What are the causes of hyponatremia in adults?

Causes of Hyponatremia in Adults

Classification by Volume Status

Hyponatremia should be classified based on extracellular fluid volume status—hypovolemic, euvolemic, or hypervolemic—as this directly determines the underlying cause and guides treatment. 1

Hypovolemic Hyponatremia (Decreased Total Body Sodium and Water)

Renal Losses:

• Excessive diuretic use, particularly thiazides and loop diuretics in patients with liver cirrhosis 2
• Adrenal insufficiency (mineralocorticoid deficiency) 2
• Cerebral salt wasting syndrome in neurosurgical patients, especially with subarachnoid hemorrhage 1
• Salt-wasting nephropathies 3

Extrarenal Losses:

• Severe burns with fluid losses 2
• Gastrointestinal losses (vomiting, diarrhea) 3
• Third-space fluid sequestration 3

Diagnostic clue: Urine sodium <30 mmol/L suggests extrarenal losses, while >20 mmol/L indicates renal sodium wasting 1

Euvolemic Hyponatremia (Normal Total Body Sodium, Increased Water)

Syndrome of Inappropriate Antidiuretic Hormone (SIADH):

• Malignancies (especially small cell lung cancer, affecting 1-5% of lung cancer patients) 1, 4
• CNS disorders (meningitis, encephalitis, stroke, subarachnoid hemorrhage) 2, 4
• Pulmonary diseases (pneumonia, tuberculosis) 2, 4
• Postoperative states and acute pain/nausea/stress 1, 5

Medications:

• Antidepressants (SSRIs, trazodone—particularly high risk) 1, 2
• Anticonvulsants (carbamazepine, oxcarbazepine) 2
• Chemotherapeutic agents (cyclophosphamide, vincristine) 2
• Desmopressin 2

Endocrine Disorders:

• Hypothyroidism 2, 3
• Glucocorticoid deficiency 3

Other:

• Reset osmostat syndrome 2
• Excessive water intake during endurance exercise (exercise-associated hyponatremia, affecting 3-22% of marathon runners) 6
• Beer potomania (excessive alcohol consumption with poor solute intake) 1

Diagnostic clue: Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg suggests SIADH; serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2

Hypervolemic Hyponatremia (Increased Total Body Sodium and Water)

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

Pathophysiology: Non-osmotic hypersecretion of vasopressin due to perceived arterial underfilling, enhanced proximal nephron sodium reabsorption, and impaired free water clearance 1

Key Diagnostic Pitfalls

Critical distinction in neurosurgical patients: Cerebral salt wasting (CSW) presents similarly to SIADH but requires opposite treatment—volume and sodium replacement rather than fluid restriction. CSW is characterized by true hypovolemia with CVP <6 cm H₂O, high urine sodium despite volume depletion, and is more common than SIADH in patients with subarachnoid hemorrhage. 1

Hospital-acquired hyponatremia from hypotonic IV fluids in the setting of elevated ADH affects 15-30% of hospitalized patients and is entirely preventable by using isotonic maintenance fluids. 1

Clinical Significance

Even mild hyponatremia (130-135 mmol/L) is associated with increased mortality, falls (21% vs 5% in normonatremic patients), fractures, and cognitive impairment. 1, 7 Sodium levels <130 mmol/L in cirrhotic patients increase risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36). 1, 2