Cancers That Cause Paraneoplastic SIADH
Small cell lung cancer (SCLC) is the predominant malignancy causing paraneoplastic SIADH, accounting for the vast majority of cases, while non-small cell lung cancer and other malignancies cause SIADH much less frequently. 1
Primary Malignancies Associated with SIADH
Lung Cancer (Most Common)
Small Cell Lung Cancer (SCLC)
- SCLC is by far the most common cancer causing paraneoplastic SIADH, with 10-45% of SCLC cases producing arginine vasopressin (ADH), though only 1-5% develop symptomatic SIADH 1
- SCLC cells have neuroendocrine features that enable ectopic ADH production, making this the most frequent endocrine paraneoplastic syndrome in SCLC 2
- Biochemical evidence of elevated ADH is present in approximately 38% of SCLC patients, even when clinically asymptomatic 3
- The hyponatremia associated with SCLC-related SIADH is linked to shortened survival 1
Non-Small Cell Lung Cancer (NSCLC)
- NSCLC causes paraneoplastic SIADH in only approximately 1% of cases, making it significantly less common than SCLC 1, 2
- Both squamous cell carcinoma and adenocarcinoma subtypes of NSCLC have been reported to cause SIADH, though this remains rare 1, 4
Hematologic Malignancies
Myelodysplastic Syndrome
- Myelodysplastic syndrome with blast crisis has been documented to cause SIADH, though this is an uncommon association 5
- In these patients, SIADH should be considered in the differential diagnosis of hyponatremia 5
Clinical Significance and Management Implications
Recognition of the underlying malignancy is critical because treatment of the cancer is the definitive therapy for paraneoplastic SIADH 1, 2
- Hyponatremia typically improves after successful treatment of the underlying SCLC with chemotherapy 2
- Early detection and appropriate management can prevent severe hyponatremia leading to seizures, coma, and death 1
- In SCLC patients, the presence of SIADH may serve as a tumor marker, with plasma ADH levels potentially useful for monitoring disease status 3
Important Diagnostic Considerations
When evaluating for paraneoplastic SIADH, the diagnosis requires:
- Hyponatremia (serum sodium < 134 mEq/L) 1, 6
- Hypoosmolality (plasma osmolality < 275 mosm/kg) 1, 6
- Inappropriately high urine osmolality (> 500 mosm/kg) 1, 6
- Inappropriately high urinary sodium concentration (> 20 mEq/L) 1, 6
- Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1, 6
A serum uric acid level < 4 mg/dL in the presence of hyponatremia has a positive predictive value for SIADH of 73-100% 6, 7
Common Pitfall to Avoid
Do not overlook dual paraneoplastic syndromes in SCLC patients. SCLC can simultaneously produce both ADH and ACTH, causing both SIADH and ectopic Cushing syndrome 8, 9. The SIADH may be masked or underdiagnosed when ectopic ACTH syndrome is present, as cortisol and ADH have antagonistic effects on renal sodium excretion 9. Always evaluate for both syndromes when one is identified, as this affects prognosis and treatment planning 2, 8.