Is restless leg syndrome (RLS) related to low calcium levels (hypocalcemia)?

Relationship Between Restless Leg Syndrome and Hypocalcemia

While restless leg syndrome (RLS) is primarily associated with iron deficiency and dopamine dysfunction, there is limited evidence directly linking RLS to hypocalcemia, though calcium metabolism disorders like hyperparathyroidism have been reported as uncommon secondary causes of RLS.

Pathophysiology of RLS

• RLS is a sleep-related movement disorder characterized by an urge to move the legs when immobile, often associated with uncomfortable sensations that are relieved by movement and worsen in the evening or at night 1.
• The primary pathophysiological mechanism of RLS involves brain iron deficiency, particularly in specific brain regions, which affects dopamine transport in the substantia nigra 1.
• Iron deficiency appears to play a critical role in most patients with this disorder, even when serum iron studies are normal 1.

Known Secondary Causes of RLS

• Common secondary causes of RLS include:
  • Iron deficiency (the most well-established cause) 2
  • End-stage renal disease (ESRD) 1
  • Pregnancy 1
  • Peripheral neuropathy 1
• Medications that can exacerbate RLS include tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists (antipsychotics) 1.
• Social or lifestyle factors that contribute to RLS symptoms include increased BMI, caffeine intake, sedentary lifestyle, tobacco use, and lower income 1.

Calcium and RLS Connection

• While not commonly listed as a primary cause, there is a case report of RLS associated with primary hyperparathyroidism (which causes hypercalcemia), where the patient experienced complete resolution of RLS symptoms after parathyroidectomy and normalization of calcium levels 3.
• This suggests that disorders of calcium metabolism may potentially influence RLS symptoms in some cases, though the evidence is limited 3.
• The American Academy of Sleep Medicine guidelines do not specifically mention calcium levels in their assessment or treatment recommendations for RLS 1, 2.

Diagnostic Approach for RLS

• The diagnosis of RLS is primarily clinical, based on the following criteria:
  • An urge to move the legs, often accompanied by uncomfortable sensations
  • Symptoms begin or worsen during periods of rest or inactivity
  • Symptoms are partially or totally relieved by movement
  • Symptoms worsen in the evening or at night 1
• Laboratory testing should include:
  • Serum ferritin (primary recommendation) 2
  • Transferrin saturation 2
  • Consider calcium, parathyroid hormone, and vitamin D levels if suspecting a calcium metabolism disorder 3

Management Implications

• If RLS is suspected and hypocalcemia is present:
  • First, correct the calcium deficiency and monitor for symptom improvement 3.
  • Evaluate for underlying causes of hypocalcemia, such as vitamin D deficiency or hypoparathyroidism.
• For persistent RLS symptoms after addressing calcium issues, follow standard RLS treatment guidelines:
  • Check iron status and supplement if ferritin ≤75 ng/mL or transferrin saturation <20% 2.
  • First-line pharmacological treatment includes alpha-2-delta ligands (gabapentin, pregabalin) 1.
  • Address potential exacerbating factors like caffeine, alcohol, and certain medications 2.

Clinical Pearls

• Always assess both iron and calcium metabolism in patients with RLS, as correcting underlying metabolic abnormalities may resolve symptoms without requiring long-term medication 3, 2.
• Consider calcium disorders in treatment-resistant RLS cases or when RLS occurs with other symptoms suggestive of calcium metabolism disorders 3.
• Be cautious with dopaminergic agents as they can lead to augmentation (worsening of symptoms) with long-term use 1, 4.