Causes of SIADH
The most common causes of SIADH are malignancy (particularly small cell lung cancer), medications (especially SSRIs, carbamazepine, and chemotherapy agents), pulmonary disorders, and central nervous system pathology. 1
Malignancy-Related SIADH
Small cell lung cancer (SCLC) is the most frequent malignant cause, occurring in approximately 10-45% of SCLC cases, though only 1-5% develop symptomatic SIADH. 1 The tumor cells directly produce arginine vasopressin (ADH), creating a paraneoplastic syndrome. 1 Hyponatremia in SCLC patients is associated with shortened survival, making early detection critical. 1
- Non-small cell lung cancer can also cause SIADH in approximately 0.7% of cases, with both squamous cell carcinoma and adenocarcinoma capable of producing ADH. 1
Medication-Induced SIADH
Multiple drug classes are well-established causes through stimulation of inappropriate ADH release: 1
Chemotherapy Agents
- Platinum-based chemotherapy (cisplatin), vinca alkaloids (vincristine, vinblastine), cyclophosphamide, and melphalan 2, 1
Psychotropic Medications
- SSRIs and SNRIs are major culprits, particularly in older adults 2, 1
- Carbamazepine and oxcarbazepine have moderate to high level evidence for causing SIADH 2
- Antipsychotics can induce SIADH, though the risk is more spread out over time compared to antidepressants 3
- Tramadol was added to the list of drugs associated with SIADH in recent updates 2
Other Medications
- NSAIDs and opioids 2, 1
- Thiazide diuretics, especially when combined with SSRIs or other SIADH-inducing medications 2
- Chlorpropamide 2
Critical pitfall: The concurrent use of multiple CNS agents or combining thiazide diuretics with SIADH-inducing medications substantially increases risk. 2, 1
Pulmonary Disorders
Non-malignant pulmonary conditions are important causes, including: 1
- Pneumonia
- Tuberculosis
- Other pulmonary infections
Central Nervous System Pathology
CNS disorders cause SIADH through disruption of normal hypothalamic-pituitary function and ADH regulation: 1
- CNS infections (meningitis, encephalitis)
- Space-occupying lesions (tumors, abscesses)
- Subarachnoid hemorrhage
- Head trauma
- Other neurological diseases
Neuroimaging with CT or MRI is essential to identify structural lesions such as ring-enhancing abscesses with surrounding edema. 1
Diagnostic Approach to Identify the Cause
Exclude Mimics First
Before diagnosing SIADH, you must exclude: 1
- Adrenal insufficiency
- Hypothyroidism
- Diuretic use
Confirm SIADH Diagnosis
The diagnosis requires: 2
- Hyponatremia (serum sodium < 134 mEq/L)
- Hypoosmolality (plasma osmolality < 275 mosm/kg)
- Inappropriately high urine osmolality (> 500 mosm/kg)
- Inappropriately high urinary sodium concentration (> 20 mEq/L)
- Absence of volume depletion
Distinguish from Cerebral Salt Wasting
SIADH must be distinguished from cerebral salt wasting (CSW), particularly in neurosurgical patients, as they require opposite management approaches. 1
- A serum uric acid level <4 mg/dL in the presence of hyponatremia has a positive predictive value for SIADH of 73-100% 2, 1
- Central venous pressure (CVP) can help: SIADH shows CVP 6-10 cm H₂O versus CSW with CVP <6 cm H₂O 2
Systematic Evaluation for Underlying Cause
Review all medications thoroughly - look for SSRIs, carbamazepine, chemotherapy agents, NSAIDs, opioids, and thiazide diuretics 2, 1
Obtain chest imaging - chest X-ray or CT to evaluate for lung cancer (especially SCLC) or pulmonary infections 1
Perform neuroimaging - CT or MRI of the brain if CNS pathology is suspected 1
Consider malignancy workup - particularly if patient has risk factors for lung cancer or unexplained weight loss 1
Critical pitfall: Failing to recognize and treat the underlying cause should be avoided, as hyponatremia usually improves after successful treatment of the underlying cause. 2