From the Guidelines
Hyponatremia is primarily caused by excessive water intake, inadequate water excretion, or sodium loss, and can be categorized based on volume status into hypovolemic, euvolemic, and hypervolemic hyponatremia. The causes of hyponatremia can be complex and multifactorial, involving various mechanisms such as disruption of ADH regulation or direct interference with the kidney's ability to maintain proper sodium concentration. Some of the key causes include:
- Excessive water intake, which can lead to dilutional hyponatremia
- Inadequate water excretion, often seen in conditions like heart failure, cirrhosis, and kidney disease
- Sodium loss, which can occur through excessive sweating, vomiting, or diarrhea
- Medications, particularly thiazide diuretics, SSRIs, carbamazepine, and NSAIDs, which can disrupt sodium balance
- Endocrine disorders, such as adrenal insufficiency and hypothyroidism, which can also affect sodium balance
- Certain medical conditions, like cystic fibrosis and some cancers, which can cause hyponatremia
- Exercise-associated hyponatremia, which occurs when athletes drink excessive water without adequate sodium replacement, as noted in studies 1, 2. It's essential to identify the underlying cause of hyponatremia to provide appropriate treatment and management, as the treatment approach may vary depending on the cause and volume status of the patient, with the goal of correcting the sodium imbalance while minimizing the risk of complications, as discussed in guidelines 3, 4, 5.
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)
The causes of hyponatremia include:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Other causes 6
From the Research
Causes of Hyponatremia
- Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention 7.
- Common causes of hyponatremia include certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise 8.
- Hyponatremia can be caused by thiazide diuretics, which impair diluting ability and stimulate vasopressin release, leading to water retention and severe hyponatremia 9, 10.
- In patients with cirrhosis and portal hypertension, hyponatremia is caused by excessive renal retention of water relative to sodium due to reduced solute-free water clearance and increased release of arginine vasopressin 11.
- Other causes of hyponatremia include heart failure, liver disease, and malignancy, as well as the use of non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors, and tricyclic antidepressants 10.
Classification of Hyponatremia
- Hyponatremia can be classified into three categories based on fluid volume status: hypovolemic, euvolemic, and hypervolemic 7, 8.
- Hypovolemic hyponatremia is treated with normal saline infusions, while euvolemic hyponatremia is treated with restricting free water consumption or using salt tablets or intravenous vaptans 8.
- Hypervolemic hyponatremia is treated primarily by managing the underlying cause, such as heart failure or cirrhosis, and restricting free water intake 8, 11.
Risk Factors for Hyponatremia
- Certain risk factors increase the likelihood of developing hyponatremia, including large doses of thiazides, comorbidity, and the use of multiple medications 10.
- Elderly individuals are at higher risk of developing thiazide-associated hyponatremia, particularly those with a history of diuretic-associated hyponatremia 10.