What is Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion?

From the Guidelines

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion is a condition characterized by excessive release of antidiuretic hormone (ADH), leading to water retention and dilutional hyponatremia, typically diagnosed by finding hyponatremia with inappropriately concentrated urine and elevated urine sodium, and managed by treating the underlying cause, fluid restriction, and in severe cases, administration of hypertonic saline or vasopressin receptor antagonists. The condition is often associated with certain medications, central nervous system disorders, pulmonary diseases, and post-surgical states, and can present with symptoms ranging from mild to severe, depending on the severity and rapidity of sodium decline 1. Key characteristics of SIADH include:

• 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 1. Management of SIADH is based on expert opinion, and recommended treatments include free water restriction (< 1 L/d) as a first-line treatment, and hypertonic 3% saline IV for life-threatening or acute symptomatic and severe hyponatremia, as well as demeclocycline, lithium, and vasopressin 2 receptor antagonists in certain cases 1. It is essential to distinguish SIADH from other causes of hyponatremia, such as paraneoplastic hyponatremia secondary to elevated atrial natriuretic peptide, and to assess the effective arterial blood volume with the fractional excretion of urate to improve the accuracy of the diagnostic algorithm for SIADH 1.

From the FDA Drug Label

Tolvaptan tablets are a selective vasopressin V 2-receptor antagonist 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)

resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others)

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion is a condition where there is an excessive release of antidiuretic hormone (ADH), leading to water retention and resulting in hyponatremia (low sodium levels in the blood).

• It is one of the underlying causes of euvolemic or hypervolemic hyponatremia.
• Tolvaptan is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH 2, 2.

From the Research

Definition and Causes of SIADH

• The Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion is a disorder characterized by the excessive release of antidiuretic hormone (ADH), leading to water retention and hyponatremia 3, 4, 5, 6, 7.
• SIADH can result from various causes, including neoplasia, neurological diseases, lung diseases, and the use of certain drugs such as chlorpropamide, carbamazepine, diuretics, and antineoplastic agents 3, 5, 6.
• The syndrome is often associated with hypotonic hyponatremia, natriuresis, urine osmolality in excess of plasma osmolality, absence of edema and volume depletion, and normal renal and adrenal function 5.

Clinical Features and Diagnosis

• The clinical features of SIADH are primarily neuro-muscular and gastro-intestinal, with symptoms such as anorexia, vomiting, confusion, seizures, coma, and death in severe cases 3, 5, 7.
• Diagnosis of SIADH is confirmed by demonstrating a high urine osmolality with a low plasma osmolality, in the absence of diuretic use, and by excluding other hormonal or hemodynamic disorders that can increase vasopressin or impair urinary dilution 3, 5, 6, 7.
• The five cardinal criteria for diagnosing SIADH include hypotonic hyponatremia, natriuresis, urine osmolality in excess of plasma osmolality, absence of edema and volume depletion, and normal renal and adrenal function 5.

Treatment and Management

• Treatment of SIADH consists of eliminating the underlying cause and restricting fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated 3, 5, 6, 7.
• Fluid restriction is the mainstay of therapy for symptomatic patients with chronic SIADH, while new antagonists to the antidiuretic action of ADH offer a new therapeutic approach 5.
• Other treatment modalities include infusion of hypertonic saline, administration of drugs that block the antidiuretic effect of vasopressin, and the use of urea, lithium, phenytoin, and loop diuretics, although their efficacy is limited 3, 4, 6, 7.
• The rate of correction of hyponatremia is dependent upon the degree of hyponatremia and the presence or absence of symptoms, with patients with severe neurological symptoms requiring prompt correction 4, 7.