What causes hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia is caused by several mechanisms that disrupt the body's sodium-water balance, including excessive water intake, medications, and medical conditions such as heart failure, cirrhosis, kidney disease, and SIADH. The most recent and highest quality study, 1, provides guidance on the management of hyponatremia in patients with cirrhosis, which can be applied to the general management of hyponatremia. Some common causes of hyponatremia include:

• Excessive water intake (polydipsia)
• Medications like thiazide diuretics, SSRIs, carbamazepine, and certain antipsychotics
• Medical conditions such as heart failure, cirrhosis, kidney disease, and SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion)
• Severe vomiting or diarrhea, which can deplete sodium
• Adrenal insufficiency, which reduces aldosterone production needed for sodium retention
• Excessive sweating during intense exercise without proper electrolyte replacement
• Certain endocrine disorders like hypothyroidism and drinking too much water during endurance events ("exercise-associated hyponatremia") Symptoms of hyponatremia can range from mild (headache, confusion, nausea) to severe (seizures, coma), and treatment depends on the severity and underlying cause, from fluid restriction for mild cases to hypertonic saline for severe, symptomatic cases. Addressing the underlying cause is essential for long-term management, as stated in 1. In patients with cirrhosis, the management of hyponatremia depends on the etiology, chronicity, severity, and urgency, and may involve fluid restriction, discontinuation of diuretics, and administration of hypertonic sodium chloride or vasopressin receptor antagonists, as recommended in 1 and 1. It is also important to note that the correction of chronic hyponatremia should be done gradually, with a goal rate of increase of serum sodium of 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, to avoid the risk of central pontine myelinolysis, as stated in 1 and 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 (low sodium levels) include:

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

From the Research

Causes of Hyponatremia

Hyponatremia, or low sodium levels, can be caused by various factors, including:

• Water retention, which is the most common cause 3
• Certain medications 4
• Excessive alcohol consumption 4
• Very low-salt diets 4
• Excessive free water intake during exercise 4
• Cirrhosis and portal hypertension, which can lead to excessive renal retention of water relative to sodium 5
• Heart failure, which can cause hyponatremia due to increased release of arginine vasopressin 6
• Nephrotic syndrome 7
• Infusion of 5% glucose solutions 7
• Drugs that stimulate ADH secretion 7
• Inflammation and IL-6, which can stimulate non-osmotic ADH release 7

Classification of Hyponatremia

Hyponatremia can be classified into three categories based on fluid volume status:

• Hypovolemic hyponatremia, which is treated with normal saline infusions 4
• Euvolemic hyponatremia, which is treated with restricting free water consumption or using salt tablets or intravenous vaptans 4
• Hypervolemic hyponatremia, which is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction 4

Symptoms and Treatment

Symptoms of hyponatremia can range from mild to severe and include:

• Nausea, vomiting, weakness, headache, and mild neurocognitive deficits 4
• Delirium, confusion, impaired consciousness, ataxia, seizures, and brain herniation 4 Treatment of hyponatremia depends on the underlying cause and severity of symptoms, and may include:
• Treating the underlying cause 3
• Restricting free water consumption 4
• Using salt tablets or intravenous vaptans 4
• Administering hypertonic saline in severe cases 3, 4
• Using vasopressin receptor antagonists, such as tolvaptan, to increase free water excretion and raise serum sodium concentration 5, 6