Causes of Chronic Hyponatremia
Chronic hyponatremia is primarily caused by disorders affecting sodium and water homeostasis, with the most common causes being medications, syndrome of inappropriate antidiuretic hormone (SIADH), and conditions causing volume overload such as heart failure, cirrhosis, and renal disease. 1, 2
Classification Based on Volume Status
Hyponatremia is best categorized according to the patient's volume status:
Hypovolemic Hyponatremia
- Excessive diuretic use, particularly in patients with liver cirrhosis 3
- Gastrointestinal losses (vomiting, diarrhea) 1
- Severe burns with fluid losses 3
- Renal salt wasting 4
- Adrenal insufficiency 3
Euvolemic Hyponatremia
- Syndrome of Inappropriate ADH secretion (SIADH) 3, 2
- Medications (psychotropic drugs, anticonvulsants, antidepressants) 5
- Hypothyroidism 3
- Reset osmostat syndrome 3
- Primary polydipsia (excessive water intake) 4
Hypervolemic Hyponatremia
- Congestive heart failure 3, 1
- Liver cirrhosis with portal hypertension 3, 1
- Advanced kidney disease 1
- Nephrotic syndrome 6
Medication-Induced Hyponatremia
Medications are among the most common causes of chronic hyponatremia:
- Diuretics (especially thiazides) 5
- Antidepressants (SSRIs, TCAs) 5
- Antipsychotics 5
- Anticonvulsants (carbamazepine, oxcarbazepine) 3
- Chemotherapeutic agents (cyclophosphamide, vincristine) 6
- Proton pump inhibitors 5
- Desmopressin 6
- Angiotensin-converting enzyme inhibitors 5
- Hypoglycemic agents 5
- Amiodarone 5
Endocrine Causes
- Hypothyroidism (reduced free water clearance) 3
- Adrenal insufficiency (cortisol deficiency) 3
- SIADH (tumors, CNS disorders, pulmonary diseases) 3, 2
Other Important Causes
- Chronic alcohol consumption (beer potomania) 3, 4
- Very low-salt diets 4
- Advanced age (altered water homeostasis) 2
- Post-operative state 7
- Cerebral salt wasting in neurosurgical patients 3
Clinical Significance
- Even mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 2
- Patients with hyponatremia have a higher rate of falls (23.8% vs 16.4%) and new fractures (23.3% vs 17.3%) compared to those with normal sodium levels 2
- In cirrhotic patients, sodium <130 mmol/L increases risk for hepatic encephalopathy (OR 2.36), spontaneous bacterial peritonitis (OR 3.40), and hepatorenal syndrome (OR 3.45) 3
Diagnostic Approach
When evaluating chronic hyponatremia:
- Measure serum and urine osmolality and urine electrolytes 3
- Assess extracellular fluid volume status 3
- Check thyroid and adrenal function 3
- Review all medications 5
- Consider measuring uric acid (levels <4 mg/dL have a positive predictive value of 73-100% for SIADH) 3
Common Pitfalls
- Ignoring mild hyponatremia (130-134 mEq/L) as clinically insignificant 3
- Failing to recognize medication-induced hyponatremia 5
- Misdiagnosing volume status, especially in heart failure patients 3
- Not distinguishing between SIADH and cerebral salt wasting in neurosurgical patients 3
- Overlooking chronic hyponatremia as a secondary cause of osteoporosis 2
Understanding the underlying cause of chronic hyponatremia is crucial for appropriate management and preventing complications associated with this common electrolyte disorder.