What are the causes of hyponatremia beyond diuretic use?

From the Guidelines

Hyponatremia has numerous causes beyond diuretic use, including syndrome of inappropriate antidiuretic hormone secretion (SIADH), excessive water intake, endocrine disorders, heart failure, cirrhosis, and nephrotic syndrome, among others. The causes of hyponatremia can be broadly categorized into hypovolemic, euvolemic, and hypervolemic types. Hypovolemic hyponatremia can result from gastrointestinal losses, renal disorders, or certain medications 1. Euvolemic hyponatremia is often associated with SIADH, which can be caused by various factors, including certain cancers, pulmonary diseases, CNS disorders, or medications like SSRIs, carbamazepine, and certain antipsychotics. Hypervolemic hyponatremia is commonly seen in patients with heart failure, cirrhosis, and nephrotic syndrome, where increased ADH secretion and fluid retention contribute to the development of hyponatremia 1.

Key Causes of Hyponatremia

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Excessive water intake (psychogenic polydipsia)
• Endocrine disorders (adrenal insufficiency, hypothyroidism, diabetes insipidus)
• Heart failure
• Cirrhosis
• Nephrotic syndrome
• Gastrointestinal losses (vomiting, diarrhea)
• Renal disorders (salt-wasting nephropathies, renal tubular acidosis)
• Certain medications (oxcarbazepine, NSAIDs, some antibiotics)
• Nutritional deficiencies (malnourished or alcoholic patients)
• Exercise-associated hyponatremia Identifying the specific cause of hyponatremia is crucial for appropriate management, as treatment approaches differ significantly depending on the underlying etiology 1. The management of hyponatremia should prioritize the correction of the underlying cause, and treatment strategies may include fluid restriction, hypertonic saline administration, and the use of vasopressin receptor antagonists in certain cases.

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 causes of hyponatremia beyond diuretic use include:

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

From the Research

Causes of Hyponatremia

• Hyponatremia can be caused by various factors beyond diuretic use, including:
  • Excessive renal retention of water relative to sodium due to reduced solute-free water clearance 3
  • Increased release of arginine vasopressin 3, 4
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH) 5
  • Cardiac failure 5, 3, 4
  • Liver cirrhosis 5, 3, 4
  • Nephrotic syndrome 4, 6
  • Excessive free water intake during exercise 7
  • Very low-salt diets 7
  • Excessive alcohol consumption 7
  • Inflammation and IL-6 induced non-osmotic ADH release 6
  • Infusion of 5% glucose solutions 6
  • Drugs that stimulate ADH secretion 6
  • Diarrhea, vomiting, or other gastrointestinal fluid losses 5
  • Burns 6
  • Mineralocorticoid deficiency 6
  • Nephritis 6

Classification of Hyponatremia

• Hyponatremia can be classified into three types:
  • Euvolemic hyponatremia (e.g., SIADH) 5
  • Hypervolemic hyponatremia (e.g., cardiac failure, liver cirrhosis) 5, 3, 4
  • Hypovolemic hyponatremia (e.g., diarrhea, vomiting, or other gastrointestinal fluid losses) 5