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

From the Guidelines

The diagnosis of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is based on laboratory findings of euvolemic hypoosmolar hyponatremia, characterized by low serum osmolality, inappropriately high urine osmolality, and elevated urinary sodium concentration, in the absence of diuretic treatment, adrenal insufficiency, heart failure, cirrhosis, and hypothyroidism. The diagnostic criteria for 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, as stated in the American College of Chest Physicians evidence-based clinical practice guidelines 1. The diagnosis of SIADH requires a thorough history and physical examination to identify potential causes, such as malignancies, CNS disorders, pulmonary diseases, or medications, and to exclude other causes of hyponatremia, such as diuretic use, hypothyroidism, adrenal insufficiency, and heart failure 1. Further investigation should focus on identifying the underlying cause to guide appropriate treatment, and laboratory findings such as urine osmolality of > 300 mosm/kg, urinary sodium level of > 40 mEq/L, serum osmolality of < 275 mosm/kg, and serum uric acid concentration of < 4 mg/dL can support the diagnosis of SIADH 1.

From the FDA Drug Label

Tolvaptan tablets are 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)

The diagnosis of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is not explicitly stated in the provided drug labels. However, it is mentioned as one of the underlying causes of euvolemic or hypervolemic hyponatremia, for which tolvaptan is indicated.

• Key points:
  • SIADH is associated with euvolemic or hypervolemic hyponatremia
  • Tolvaptan is used to treat hyponatremia, including SIADH
  • The exact diagnosis of SIADH is not provided in the drug labels 2, 2, 2

From the Research

Diagnosis of SIADH

The diagnosis of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is based on several key factors, including:

• Clinical euvolaemic state with low serum sodium and osmolality 3
• Raised urine sodium and osmolality 3, 4
• Exclusion of pseudohyponatraemia and diuretic use 3
• High urine osmolality (>500 mOsm/kg) 4
• Persistence of high urine sodium concentrations 4

Laboratory Measurements

Laboratory measurements play a crucial role in the diagnosis of SIADH, including:

• Urine sodium concentration: a value of 50 mEq/L is considered accurate in separating SIADH from hypovolemic hyponatremia 5
• Urine osmolality: high urine osmolality (>500 mOsm/kg) is indicative of SIADH 4
• Plasma osmolality: low plasma osmolality is a characteristic feature of SIADH 6

Clinical Evaluation

Clinical evaluation is essential in the diagnosis of SIADH, including:

• Assessment of euvolemic state: both clinically and by laboratory measurements 7
• Evaluation of symptoms: such as anorexia, vomiting, and confusion, followed by seizures, coma, and death 6
• Identification of underlying causes: such as medications, malignancy, pulmonary disease, or central nervous system disorders 3