Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Description

• Decreased urinary electrolyte-free water excretion leads to dilutional hyponatremia (total body sodium [Na] levels may be normal or near-normal, but the patient’s total body water is increased).
• Often secondary to medications but may be associated with an underlying pulmonary disorder or central nervous system (CNS) disease
• Common cause of hyponatremia in hospitalized patients
• Synonym(s): SIADH; syndrome of inappropriate antidiuresis

Epidemiology

Incidence

• Often found in the hospital setting, especially perioperative patients in response to stress, intravenous fluids, and drugs; the incidence can be as high as 35%.
• Predominant age: elderly
• Predominate sex: females > males

Etiology and Pathophysiology

• Drugs:
  • Antidepressants (e.g., SSRIs, tricyclics, monoamine oxidase inhibitors [MAOIs])
  • Antineoplastic drugs (e.g., vincristine, vinblastine, cisplatin, cyclophosphamide)
  • Antipsychotic agents (e.g., risperidone, quetiapine, phenothiazines, haloperidol)
  • Analgesics (e.g., duloxetine, pregabalin, tramadol, NSAIDs)
  • Anticonvulsants (e.g., carbamazepine, oxcarbazepine, valproic acid, phenytoin)
  • Others (e.g., vasopressin, DDAVP, oxytocin, ciprofloxacin, α-interferon, ecstasy)
• Malignancies (ectopic ADH production):
  • Bronchogenic or small cell carcinoma of the lung
  • Lymphoma
  • Mesothelioma
  • Pancreatic adenocarcinoma
  • Thymoma
• Pulmonary conditions:
  • Asthma/COPD
  • Atelectasis/pneumothorax
  • Cystic fibrosis
  • Positive pressure mechanical ventilation
  • Pneumonia (viral, bacterial)
  • Pulmonary tuberculosis (TB)
  • Sarcoidosis
• Neurologic causes:
  • Brain tumor
  • CNS injury (i.e., subarachnoid hemorrhage, trauma, stroke, surgery)
  • CNS lupus
  • Encephalitis, meningitis
  • Epilepsy
  • Guillain-Barré syndrome
  • Multiple sclerosis
• Acute intermittent porphyria
• Delirium tremens
• HIV infection/AIDS
• Rocky Mountain spotted fever

Genetics

• 10% of patients have an X-linked mutation of vasopressin V2 receptor (V2R).
• Polymorphisms in TRPV4 gene

Risk Factors

• Advanced age
• Postoperative status
• Institutionalization
• Use of predisposing drugs

General Prevention

Avoid high-risk medications, if drug induced.

Commonly Associated Conditions

See “Etiology and Pathophysiology.”