From the Guidelines
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is a condition characterized by euvolemic hypoosmolar hyponatremia, resulting from the excessive production of antidiuretic hormone (ADH), which leads to water retention and dilutional hyponatremia. This condition occurs when ADH continues to be released despite low serum osmolality, causing the kidneys to reabsorb excessive water and dilute the sodium concentration in the blood 1. The signs and symptoms of SIADH are determined by the degree of hyponatremia and the acuity of hypoosmolality, and can range from general weakness, confusion, headache, and nausea to life-threatening manifestations such as seizures and coma.
Key Characteristics of SIADH
- 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
Diagnosis and Management
Diagnosis of SIADH requires demonstrating hyponatremia with inappropriately concentrated urine, normal kidney function, and absence of volume depletion or edema 1. Treatment depends on the severity of the condition and includes free water restriction (< 1 L/d) as a first-line treatment of asymptomatic mild SIADH and a recommended adjunct to other therapy for severe cases. Hypertonic 3% saline IV is given in life-threatening or acute symptomatic and severe (< 120 mEq/L) hyponatremia. Demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) may also be used to correct hyponatremia 1.
Underlying Causes
Common causes of SIADH include certain cancers (particularly small cell lung cancer), central nervous system disorders, pulmonary diseases, and medications like SSRIs, carbamazepine, and certain chemotherapy agents. The underlying cause must be addressed whenever possible, as this may resolve the SIADH if the trigger can be eliminated.
From the Research
Definition of SIADH
- The Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is a condition where the body produces an excessive amount of antidiuretic hormone (ADH), leading to water retention and hyponatremia (low sodium levels in the blood) 2, 3, 4, 5, 6.
- SIADH is often caused by various disorders, including malignancy, pulmonary, or neurologic disorders, and can lead to euvolemic hyponatremia 2, 6.
Diagnosis and Treatment of SIADH
- The diagnosis of SIADH requires a structured assessment of essential and supplemental criteria, including euvolemia, inappropriately concentrated urine, and exclusion of other causes of hyponatremia 6.
- Treatment options for SIADH include fluid restriction, hypertonic saline, demeclocyclin, and vasopressin receptor antagonists such as tolvaptan 2, 3, 4, 5, 6.
- Tolvaptan has been shown to be effective in correcting hyponatremia in patients with SIADH, with a lower risk of overcorrection and improved efficacy compared to fluid restriction 2, 3, 4, 5.
Efficacy and Safety of Tolvaptan
- Studies have demonstrated the efficacy and safety of tolvaptan in patients with SIADH, with significant improvements in serum sodium levels and minimal side effects 2, 3, 4, 5.
- However, tolvaptan may be associated with a higher risk of sodium overcorrection and polyuria, highlighting the need for careful monitoring and dose adjustment 2, 3, 4.
- The optimal dose of tolvaptan for treating SIADH remains unclear, with studies suggesting that lower doses (e.g., 7.5 mg) may be effective and safer than higher doses (e.g., 15 mg) 2, 3, 4.