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

From the Guidelines

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should be managed with fluid restriction and pharmacologic options such as vasopressin receptor antagonists, with the goal of correcting hyponatremia and preventing severe complications. The management of SIADH involves treating the underlying cause, fluid restriction to less than 1 L/day, and monitoring serum sodium levels 1. For acute symptomatic hyponatremia, 3% hypertonic saline may be administered with careful monitoring to avoid rapid correction (limit to 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome) 1. Some key points to consider in the management of SIADH include:

• Fluid restriction to less than 1 L/day as a first-line treatment for asymptomatic mild SIADH and as an adjunct to other therapy for severe cases 1
• Use of pharmacologic options such as demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) to correct hyponatremia 1
• Administration of hypertonic 3% saline IV in life-threatening or acute symptomatic and severe (< 120 mEq/L) hyponatremia 1
• Monitoring of serum sodium levels and careful assessment of the patient's volume status to guide treatment 1
• Consideration of the underlying cause of SIADH, such as small cell lung cancer, and treatment of the underlying condition 1 It is also important to note that the treatment of SIADH should be individualized based on the patient's specific needs and circumstances, and that careful monitoring and adjustment of treatment are necessary to prevent complications such as osmotic demyelination syndrome 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 label states that tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH 2, 2, and 2.

• Key points:
  • Tolvaptan is used to treat SIADH.
  • The treatment is for clinically significant hypervolemic and euvolemic hyponatremia.
  • Tolvaptan is not for use in patients with autosomal dominant polycystic kidney disease (ADPKD) outside of the FDA-approved REMS.
  • Patients requiring urgent intervention to raise serum sodium should not be treated with tolvaptan tablets.

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.
• SIADH accounts for approximately one-third of all cases of hyponatremia, and its diagnosis requires ascertaining a 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 increasing serum sodium levels in patients with SIADH, with a lower risk of overcorrection and osmotic demyelination syndrome 4, 5, 6.
• 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, with minimal side effects of increased thirst, dry mouth, and urination 4, 6.
• The use of tolvaptan in pediatric patients with SIADH has been reported to be safe and effective, although the dosage should be titrated carefully 7.
• Tolvaptan has been found to improve the physical component of the SF-12 Health Survey in patients with SIADH, and to reduce the incidence of fluid restriction 6.

Management of SIADH

• The management of SIADH requires careful monitoring of serum sodium levels, particularly during the first 24 hours of treatment with vaptans 3.
• The daily increase of serum sodium should be limited to less than 8-10 mmol/liter to prevent osmotic demyelination syndrome 3.
• Discontinuation of vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse, and may require tapering of the vaptan dose or restriction of fluid intake 3.