In a 65-year-old female with hypertension, type 2 diabetes mellitus, and atrial fibrillation who is taking metformin and a statin, and who presents with worsening insomnia and a restless‑legs sensation at rest and at night, with normal vital signs, unremarkable physical examination, and normal complete blood count, what evaluation should be recommended for her symptoms?

Evaluation for Restless Legs Syndrome

Check serum ferritin and transferrin saturation immediately—this patient has classic restless legs syndrome (RLS), and iron deficiency is the most important treatable cause to identify before considering any pharmacologic therapy.

Clinical Recognition

This patient presents with textbook RLS symptoms 1:

• Urge to move legs at rest and night
• Worsening insomnia
• Relief with movement (implied by "urge to move")
• Evening/nocturnal predominance

The normal CBC does not rule out iron deficiency, as RLS can occur with low iron stores even when hemoglobin is normal 1.

Essential Laboratory Evaluation

Iron studies are the critical first step:

• Serum ferritin
• Transferrin saturation

The 2025 AASM guideline specifically recommends iron supplementation when ferritin is <75 mcg/L or transferrin saturation is <20% 1. These thresholds are much higher than those used for anemia diagnosis—a common pitfall that leads to missed treatment opportunities.

Important Differential Considerations

Diabetic Peripheral Neuropathy vs. RLS

While this patient has diabetes, several features strongly favor RLS over diabetic peripheral neuropathy (DPN) 2, 3:

RLS characteristics present:

• Rest-induced symptoms (DPN symptoms are constant)
• Movement provides relief (DPN does not improve with movement)
• Circadian pattern with evening/night worsening (DPN has no time pattern)
• Urge to move (not typical of DPN)

If uncertainty exists: Nerve conduction studies can help differentiate, but the clinical history is usually sufficient 3.

Metformin Considerations

The patient is on metformin, which has two relevant implications:

• Metformin can cause vitamin B12 deficiency, which may worsen RLS symptoms 4
• Check vitamin B12 level as part of the evaluation
• However, metformin itself does not cause RLS and may actually have modest sleep benefits in some patients 5

Complete Evaluation Panel

Order these labs:

1. Serum ferritin (target >75 mcg/L for RLS treatment)
2. Transferrin saturation (target >20%)
3. Vitamin B12 (metformin-related deficiency screening)
4. Serum creatinine/eGFR (assess kidney function, as ESRD is associated with secondary RLS and affects treatment choices) 1

Clinical Pitfalls to Avoid

• Don't rely on CBC alone—normal hemoglobin does not exclude iron deficiency as a cause of RLS 1
• Don't assume it's diabetic neuropathy—the circadian pattern and rest-induced nature are pathognomonic for RLS 2, 3
• Don't start dopaminergic therapy before checking iron—correcting iron deficiency may resolve symptoms and avoid medication risks 1
• Don't forget B12—metformin users need periodic B12 monitoring, and deficiency can contribute to neurologic symptoms 4

Risk Stratification Context

This patient's comorbidities (diabetes, hypertension, atrial fibrillation) increase her cardiovascular risk, and RLS with sleep disturbance can worsen cardiovascular outcomes 6. Addressing RLS is not merely symptomatic—improving sleep quality may have broader health benefits in this high-risk population.