What is the management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

From the Guidelines

The management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should prioritize fluid restriction and pharmacological interventions, with vasopressin receptor antagonists like tolvaptan being a key treatment option for chronic SIADH, as evidenced by the most recent and highest quality study 1.

Pathophysiology of SIADH

SIADH is characterized by the excessive secretion of antidiuretic hormone (ADH), leading to water retention and hyponatremia. The condition is often associated with small cell lung cancer (SCLC) and other lung cancers, as well as other medical conditions. The pathophysiology of SIADH involves the activation of vasopressin 2 receptors in renal tubules, resulting in increased aquaporins and impaired free water clearance.

Management of SIADH

The management of SIADH focuses on treating the underlying cause while addressing hyponatremia through fluid restriction and pharmacological interventions.

• First-line treatment involves restricting fluid intake to less than 1 L/day, which creates a negative water balance by allowing excess water excretion.
• For acute, severe, or symptomatic hyponatremia (serum sodium <120 mEq/L or neurological symptoms), hypertonic saline (3% NaCl) may be administered intravenously at 1-2 mL/kg/hour with careful monitoring to avoid rapid correction.
• Sodium correction should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome.
• Pharmacological options include loop diuretics like furosemide (20-40 mg daily) combined with salt tablets to enhance free water excretion.
• For chronic SIADH, vasopressin receptor antagonists (vaptans) such as tolvaptan (starting at 15 mg daily, maximum 60 mg daily) can be used, though they require careful monitoring for overly rapid sodium correction, as supported by the study 1.
• Urea (30 g daily mixed in beverages) promotes water excretion and is effective for chronic management.
• Demeclocycline (300-600 mg twice daily) induces nephrogenic diabetes insipidus but has fallen out of favor due to nephrotoxicity. Throughout treatment, frequent monitoring of serum sodium, fluid status, and neurological symptoms is essential to guide therapy adjustments and prevent complications, as highlighted in the study 1.

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) The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium.

The management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) includes the use of tolvaptan, a medication that can help increase serum sodium levels. The recommended dosage is 15 mg once daily, which can be increased to 30 mg once daily after at least 24 hours, and up to a maximum of 60 mg once daily as needed. It is essential to monitor serum sodium levels closely and avoid too rapid correction of hyponatremia to prevent serious neurologic sequelae 2.

• Key considerations:
  • Initiate and re-initiate tolvaptan in a hospital setting
  • Monitor serum sodium levels closely
  • Avoid fluid restriction during the first 24 hours of therapy
  • Increase the dose as needed to achieve the desired level of serum sodium
  • Do not administer tolvaptan for more than 30 days to minimize the risk of liver injury

From the Research

SIADH Pathophysiology

• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in hospitalized patients 3.
• Increased concentrations of antidiuretic hormone (ADH) result in retention of free water, increased excretion of sodium, and hyponatremia 3.
• Symptoms generally occur only when hyponatremia is severe (less than or equal to 125 meq/L) and may include anorexia, vomiting, and confusion, followed by seizures, coma, and death 3.

SIADH Management

• Immediate treatment of the symptomatic patient with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance 3.
• If the underlying cause of SIADH cannot be corrected, the treatment of choice for chronic SIADH is fluid restriction 3.
• If fluid restriction is not tolerated by the patient, demeclocycline can be used to induce a negative free-water balance 3.
• Vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH 4.
• Tolvaptan, an oral vasopressin V2-receptor antagonist, induces free water excretion without increasing sodium excretion and may be used to treat hyponatremia in patients with SIADH 5, 6.
• Algorithm-based approaches have been developed for the therapy of SIADH-induced hyponatremia, including acute correction of hyponatremia and treatment of mild or moderate, non-acute hyponatremia 7.

Treatment Considerations

• It is essential to limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent osmotic demyelination 4.
• The serum sodium should be measured after 0,6,24, and 48 h of treatment with vaptans to prevent overly rapid correction of hyponatremia 4.
• Discontinuation of any vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse 4.
• The dosage of tolvaptan should be titrated carefully, especially in pediatric patients 5.