What causes hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia is primarily caused by an imbalance of sodium in the body, resulting from excessive water intake, certain medications, or underlying medical conditions such as heart failure, liver cirrhosis, kidney disease, and SIADH, which disrupt the body's electrolyte balance. The most common causes of hyponatremia include:

• Excessive water intake
• Medications like thiazide diuretics, SSRIs, and certain antipsychotics
• Medical conditions such as heart failure, liver cirrhosis, kidney disease, and SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion)
• Endocrine disorders like adrenal insufficiency and hypothyroidism
• Severe vomiting or diarrhea, which can cause sodium loss
• Certain lifestyle factors, including excessive water consumption during endurance sports without adequate sodium replacement, as noted in 1. According to 1, when the serum sodium concentration decreases to less than 130 mmol/L in patients with liver cirrhosis and ascites, most are dilutional hyponatremia, which requires special attention due to its association with poor prognosis and multiple complications. The underlying mechanism typically involves either sodium loss, water retention, or a combination of both, disrupting the body's careful electrolyte balance, which affects cellular function throughout the body, particularly in the brain, explaining why symptoms often include headache, confusion, seizures, and in severe cases, coma, as discussed in 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)

The causes of hyponatremia include:

• Heart failure
• Liver cirrhosis
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Other causes 2 2

From the Research

Causes of Hyponatremia

• Hyponatremia can be caused by various factors, including defective water excretion, usually due to elevated serum vasopressin levels, or excessive fluid intake 3
• Thiazide-induced hyponatremia is a common cause of decreased sodium levels in elderly individuals, especially in those with certain risk factors such as heart failure, liver disease, or malignancy 4, 5
• The use of selective serotonin reuptake inhibitors (SSRIs) can also contribute to the development of hyponatremia, particularly when combined with thiazide diuretics 6
• Hyponatremia is frequently encountered in patients with heart failure, and its association with adverse outcomes is well-established in this population 7

Mechanisms of Hyponatremia

• Thiazide diuretics can impair diluting ability, stimulate vasopressin release, reduce glomerular filtration, and enhance proximal water reabsorption, leading to water retention and severe hyponatremia 5
• SSRIs can cause hyponatremia through the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 6
• Heart failure can lead to hyponatremia due to various mechanisms, including increased vasopressin levels and decreased renal function 7

Risk Factors for Hyponatremia

• Elderly individuals, especially those with certain comorbidities such as heart failure, liver disease, or malignancy, are at increased risk of developing thiazide-associated hyponatremia 4
• Patients taking multiple medications, such as non-steroidal anti-inflammatory drugs, SSRIs, or tricyclic antidepressants, are also at increased risk 4
• Frail elderly patients with chronically high water intake or those who depend on the excretion of maximally dilute urine to maintain fluid balance are at risk of developing thiazide-induced hyponatremia 5