What lab tests should be ordered for a 65-year-old female with worsening insomnia and an urge to move her legs at rest and night, who has hypertension, diabetes mellitus type 2, and atrial fibrillation, and is taking metformin, lisinopril, atorvastatin, and apixaban?

Laboratory Testing for Restless Legs Syndrome in a 65-Year-Old Female

Serum ferritin level should be the first laboratory test ordered for this patient with symptoms of restless legs syndrome (RLS), as iron deficiency is a major treatable cause of RLS. 1

Diagnostic Assessment

The patient's symptoms strongly suggest RLS, characterized by:

• Urge to move legs at rest and night
• Worsening insomnia
• Symptoms occurring during periods of inactivity

Primary Laboratory Testing

1. Serum ferritin level

   • Most important initial test for RLS
   • Values <50 ng/mL are consistent with iron-deficient RLS 1
   • Iron supplementation is recommended for ferritin levels <75 ng/mL 1

2. Complete iron studies

   • Serum iron
   • Total iron binding capacity (TIBC)
   • Transferrin saturation (should be ≥20%)

Secondary Laboratory Testing

After obtaining iron studies, the following tests should be considered to evaluate for secondary causes of RLS:

• Complete blood count (CBC)

  • Already performed and reported as normal in this patient
  • Important to confirm absence of anemia

• Basic metabolic panel

  • To assess renal function (end-stage renal disease is associated with RLS) 2
  • Particularly important given patient's diabetes and hypertension

• Liver function tests

  • To evaluate hepatic metabolism of medications

• HbA1c

  • To assess diabetes control (diabetes is a potential contributor to RLS)

• Thyroid function tests

  • To rule out thyroid disorders as secondary causes 1

Clinical Implications

Iron Deficiency and RLS

Iron deficiency is particularly relevant in this patient for several reasons:

• Female gender (higher risk of iron deficiency)
• Age 65 (RLS prevalence increases with age) 2
• Taking apixaban (may contribute to occult blood loss)
• Diabetes (may affect iron metabolism)

Medication Considerations

The patient's current medications should be reviewed as potential contributors to RLS:

• Metformin: Generally not associated with RLS
• Lisinopril: Not typically associated with RLS
• Atorvastatin: Some case reports of RLS association
• Apixaban: May contribute to iron deficiency through minor bleeding

Treatment Approach

If iron deficiency is identified:

1. Iron supplementation for ferritin <75 ng/mL or transferrin saturation <20% 1
2. Monitor response to iron therapy before considering other medications

If iron levels are normal, pharmacologic options include:

1. Alpha-2-delta ligands (pregabalin or gabapentin) as first-line therapy 1
2. Dopamine agonists (ropinirole, pramipexole, or rotigotine) as alternative first-line options 1

Clinical Pearls

• RLS affects approximately 10% of the general population, with higher prevalence in women and older adults 2
• Secondary RLS can result from medical conditions with iron deficiency in common, including iron-deficiency anemia, end-stage renal disease, and pregnancy 2
• The impairment of dopamine transport in the substantia nigra due to reduced intracellular iron appears to play a critical role in most patients with RLS 2
• Augmentation (paradoxical worsening of symptoms) is a significant concern with long-term dopamine agonist use 1

Remember that while CBC was normal, this does not rule out iron deficiency without anemia, which is why specific iron studies are essential in the evaluation of RLS.