than typical anemia thresholds. 1, 2
• This patient has celiac disease, a condition strongly associated with iron malabsorption and deficiency, making iron assessment even more critical. 3

Why the Other Tests Are Not Indicated Now

• Electromyography and nerve conduction studies (options b & c) are not part of RLS diagnostic evaluation. 4 RLS is diagnosed clinically using the five essential IRLSSG criteria, which this patient clearly meets: urge to move legs with uncomfortable sensations, worsening at rest, relief with movement, evening/nighttime predominance, and symptoms causing sleep disturbance. 4
• While this patient has increased pinprick pain suggesting diabetic peripheral neuropathy, the sensory symptoms described (urge to move, relief with movement, circadian pattern) are characteristic of RLS, not neuropathy alone. 3 Neuropathy can coexist with or trigger RLS (21.5% prevalence in peripheral neuropathy patients), but electrodiagnostic studies do not diagnose RLS. 3
• Polysomnography (option d) is not recommended for RLS diagnosis. 4, 3 The diagnosis is made by clinical history using the essential criteria. Polysomnography may detect periodic leg movements but is reserved for cases where the diagnosis is uncertain or when evaluating for comorbid sleep disorders like obstructive sleep apnea. 4

Critical Next Steps After Iron Panel Results

If Iron Deficiency Is Confirmed (Ferritin ≤ 100 ng/mL or TSAT < 20%)

• Intravenous ferric carboxymaltose 1000 mg receives a strong recommendation as the preferred iron formulation, with multiple recent RCTs demonstrating superior efficacy. 1
• Oral ferrous sulfate 325–650 mg daily or every other day is a conditional alternative when IV access is limited or patient preference dictates. 1
• Iron repletion alone may eliminate the need for chronic pharmacologic therapy. 1, 2

If Iron Stores Are Adequate

• Discontinue any RLS-exacerbating medications before starting pharmacotherapy. This patient takes amlodipine, which is not known to worsen RLS, but review for any unreported antidepressants, antihistamines, or dopamine antagonists. 1, 2
• Gabapentinoids (gabapentin enacarbil, gabapentin, or pregabalin) are first-line pharmacologic therapy with strong recommendations and moderate certainty of benefit. 1, 2 Approximately 70% of patients treated with gabapentinoids achieve much or very much improved symptoms versus 40% with placebo. 3

Major Shift Away from Dopamine Agonists

• The 2025 AASM guideline issues a conditional recommendation against routine use of dopamine agonists (pramipexole, ropinirole, rotigotine) due to a 7–10% annual risk of augmentation—an iatrogenic worsening of RLS symptoms that escalates with treatment duration. 1, 2
• Dopamine agonists should be reserved only for short-term use when patients explicitly accept augmentation risk and prioritize rapid symptom relief over long-term safety. 1, 2
• Cabergoline receives a strong recommendation against use due to cardiac valvulopathy risk. 1

Special Considerations for This Patient's Comorbidities

Celiac Disease and Iron Absorption

• Celiac disease impairs gastrointestinal iron absorption even with dietary adherence, making IV iron potentially more effective than oral supplementation if deficiency is confirmed. 1
• The patient's recent normal EGD suggests adequate mucosal healing, but iron stores may still be depleted from years of malabsorption. 3

Type 2 Diabetes and Peripheral Neuropathy

• The increased pinprick pain below the knees indicates small fiber neuropathy, which can coexist with RLS (21.5% prevalence in peripheral neuropathy). 3, 5
• Gabapentinoids are particularly advantageous in this patient because they treat both RLS and neuropathic pain. 1

Atrial Fibrillation and Cardiovascular Risk

• RLS is associated with elevated cardiovascular disease rates (29.6% with coronary artery disease, stroke, or heart failure), and treating RLS reduces future cardiovascular risk. 3, 6
• Apixaban does not exacerbate RLS and should be continued. 1

Common Pitfalls to Avoid

• Do not initiate gabapentinoids or dopamine agonists before checking iron studies—correcting iron deficiency may eliminate the need for chronic medication. 1, 2
• Do not order polysomnography for RLS diagnosis—this patient meets all five essential clinical criteria, making the diagnosis straightforward. 4, 3
• Do not prescribe dopamine agonists as first-line therapy—the augmentation risk now outweighs short-term efficacy benefits. 1, 2
• Do not overlook celiac disease as a cause of persistent iron deficiency—even with dietary adherence, malabsorption may require IV iron for adequate repletion. 1