Is Syndrome of Inappropriate Antidiuretic Hormone (SIADH) expected with hyponatremia?

From the Guidelines

SIADH is indeed expected to cause low sodium levels in the blood, a condition known as hyponatremia, characterized by serum sodium concentrations below 134 mEq/L, low serum osmolality, and inappropriately high urine osmolality. According to the study by 1, SIADH manifests as euvolemic hypoosmolar hyponatremia, with signs and symptoms determined by the degree of hyponatremia and the acuity of hypoosmolality. The study highlights that hyponatremia in patients with small cell lung cancer is associated with shortened survival, emphasizing the importance of early detection and appropriate management.

Key characteristics of SIADH include:

• Hyponatremia (serum sodium < 134 mEq/L)
• Hypoosmolality (plasma osmolality < 275 mosm/kg)
• Inappropriately high urine osmolality (> 500 mosm/kg)
• Inappropriately high urinary sodium concentration (> 20 mEq/L)
• Absence of hypothyroidism or adrenal insufficiency or volume depletion

The study by 1 also notes that there are no evidence-based guidelines for managing SIADH, and recommended management is based on expert opinion. Free water restriction (< 1 L/d) is a first-line treatment of asymptomatic mild SIADH, and hypertonic 3% saline IV is given in life-threatening or acute symptomatic and severe (< 120 mEq/L) hyponatremia. Additionally, demeclocycline, lithium, and vasopressin 2 receptor antagonists may also be used to correct hyponatremia. It is essential to identify and treat the underlying cause of SIADH, as it can result from various conditions, including certain cancers, brain injuries, medications, or pulmonary diseases.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

SIADH is one of the conditions for which tolvaptan is indicated, and it is associated with low sodium levels. Therefore, SIADH is expected in patients with low sodium. 2

From the Research

SIADH and Low Sodium

• SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion) is a condition characterized by excessive secretion of antidiuretic hormone, leading to water retention and hyponatremia (low sodium levels) 3, 4, 5.
• The diagnosis of SIADH is made based on clinical euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality, and exclusion of pseudohyponatraemia and diuretic use 3.
• Low sodium levels are a key feature of SIADH, with serum sodium concentrations often below 135 mEq/L 4, 6, 7.
• The treatment of SIADH typically involves fluid restriction, with the goal of raising serum sodium levels by 10 mmol/L in 24 hours or 18 mmol/L in 48 hours 3, 5, 6.

Causes and Associations

• SIADH can occur secondary to various conditions, including malignancy, pulmonary disease, central nervous system disorders, and certain medications 3, 4, 5.
• The syndrome is often associated with neurologic diseases, and can cause cerebral edema and brain herniation if left untreated 4, 7.
• Malignancy is a common underlying cause of SIADH, and is often associated with relapse of hyponatremia and requirement for retreatment with Tolvaptan 6.

Treatment and Management

• Fluid restriction is the mainstay of treatment for SIADH, with the goal of raising serum sodium levels and improving symptoms 3, 5, 6.
• Tolvaptan, a vasopressin receptor antagonist, can be used to treat SIADH-associated hyponatremia, particularly in patients with severe symptoms or malignancy 6, 7.
• Optimal management of SIADH-induced hyponatremia can result in improved outcomes and lower health costs, emphasizing the importance of early detection and proper correction 7.