Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

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Basics

Description

  • A syndrome of abnormal production of antidiuretic hormone (ADH), despite low serum osmolality, leading to hyponatremia and inappropriately elevated urine 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, 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

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
    • Atelectasis
    • Cystic fibrosis
    • Positive pressure mechanical ventilation
    • Pneumonia
    • Pulmonary tuberculosis (TB)
    • Sarcoidosis
  • Neurologic causes:
    • Brain tumor
    • CNS injury (i.e., SAH, trauma, stroke)
    • CNS lupus
    • Encephalitis
    • Epilepsy
    • Guillain-Barré syndrome
    • Intracranial surgery
    • Meningitis
    • Multiple sclerosis
  • Other:
    • Acute intermittent porphyria
    • Delirium tremens
    • HIV infection/AIDS
    • Rocky Mountain spotted fever
  • Idiopathic

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

Risk Factors

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

General Prevention

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

Commonly Associated Conditions

See “Etiology and Pathophysiology.”

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Basics

Description

  • A syndrome of abnormal production of antidiuretic hormone (ADH), despite low serum osmolality, leading to hyponatremia and inappropriately elevated urine 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, 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

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
    • Atelectasis
    • Cystic fibrosis
    • Positive pressure mechanical ventilation
    • Pneumonia
    • Pulmonary tuberculosis (TB)
    • Sarcoidosis
  • Neurologic causes:
    • Brain tumor
    • CNS injury (i.e., SAH, trauma, stroke)
    • CNS lupus
    • Encephalitis
    • Epilepsy
    • Guillain-Barré syndrome
    • Intracranial surgery
    • Meningitis
    • Multiple sclerosis
  • Other:
    • Acute intermittent porphyria
    • Delirium tremens
    • HIV infection/AIDS
    • Rocky Mountain spotted fever
  • Idiopathic

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

Risk Factors

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

General Prevention

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

Commonly Associated Conditions

See “Etiology and Pathophysiology.”

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