Causes of SIADH
SIADH has four major categories of causes: malignancies (especially small cell lung cancer), neurological disorders, pulmonary diseases, and medications, with drug-induced SIADH being particularly common in hospitalized patients. 1, 2
Malignancies
Small cell lung cancer (SCLC) is the most common malignant cause, occurring in approximately 15% of SCLC patients (214 cases out of 1,473 patients), though biochemical abnormalities may be present in 30-50% of cases 1, 3. The tumor cells commonly produce vasopressin (ADH), leading to SIADH 1.
Other malignancies associated with SIADH include:
- Non-small cell lung cancer (0.7% incidence) 3
- Head and neck cancers (3% incidence - 47 cases out of 1,696 patients), including oral squamous cell carcinoma 3, 4
- Primary brain tumors 3
- Hematologic malignancies 3
- Gastrointestinal, gynecological, breast, and prostatic cancers (less common) 3
In SCLC patients with paraneoplastic SIADH, treatment of the underlying malignancy is important alongside hyponatremia management, and hyponatremia usually improves after successful treatment of the underlying cause 1.
Medications
Chemotherapeutic agents are a major drug-related cause, including:
Other medications that commonly induce SIADH include:
- Antidepressants (SSRIs) 1
- Antiepileptic drugs (particularly carbamazepine) 1
- NSAIDs 1
- Opioids 1
- Chlorpropamide 1
Discontinuing offending medications is essential in treating the underlying cause of SIADH 1.
Neurological Disorders
Central nervous system pathology is a well-established cause of SIADH 2. In neurosurgical patients, particularly those with subarachnoid hemorrhage, it is critical to distinguish SIADH from cerebral salt wasting (CSW), as they require opposite treatments - SIADH requires fluid restriction while CSW requires volume and sodium replacement 1, 5.
Hyponatremia in patients with subarachnoid hemorrhage is associated with higher rates of cerebral ischemia and worse outcomes at 3 months 1.
Pulmonary Diseases
Intrathoracic disorders are a major category of SIADH causes, including:
Post-Operative State
Inappropriate infusion of hypotonic fluids in the post-operative state remains a common iatrogenic cause of SIADH 2. Hypotonic fluids such as D5 water worsen hyponatremia by providing free water that cannot be properly excreted due to SIADH 1.
Other Causes
- Conditions with decreased left atrial pressure 3
- Idiopathic SIADH in cases where no obvious cause is identified despite thorough workup 6
Clinical Pitfall
Failing to recognize and treat the underlying cause is a common pitfall that should be avoided 1, 7. Where possible, all attempts should be made to identify and rectify the cause of SIADH, as effective treatment of the underlying condition is often the definitive solution for paraneoplastic SIADH 1, 5.