Causes of Hyponatremia
Classification by Volume Status
Hyponatremia should be systematically classified based on the patient's volume status—hypovolemic, euvolemic, or hypervolemic—as this directly determines both the underlying cause and appropriate treatment approach. 1
Hypovolemic Hyponatremia
Renal losses:
- Diuretic therapy (particularly thiazides and loop diuretics) 1, 2
- Salt-losing nephropathies 1
- Cerebral salt wasting (especially in neurosurgical patients) 1
- Adrenal insufficiency 1
Extrarenal losses:
Euvolemic Hyponatremia
Syndrome of Inappropriate ADH Secretion (SIADH):
- Malignancy (particularly small cell lung cancer) 1, 2
- CNS disorders (meningitis, encephalitis, stroke, subarachnoid hemorrhage) 1
- Pulmonary disease (pneumonia, tuberculosis) 1
Medications:
- Carbamazepine 1
- Cyclophosphamide 1
- Vincristine 1
- Antiepileptic medications 1
- Desmopressin 1
- SSRIs and other antidepressants 2
Endocrine disorders:
Other causes:
- Primary polydipsia 1
- Reset osmostat syndrome 1, 2
- Low solute intake (beer potomania, tea-and-toast diet) 1
Hypervolemic Hyponatremia
- Congestive heart failure 1, 2
- Liver cirrhosis with ascites 1, 2
- Nephrotic syndrome 1
- Renal failure 1, 2
Pathophysiologic Mechanisms
All forms of hypotonic hyponatremia develop through only two general mechanisms: 4
Defective water excretion (most common)—usually due to elevated serum vasopressin levels causing impaired free water clearance 3, 4
Excessive fluid intake—overwhelming normal renal water excretion capacity, seen in primary polydipsia or acute water intoxication 4
High-Risk Populations
Specific patient groups require heightened surveillance: 1
- Pediatric patients receiving hypotonic maintenance IV fluids 1
- Patients with liver disease, renal failure, or dysfunction 1
- Patients receiving desmopressin, antiepileptic medications, or chemotherapeutic agents 1
- Elderly patients on multiple medications 2
- Endurance athletes (exercise-associated hyponatremia) 5
Diagnostic Approach
Initial laboratory evaluation should include: 1
- Serum osmolality—distinguishes hypotonic (most common), isotonic (pseudohyponatremia), and hypertonic hyponatremia (hyperglycemia) 1, 2
- Urine sodium concentration—helps differentiate renal from extrarenal losses (cutoff typically 30 mmol/L) 1, 2
- Urine osmolality—assesses renal water handling capacity 1
- Thyroid function tests and cortisol level—rules out endocrine causes 1
- Liver function tests and serum glucose—identifies underlying systemic conditions 1
Key diagnostic distinctions: 2
- High urinary sodium (>30 mmol/L) with low plasma osmolality suggests renal disorders, endocrine deficiencies, SIADH, or medication effects 2
- Low urinary sodium (<30 mmol/L) indicates extrarenal losses (GI losses, burns) or acute water overload 2
- Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH (though may include cerebral salt wasting) 1
Clinical Significance
Hyponatremia represents the most common electrolyte disorder in clinical medicine and hospitalized patients. 3 Even mild hyponatremia (130-135 mmol/L) is associated with increased mortality (60-fold increase when <130 mmol/L), falls (21% vs 5% in normonatremic patients), attention deficits, gait instability, osteoporosis, and fractures. 1, 6
Common Diagnostic Pitfalls
Critical errors to avoid: 1
- Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant—even this range increases fall risk and mortality 1
- Failing to assess volume status accurately, which is essential for determining the underlying cause 2
- Not distinguishing between SIADH and cerebral salt wasting in neurosurgical patients—these require fundamentally different treatments 1
- Overlooking medication-induced hyponatremia, particularly with diuretics, SSRIs, and chemotherapy agents 1, 2