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, also called vasopressin) from the pituitary gland, leading to water retention and dilutional hyponatremia.

Definition and Pathophysiology

In SIADH, the body continues to release ADH despite low serum osmolality and normal or increased blood volume, which is physiologically inappropriate. This causes increased water reabsorption in the kidneys, resulting in concentrated urine and diluted blood sodium levels, typically below 135 mEq/L.

Causes and Risk Factors

Common causes include certain medications (like SSRIs, carbamazepine, and some chemotherapy agents), central nervous system disorders, pulmonary diseases (particularly small cell lung cancer), and post-surgical states, as noted in the study by 1.

Clinical Presentation

Patients may present with symptoms ranging from mild (headache, irritability, difficulty concentrating) to severe (confusion, seizures, coma) depending on the severity and rapidity of sodium decline.

Diagnosis

The condition is diagnosed based on laboratory findings of hyponatremia, decreased serum osmolality, inappropriately concentrated urine, and normal kidney, adrenal, and thyroid function, as outlined in the guidelines 1.

Management

Management includes treating the underlying cause, fluid restriction (typically 800-1000 mL/day), and in severe cases, administration of hypertonic saline. For chronic SIADH, medications like tolvaptan (a vasopressin receptor antagonist) or demeclocycline may be used to promote water excretion, as discussed in the study by 1. Some key points to consider in management include:

• The use of vaptans, such as tolvaptan, which have been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, including SIADH, as noted in the study by 1.
• The importance of monitoring serum sodium levels and adjusting treatment accordingly to avoid rapid corrections and potential complications, as highlighted in the guidelines by 1.
• The need for individualized treatment approaches, taking into account the underlying cause of SIADH, the severity of hyponatremia, and the patient's overall clinical condition, as emphasized in the study by 1.

From the FDA Drug Label

SAMSCA is a selective vasopressin V2-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)

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

• Key points:
  • SIADH is characterized by excessive ADH secretion
  • Leads to water retention and hyponatremia
  • Tolvaptan is indicated for the treatment of SIADH, among other conditions 2 No further information is provided in the drug label about the definition or causes of SIADH.

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 diseases, including lung and brain diseases, as well as the use of certain drugs such as chlorpropamide, carbamazepine, and diuretics 3, 4, 5, 7.
• The main groups of causes of SIADH include neoplasia, neurological diseases, lung diseases, and a wide variety of drugs 5, 7.

Diagnosis of SIADH

• Diagnosis of SIADH is confirmed by demonstrating a high urine osmolality with a low plasma osmolality, in the absence of diuretic use 3.
• The diagnosis should be considered if the five cardinal criteria are fulfilled: hypotonic hyponatraemia, natriuresis, urine osmolality in excess of plasma osmolality, absence of oedema and volume depletion, and normal renal and adrenal function 5.
• SIADH should be suspected in any patient with hyponatremia, hyposmolarity, urine osmolality above 100 mosmol/hgH2O, urine sodium concentration usually above 40 mEq/L, and clinical euvolemia 6.

Symptoms and Treatment of SIADH

• Symptoms of SIADH generally occur only when hyponatremia is severe (less than or equal to 125 meq/L) and may include anorexia, vomiting, and confusion, followed by seizures, coma, and death 3.
• Treatment of SIADH consists of elimination of underlying causes and restriction of fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated 3, 7.
• Fluid restriction is the recommended first-line treatment for mild or moderate hyponatremia, while etiologic treatment leads to the disappearance of SIADH 7.
• For symptomatic patients with chronic SIADH, the mainstay of therapy remains fluid restriction, and new antagonists to the antidiuretic action of AVP offer a new therapeutic approach 5.