How does Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) affect electrolyte levels?

From the Guidelines

SIADH primarily affects electrolyte levels by causing hyponatremia, characterized by serum sodium levels below 134 mEq/L, as a result of excessive antidiuretic hormone (ADH) secretion. This condition leads to euvolemic hypoosmolar hyponatremia, where the body retains excess water, diluting the sodium concentration in the blood 1. The key electrolyte disturbances in 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)

These changes are a direct result of the inappropriate secretion of ADH, which activates vasopressin 2 receptors in renal tubules, increasing aquaporins and impairing free water clearance 1. The severity of hyponatremia determines the signs and symptoms, ranging from general weakness, confusion, and headache at serum sodium concentrations of 125 to 130 mEq/L, to life-threatening manifestations when serum sodium levels drop below 120 mEq/L 1.

Management of SIADH focuses on correcting hyponatremia, with treatment options including free water restriction, hypertonic saline, and medications such as demeclocycline, lithium, and vasopressin 2 receptor antagonists 1. Understanding the electrolyte disturbances caused by SIADH is essential for proper diagnosis and management, as severe hyponatremia can lead to seizures, coma, and death if left untreated 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) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal. The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies.

SIADH Effects on Electrolyte Levels:

• SIADH leads to hyponatremia (low serum sodium levels) due to excessive secretion of antidiuretic hormone (ADH), causing the body to retain water and dilute sodium levels.
• The studies show that treatment with tolvaptan increases serum sodium concentrations in patients with hyponatremia, including those with SIADH, indicating that SIADH can cause significant disturbances in electrolyte levels, particularly sodium.
• However, the studies do not provide direct information on the effects of SIADH on other electrolyte levels, such as potassium, chloride, or calcium. 2

From the Research

Effect of SIADH on Electrolyte Levels

• SIADH is a condition characterized by the excessive secretion of antidiuretic hormone (ADH), leading to water retention and resulting in hyponatremia, which is the most frequent electrolyte disorder 3, 4.
• In SIADH, hyponatremia occurs due to a pure disorder of water handling by the kidney, whereas external sodium balance is usually well regulated 4.
• The management of hyponatremia secondary to SIADH is largely dependent on the symptomatology of the patient, and treatment options include fluid restriction, hypertonic saline, and vasopressin receptor antagonists such as vaptans 3, 4.

Treatment Options for SIADH-Associated Hyponatremia

• Vaptans, such as tolvaptan, have been shown to be effective in correcting hyponatremia in patients with SIADH, with a faster correction rate compared to fluid restriction 5.
• Low-dose tolvaptan (3.75-7.5mg) has been found to be effective in increasing serum sodium levels in patients with SIADH-associated hyponatremia, with a lower risk of overcorrection and osmotic demyelination syndrome 6.
• Tolvaptan has also been used successfully in pediatric patients with SIADH, although the dosage should be titrated carefully 7.

Electrolyte Level Changes in SIADH

• Hyponatremia is the primary electrolyte abnormality in SIADH, resulting from water retention and dilution of sodium levels 3, 4.
• The degree and rate of serum sodium reduction can vary, leading to a range of neurological impairments, from subclinical to life-threatening 4.
• Treatment of SIADH aims to correct hyponatremia and prevent further electrolyte imbalances, with careful monitoring of serum sodium levels to avoid overcorrection and osmotic demyelination syndrome 3, 5, 6.