What is the diagnosis and treatment of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion?

From the Guidelines

SIADH should be managed with fluid restriction and pharmacologic interventions, such as vasopressin receptor antagonists, to correct hyponatremia and prevent severe complications, as recommended by expert opinion 1. The management of SIADH involves treating the underlying cause, fluid restriction to less than 1 L/day, and monitoring serum sodium levels.

• Key signs and symptoms of SIADH include hyponatremia, hypoosmolality, inappropriately high urine osmolality, and inappropriately high urinary sodium concentration.
• For acute symptomatic hyponatremia, 3% hypertonic saline may be administered at 1-2 mL/kg/hour with careful monitoring to avoid rapid correction (limit to 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome) 1.
• Pharmacologic options include demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) to correct hyponatremia.
• Regular monitoring of serum sodium, osmolality, and urine studies is essential for effective management, and the accuracy of a diagnostic algorithm for SIADH can approach 95% with the assessment of effective arterial blood volume and fractional excretion of urate 1.
• The use of vaptans, such as tolvaptan, has been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, including SIADH, with a response rate of 45-82% in patients treated for a short period of time (1 week to 1 month) 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)

• Tolvaptan is indicated for the treatment of SIADH.
• The drug is used to treat clinically significant hypervolemic and euvolemic hyponatremia, including patients with heart failure and SIADH 2.

From the Research

Definition and Diagnosis of SIADH

• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition where the body produces an excessive amount of antidiuretic hormone (ADH), leading to water retention and hyponatremia 3.
• The diagnosis of SIADH involves ascertaining the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements 3.

Treatment Options for SIADH

• Treatment options for SIADH include fluid restriction, hypertonic saline, urea, demeclocycline, and vasopressin receptor antagonists (vaptans) 3.
• Vaptans, such as tolvaptan, have been shown to be effective in treating SIADH-associated hyponatremia, with a lower risk of overcorrection and osmotic demyelination syndrome 4, 5.
• Low-dose tolvaptan (3.75-7.5mg) has been found to be effective in increasing serum sodium levels in patients with SIADH, with a recommended starting dose of 7.5mg or 3.75mg in high-risk patients 4.

Safety and Efficacy of Tolvaptan

• Tolvaptan has been found to be safe and effective in treating SIADH-associated hyponatremia, with minimal side effects such as increased thirst, dry mouth, and urination 4, 5.
• The use of tolvaptan in pediatric patients with SIADH has been reported to be safe and effective, although the dosage should be titrated carefully 6.
• The clinical efficacy of tolvaptan in SIADH is supported by good quality randomized, placebo-controlled clinical trials, although long-term safety data are still needed 7.

Management of SIADH

• Fluid restriction is often recommended as the first-line therapy for SIADH, but it may be ineffective or unfeasible in many patients 7.
• The use of bolus therapy with 3% hypertonic sodium chloride has been recommended for the management of acute hyponatremia, with a focus on the use of vasopressin-2 receptor antagonists such as tolvaptan 7.
• Close monitoring of serum sodium levels is essential in the management of SIADH, particularly when using vaptans, to prevent overcorrection and osmotic demyelination syndrome 3, 4.