What are the causes of chronic hyponatremia?

Causes of Chronic Hyponatremia

Chronic hyponatremia (serum sodium <135 mEq/L persisting >48 hours) results from sustained arginine vasopressin (AVP) excess impairing free-water excretion, with causes categorized by volume status: hypovolemic (renal or extrarenal sodium losses), euvolemic (SIADH, hypothyroidism, adrenal insufficiency), and hypervolemic (heart failure, cirrhosis, advanced renal failure). 1

Hypovolemic Causes

Renal sodium losses:

• Diuretic use (thiazides and loop diuretics) 1, 2
• Cerebral salt wasting (CSW) in neurosurgical patients 1, 3
• Salt-losing nephropathy 3
• Adrenal insufficiency 3, 2
• Mineralocorticoid deficiency 1

Extrarenal sodium losses:

• Gastrointestinal losses (vomiting, diarrhea) 3, 2
• Burns 1
• Third-space fluid sequestration 2

Clinical clue: Urine sodium <30 mmol/L suggests extrarenal losses, while >20 mmol/L indicates renal losses. 1, 3

Euvolemic Causes (Most Common)

Syndrome of Inappropriate Antidiuresis (SIADH):

• Malignancies (especially small cell lung cancer, affecting 1-5% of lung cancer patients) 1, 3
• CNS disorders (meningitis, encephalitis, subarachnoid hemorrhage, traumatic brain injury) 4, 1
• Pulmonary diseases (pneumonia, tuberculosis) 4, 1
• Medications (antidepressants including trazodone, SSRIs, carbamazepine, oxcarbazepine, NSAIDs, opiates) 1, 2
• Postoperative states 4, 1
• Pain, nausea, and stress (nonosmotic AVP stimuli) 4, 1

Diagnostic criteria: Hypotonic hyponatremia with inappropriately elevated urine osmolality (>500 mOsm/kg), urine sodium >20-40 mEq/L, euvolemia on exam, and normal thyroid/adrenal function. 3 Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH. 1, 3

Endocrine disorders:

• Hypothyroidism 1, 3
• Adrenal insufficiency 1, 3

Other causes:

• Excessive free water intake during exercise 2
• Beer potomania (very low-salt diet with excessive beer consumption) 1
• Polydipsia 3

Hypervolemic Causes

Edematous states with impaired free water excretion:

• Advanced cirrhosis with portal hypertension (affects ~60% of cirrhotic patients with ascites) 1, 2
• Congestive heart failure 1, 2
• Advanced renal failure 1, 3
• Nephrotic syndrome 2

Pathophysiology: Systemic vasodilation and decreased effective plasma volume trigger non-osmotic AVP hypersecretion and enhanced proximal tubular sodium reabsorption, leading to dilutional hyponatremia despite total body sodium excess. 1

Critical Distinguishing Features

Volume status assessment is essential but challenging:

• Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) 1, 3
• Hypovolemia: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 1, 3
• Hypervolemia: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1, 3
• Euvolemia: absence of both hypovolemic and hypervolemic signs 1

Laboratory differentiation:

• Urine sodium <30 mmol/L: extrarenal losses (71-100% PPV for saline responsiveness) 1, 3
• Urine sodium >20-40 mmol/L with high urine osmolality (>300-500 mOsm/kg): SIADH or renal losses 1, 3
• Serum uric acid <4 mg/dL: strongly suggests SIADH (73-100% PPV) 1, 3

Common Pitfalls

In neurosurgical patients, distinguishing SIADH from cerebral salt wasting is critical—both present with elevated urine sodium but require opposite treatments (fluid restriction vs. volume replacement). 1, 3 CSW shows true hypovolemia with CVP <6 cm H₂O, while SIADH demonstrates euvolemia with normal CVP. 3

Even mild chronic hyponatremia (130-135 mEq/L) increases mortality 60-fold (11.2% vs 0.19%), fall risk (21% vs 5%), and causes neurocognitive deficits—it should never be dismissed as clinically insignificant. 1, 5

Hospital-acquired hyponatremia from hypotonic IV fluids in the setting of elevated AVP (from pain, nausea, postoperative state, pneumonia) is the most common cause in hospitalized children and adults, affecting 15-30%. 4 This is entirely preventable by using isotonic maintenance fluids. 4, 1