From the Guidelines
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is a condition where there is excessive release of antidiuretic hormone (ADH, also called vasopressin) from the posterior pituitary gland despite normal or low serum osmolality, leading to water retention, dilutional hyponatremia, and concentrated urine. The pathophysiology of SIADH involves the excess ADH causing increased water reabsorption in the renal collecting ducts through aquaporin-2 water channels, resulting in water retention and dilutional hyponatremia (serum sodium typically below 135 mEq/L) 1. Common causes of SIADH include certain medications (carbamazepine, SSRIs, opioids), malignancies (particularly small cell lung cancer), CNS disorders (meningitis, stroke), pulmonary diseases (pneumonia, tuberculosis), and post-surgical states. The classic findings of SIADH include:
- Hyponatremia with inappropriately concentrated urine (urine osmolality >100 mOsm/kg)
- Elevated urine sodium (typically >40 mEq/L)
- Normal kidney, adrenal, and thyroid function
- Absence of edema or volume depletion Treatment of SIADH focuses on addressing the underlying cause while managing fluid restriction (typically 800-1000 mL/day), and in severe cases may require hypertonic saline, loop diuretics, or vasopressin receptor antagonists like tolvaptan 1. The most effective treatment for SIADH is the use of vaptans, which are selective antagonists of the V2-receptors of arginine-vasopressin in the principal cells of the collecting ducts, enhancing solute-free water excretion and improving serum sodium concentration 1. It is essential to note that the safety of vaptans has only been established for short-term treatments lasting from one week to one month, and long-term use may be associated with increased mortality rates 1. In clinical practice, several vaptans are available, including conivaptan, lixivaptan, and tolvaptan, which can be used intravenously or orally 1. Overall, the management of SIADH requires a comprehensive approach, including diagnosis, treatment of the underlying cause, and careful monitoring of serum sodium levels to prevent complications such as seizures, coma, and death 1.
From the Research
SIADH Pathophysiology
- 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 2, 3.
- The pathophysiology of SIADH involves the excessive secretion of ADH, which binds to vasopressin receptors in the kidneys, increasing water reabsorption and leading to hyponatremia 3, 4.
- The underlying causes of SIADH can be neurologic disorders, neurosurgical procedures, or other conditions that stimulate the excessive production of ADH 2, 5.
Treatment Options
- Traditional treatment options for SIADH include fluid restriction, sodium repletion, and diuretics, but these may not address the underlying pathophysiology of excess ADH secretion 2, 3.
- Vasopressin-receptor antagonists, such as conivaptan and tolvaptan, have been shown to be effective in treating SIADH-induced hyponatremia by blocking the action of ADH on the kidneys 2, 3, 4, 5, 6.
- Conivaptan is an intravenous vasopressin-receptor antagonist that has been used to treat euvolemic and hypervolemic hyponatremia in adults, while tolvaptan is an oral vasopressin V2-receptor antagonist that induces free water excretion without increasing sodium excretion 2, 3, 4, 6.
Clinical Evidence
- Studies have shown that conivaptan and tolvaptan can safely and effectively correct hyponatremia in patients with SIADH, with significant increases in serum sodium levels observed within 24 hours of treatment 2, 3, 4, 6.
- Long-term low-dose tolvaptan has been shown to be safe and effective in treating SIADH, with no cases of overcorrection or significant side effects reported 4.
- The use of vaptans in neurocritically ill patients has been associated with a significant increase in serum sodium levels, but also carries a risk of sodium overcorrection and hypotension 6.