What are the causes of hyponatremia?

Causes of Hyponatremia

Hyponatremia (serum sodium <135 mmol/L) has multiple etiologies that can be classified based on the patient's volume status as hypovolemic, euvolemic, or hypervolemic. 1, 2

Classification Based on Volume Status

1. Hypovolemic Hyponatremia

• Renal losses:

  • Diuretic therapy (especially thiazides) 1, 3
  • Salt-losing nephropathies 1
  • Cerebral salt wasting 1
  • Adrenal insufficiency 4

• Extra-renal losses:

  • Gastrointestinal losses (vomiting, diarrhea) 1, 2
  • Excessive sweating 1
  • Third-space losses (burns, pancreatitis) 1
  • Inadequate sodium intake 1

2. Euvolemic Hyponatremia

• Syndrome of Inappropriate ADH secretion (SIADH) 1, 2
• Medications (carbamazepine, cyclophosphamide, vincristine) 4, 1
• Hypothyroidism 1
• Glucocorticoid deficiency 1
• Primary polydipsia 1, 5
• Reset osmostat syndrome 1
• Low solute intake ("beer potomania") 1

3. Hypervolemic Hyponatremia

• Congestive heart failure 1, 2
• Liver cirrhosis 1, 2
• Nephrotic syndrome 1
• Renal failure 4, 1

Classification Based on Serum Osmolality

1. Hypotonic Hyponatremia (Low Osmolality)

• Most common form of true hyponatremia 1, 5
• Includes all causes listed under volume status classification 1

2. Isotonic Hyponatremia (Normal Osmolality)

• Pseudohyponatremia due to hyperlipidemia 1, 2
• Pseudohyponatremia due to hyperproteinemia 1
• Post-transurethral prostatic resection syndrome 2

3. Hypertonic Hyponatremia (High Osmolality)

• Hyperglycemia 1, 2
• Mannitol administration 1
• Other osmotically active substances 1

High-Risk Populations

• Pediatric patients receiving hypotonic maintenance IV fluids 4
• Patients with congenital or acquired heart disease 4
• Patients with liver disease 4, 1
• Patients with renal failure or dysfunction 4
• Patients receiving certain medications:
  • Desmopressin administered perioperatively for Von Willebrand disease 4
  • Antiepileptic medications (carbamazepine) 4
  • Chemotherapeutic agents (IV cyclophosphamide, vincristine) 4
• Elderly patients, especially those on thiazide diuretics 1, 3
• Postoperative patients 1
• Endurance athletes 6

Common Pitfalls in Diagnosis

• Failing to assess volume status accurately 1
• Misdiagnosing cerebral salt wasting as SIADH in neurosurgical patients 1
• Overlooking mild hyponatremia (130-134 mmol/L) which can still cause symptoms 1, 7
• Not recognizing pseudohyponatremia in cases of hyperlipidemia or hyperproteinemia 1, 2
• Ignoring medication history, especially diuretics, which are one of the most common causes of severe hyponatremia 3
• Not measuring urine sodium and osmolality to help distinguish between different causes 1
• Failing to recognize that patients receiving isotonic maintenance IV fluids can still develop hyponatremia if they receive IV medications containing free water or consume additional free water enterally 4

Laboratory Evaluation

• Serum osmolality to distinguish between hypotonic, isotonic, and hypertonic hyponatremia 1, 2
• Urine sodium concentration: <30 mmol/L suggests hypovolemic hyponatremia; >20 mmol/L with high urine osmolality suggests SIADH 1
• Urine osmolality to assess renal water handling 1
• Thyroid function tests to rule out hypothyroidism 1
• Cortisol level to rule out adrenal insufficiency 1
• Liver function tests to assess for cirrhosis 1
• Serum glucose to rule out hyperglycemia-induced hyponatremia 1, 2

Understanding the underlying cause of hyponatremia is crucial for appropriate management and prevention of complications such as osmotic demyelination syndrome from overly rapid correction 1, 5.