What causes recurrent hyponatremia?

Recurrent Hyponatremia: Common Causes

Recurrent hyponatremia most commonly results from medications (especially diuretics, antidepressants, and anticonvulsants), chronic SIADH from underlying malignancy or CNS disorders, and hypervolemic states like cirrhosis or heart failure with inadequate fluid restriction. 1, 2

Medication-Induced Causes

Medications are the most frequent culprit in recurrent hyponatremia and must be reviewed at every episode. 2

• Diuretics (thiazides more than loop diuretics) cause hyponatremia through sodium depletion and impaired urinary dilution 3, 2
• Psychotropic drugs including SSRIs, carbamazepine, and other antidepressants induce SIADH 1, 2
• Anticonvulsants particularly carbamazepine and oxcarbazepine are well-established causes 4, 2
• Chemotherapeutic agents including cyclophosphamide and vincristine trigger SIADH 4
• Desmopressin administered perioperatively for Von Willebrand disease places patients at particularly high risk 4

A critical pitfall is failing to recognize that even mild hyponatremia (130-135 mmol/L) from medications increases fall risk 4-fold (21% vs 5%) and mortality 60-fold (11.2% vs 0.19%). 1

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

SIADH is the most common cause of euvolemic recurrent hyponatremia. 3, 5

Underlying Causes of Chronic SIADH:

• Malignancies - particularly small cell lung cancer (affects 1-5% of lung cancer patients) 1
• CNS disorders - stroke, hemorrhage, infection, trauma 1, 3
• Pulmonary diseases - pneumonia, tuberculosis, positive pressure ventilation 1, 3
• Postoperative states with pain, nausea, and stress as nonosmotic AVP stimuli 1

Diagnostic criteria for SIADH include: hypotonic hyponatremia with inappropriately concentrated urine (>100 mOsm/kg), urine sodium >20-40 mmol/L, euvolemic state, and normal thyroid/adrenal/renal function 1, 3

Hypervolemic States

Cirrhosis, heart failure, and nephrotic syndrome cause recurrent hypervolemic hyponatremia through non-osmotic vasopressin release and impaired free water clearance. 4, 6, 7

Cirrhosis-Related Hyponatremia:

• Occurs in ~60% of cirrhotic patients with ascites due to systemic vasodilation and portal hypertension 1
• Sodium <130 mmol/L increases risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
• Only 1.2% of cirrhotic patients with ascites have sodium ≤120 mmol/L, but recurrence is common without addressing underlying liver disease 1

Heart Failure-Related Hyponatremia:

• Results from persistent AVP release due to ineffective renal perfusion from low cardiac output 7
• Recurs when fluid restriction is not maintained or diuretic therapy is inadequate 7

Hospital-Acquired Iatrogenic Causes

Hypotonic IV fluids in hospitalized patients with elevated AVP cause 15-30% of hospital-acquired hyponatremia and are entirely preventable with isotonic maintenance fluids. 4, 1

• Patients with edematous states (CHF, cirrhosis, nephrotic syndrome) receiving typical maintenance rates of isotonic saline risk volume overload 4
• Even patients on isotonic IVFs develop hyponatremia if receiving IV medications containing free water or consuming additional free water enterally 4

High-Risk Clinical Scenarios for Recurrence

Certain patient populations have particularly high recurrence risk requiring closer monitoring: 4, 1

• Patients with congenital or acquired heart disease, liver disease, renal dysfunction, or adrenal insufficiency 4
• Those on multiple medications that impair water excretion (antiepileptics, antidepressants, diuretics) 4, 2
• Neurosurgical patients where distinguishing SIADH from cerebral salt wasting is critical, as CSW recurs without adequate sodium/volume replacement 1

Inadequate Treatment of Underlying Cause

Recurrent hyponatremia often reflects failure to address the root cause: 3, 5

• Inadequate fluid restriction in SIADH (must be <1 L/day) 1, 3
• Continued diuretic use without monitoring in patients with sodium 121-135 mmol/L 1
• Uncontrolled heart failure or cirrhosis with persistent volume overload 6, 7
• Undiagnosed malignancy causing persistent SIADH 1

The single most important principle: identifying and treating the underlying cause is essential to prevent recurrence, not just correcting the sodium level. 1, 3, 5