From the Guidelines
SIADH is a condition characterized by euvolemic hypoosmolar hyponatremia, where excess antidiuretic hormone (ADH) leads to water retention and dilutional hyponatremia, and its diagnosis and management are crucial to prevent severe complications such as seizures, coma, and death.
Definition and Pathophysiology
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) occurs when ADH continues to be released despite low serum osmolality, causing the kidneys to reabsorb water inappropriately, resulting in hyponatremia, as seen in approximately 10% to 45% of small cell lung cancer (SCLC) cases 1. The excess ADH activates vasopressin 2 receptors in renal tubules, leading to increased aquaporins and impaired free water clearance.
Clinical Presentation
Patients with SIADH typically present with symptoms of hyponatremia, such as general weakness, confusion, headache, and nausea, which can progress to life-threatening manifestations, including seizures and coma, if serum sodium levels drop below 120 mEq/L 1.
Diagnosis
Diagnosis of SIADH requires demonstrating hyponatremia with inappropriately concentrated urine, normal kidney function, and absence of volume depletion or edema, characterized by:
- 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
Treatment of SIADH focuses on addressing the underlying cause while managing hyponatremia through fluid restriction, typically less than 1 L/day, and other therapies such as hypertonic 3% saline IV for severe cases, and medications like demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) to correct hyponatremia. It is essential to avoid rapid correction of sodium levels to prevent osmotic demyelination syndrome, with correction rates generally limited to 8-10 mEq/L in 24 hours. Early detection and appropriate management of SIADH can prevent severe hyponatremia and improve patient outcomes, as hyponatremia in patients with SCLC is associated with shortened survival 1.
From the Research
Definition of SIADH
- The Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a disorder of water balance characterized by hypotonic hyponatremia and impaired water excretion 2.
- It is the most frequent underlying pathophysiology of hyponatraemia, which is the commonest electrolyte abnormality 3.
Diagnosis of SIADH
- The diagnosis of SIADH is based on the exclusion of other hyponatremic conditions, the presence of hyposmolality with inappropriate urine osmolality, and a urine sodium concentration usually above 30 mEq/L 2.
- Some simple and readily available biologic parameters, such as low urea and uric acid levels, can be helpful in the diagnosis of SIADH 2.
Treatment of SIADH
- Treatment options for SIADH include fluid restriction, demeclocycline, urea, frusemide, and saline infusion, all of which have their limitations 3.
- Demeclocycline has been used to treat chronic hyponatremia secondary to SIADH, but its use is not well defined and can differ between healthcare professionals 4.
- The introduction of vasopressin-2 receptor antagonists has allowed clinicians to specifically target the underlying pathophysiology of SIADH, but their cost may limit their use 5, 3.