What are the risk factors for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Risk Factors for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The most significant risk factors for SIADH include malignancies (particularly small cell lung cancer), certain medications, pulmonary disorders, and neurological conditions that lead to inappropriate release of antidiuretic hormone. 1

Malignancy-Related Risk Factors

• Small cell lung cancer (SCLC): 10-45% of SCLC cases produce ADH, with 1-5% developing symptomatic SIADH 1
• Other lung cancers:
  • Squamous cell carcinoma (1% of cases) 1
  • Adenocarcinoma (1% of cases) 1
• Other malignancies:
  • Head and neck cancers (3% of cases) 2
  • Hepatocellular carcinoma (rare) 3
  • Various other tumors including hematologic malignancies, intrathoracic non-pulmonary cancers, gastrointestinal cancers, and genitourinary cancers 2

Medication-Related Risk Factors

• Chemotherapeutic agents:

  • Platinum-based chemotherapy (cisplatin) 1, 4
  • Vinca alkaloids (vincristine, vinblastine) 1, 2
  • Cyclophosphamide 2
  • Melphalan 2
  • Ifosfamide 1
  • Capecitabine 1
  • Topotecan 1

• Other medications:

  • Opioids 1
  • Non-steroidal anti-inflammatory drugs (NSAIDs) 1
  • Anticonvulsants 1, 4
  • Antidepressants 1
  • Chlorpropamide 4
  • Carbamazepine 4
  • Diuretics 4

Non-Malignant Medical Conditions

• Pulmonary disorders:

  • Infections 1, 5
  • Positive pressure ventilation 2
  • Conditions with decreased left atrial pressure 2

• Central nervous system disorders:

  • Brain trauma 1, 5
  • Stroke 1
  • Meningitis 1
  • Brain tumors 2
  • Encephalitis 5

Other Risk Factors

• Postoperative state 1, 5
• Pain 1
• Nausea 1
• Stress 1
• Hypovolemia 1
• Inappropriate infusion of hypotonic fluids (especially post-operatively) 5

Clinical Pearls and Pitfalls

• Hyponatremia in patients with SCLC is associated with shortened survival 1
• Early detection and management of SIADH can prevent severe hyponatremia, which can lead to seizures, coma, and death 1
• SIADH should be distinguished from cerebral salt wasting (CSW) in patients with neurological disorders, as the treatments are opposite (fluid restriction for SIADH vs. salt replacement for CSW) 6
• The diagnosis of SIADH requires exclusion of other causes of hyponatremia such as adrenal insufficiency 1
• Symptoms of hyponatremia can be nonspecific (confusion, headache, nausea), making prompt diagnosis difficult 1

Diagnostic Criteria for SIADH

For accurate diagnosis, all of the following criteria should be present:

• Hyponatremia (serum sodium < 134 mEq/L) 1
• Hypoosmolality (plasma osmolality < 275 mosm/kg) 1
• Inappropriately high urine osmolality (> 500 mosm/kg) 1
• Inappropriately high urinary sodium concentration (> 20 mEq/L) 1
• Absence of hypothyroidism, adrenal insufficiency, volume depletion, heart failure, cirrhosis, and hypothyroidism 1

Understanding these risk factors is essential for early identification and management of SIADH, which can significantly impact morbidity and mortality, particularly in cancer patients and those with neurological disorders.