Syndrome of inappropriate antidiuretic hormone secretion
Epidemiology
Etiology
Drugs
- Anticonvulsants (e.g., carbamazepine, valproate)
- Antidepressants
- SSRIs (e.g., sertraline)
- MAO inhibitors
- TCAs (e.g., amitriptyline)
- Chemotherapeutic agents
- Mitotic inhibitors (e.g., vincristine)
- Alkylating agents (e.g., cyclophosphamide, cisplatin)
Pathophysiology
- ↑ ADH secretion → receptor-mediated signaling cascade in the distal convoluted tubules and the collecting ducts of the kidneys → build-up of additional water canals (aquaporin-2) in the luminal cell membrane
- Water is drawn out of the urine and into the hyperosmolar kidney tissue → concentration of urine and ↑ Urine osmolality (becomes higher than serum osmolality)
- Water retention → ↓ serum osmolality with transient volume expansion → ↑ ANP, ↑ BNP, and ↓ aldosterone → ↑ urinary sodium and water excretion → normal extracellular fluid volume and low plasma osmolality (euvolemic hyponatremia)
- Osmotic fluid shifts → cerebral edema and ↑ intracranial pressure (may occur in patients with extremely low Na+ levels)
Clinical features
Symptoms of hyponatremia
- Mild
- Anorexia
- Nausea, vomiting
- Headache
- Muscle cramps
- Moderate
- Muscle weakness
- Lethargy
- Confusion
- Severe
- Seizures
- Altered consciousness
Tip
Both SIADH and Primary hyperaldosteronism have no edema. A hyponatremic patient with edema should raise suspicion for other conditions (e.g. congestive heart failure).