Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)


The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disorder with impaired water excretion (concentrated urine), caused by abnormal production of antidiuretic hormone (ADH) despite low serum osmolality.


  • 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



  • 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


  • 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.”

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