Description

• 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 disorder, such as neoplasm, a pulmonary disorder, or CNS disease
• Synonym(s): syndrome of inappropriate secretion of ADH; syndrome of inappropriate antidiuresis

Epidemiology

Incidence

• Often found in the hospital setting, where incidence can be as high as 35%
• Predominant age: elderly
• Predominate sex: females > males

Prevalence
It is also prevalent in hospitalized perioperative patients in response to stress, hypotonic fluids, and drugs.

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 carcinoma
  • Lymphoma
  • Mesothelioma
  • Small cell carcinoma of the lung
  • Pancreatic carcinoma
  • Thymoma
• Pulmonary conditions:
  • Asthma/COPD/pneumothorax
  • Atelectasis
  • 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)
  • CNS lupus
  • Encephalitis
  • Epilepsy
  • Guillain-Barré syndrome
  • Intracranial surgery
  • Meningitis
  • Multiple sclerosis
• Nephrogenic/hereditary:
  • A gain of function mutation in the gene for vasopressin 2 receptors (V2R)
• Other:
  • Acute intermittent porphyria
  • Delirium tremens
  • HIV infection/AIDS
  • Rocky Mountain spotted fever

Genetics

• 10% of patients have an X-linked mutation of V2R.
• Polymorphisms in TRPV4 gene

Risk Factors

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

General Prevention

• Search for the cause, if unknown.
• Reduce/change medications, if drug-induced.
• Lifelong restriction of fluid intake

Commonly Associated Conditions

See “Etiology and Pathophysiology.”