From the Guidelines
Hyponatremia is most commonly caused by excessive water intake relative to sodium levels, with the most frequent causes including medications, syndrome of inappropriate antidiuretic hormone secretion (SIADH), heart failure, liver cirrhosis, and kidney disease. The most frequent causes of hyponatremia include:
- Medications (particularly thiazide diuretics, SSRIs, and certain antipsychotics)
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Heart failure
- Liver cirrhosis
- Kidney disease Other important causes include:
- Adrenal insufficiency
- Hypothyroidism
- Excessive sweating
- Vomiting or diarrhea
- Drinking too much water during endurance exercise Certain conditions like polydipsia (excessive water drinking) can dilute sodium levels, while others like heart failure or cirrhosis cause sodium and water retention with proportionally more water retained, as noted in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1. The body normally maintains sodium balance through complex mechanisms involving the kidneys, adrenal glands, and brain, but when these regulatory systems are disrupted by disease or medications, hyponatremia can develop. Symptoms typically appear when sodium levels fall rapidly or drop below 130 mEq/L and may include headache, confusion, seizures, and in severe cases, coma. Treatment depends on identifying and addressing the underlying cause while carefully correcting sodium levels at an appropriate rate to avoid complications, as recommended in the 2013 ACCF/AHA guideline for the management of heart failure 1.
From the FDA Drug Label
In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal.
The most common causes of hyponatremia include:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH) These conditions were identified as underlying causes of euvolemic or hypervolemic hyponatremia in patients treated with tolvaptan 2.
From the Research
Causes of Hyponatremia
The most common causes of hyponatremia can be categorized based on the volume status of the patient. These include:
- Hypovolemic hyponatremia, which may be caused by severe burns, gastrointestinal losses, and acute water overload 3
- Euvolemic hyponatremia, which can be caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion, medications, and reset osmostat syndrome 3, 4, 5
- Hypervolemic hyponatremia, which may be caused by congestive heart failure, liver cirrhosis, and renal disease 3, 6, 7
Specific Causes
Some specific causes of hyponatremia include:
- Medications, which can cause euvolemic hyponatremia 3, 5
- SIADH, which is a common cause of euvolemic hyponatremia 3, 4, 5
- Liver cirrhosis, which can cause hypervolemic hyponatremia 6, 7
- Congestive heart failure, which can cause hypervolemic hyponatremia 3, 4
- Renal disease, which can cause hypervolemic hyponatremia 3, 4
Diagnosis and Classification
Diagnosing the underlying cause of hyponatremia is crucial for effective treatment. This can be done by categorizing patients according to their fluid volume status (hypovolemic, euvolemic, or hypervolemic) and measuring plasma osmolality and urinary sodium concentration 3, 4.