What are the common causes of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

Common Causes of SIADH

SIADH results from four major categories: malignancies (especially small cell lung cancer), CNS disorders (infections, hemorrhage, trauma), medications (SSRIs, carbamazepine, chemotherapy agents), and pulmonary diseases. 1, 2

Malignancy-Related Causes

• Small cell lung cancer is the most common malignant cause of SIADH, occurring in 1-5% of cases 2
• Ectopic ADH production by tumor cells leads to inappropriate hormone secretion despite normal or low plasma osmolality 3, 4
• Other malignancies can also produce ectopic ADH, though less commonly than SCLC 4
• Treatment of the underlying malignancy often resolves the paraneoplastic SIADH 1

Central Nervous System Disorders

• CNS infections, space-occupying lesions (including abscesses), subarachnoid hemorrhage, and head trauma disrupt hypothalamic-pituitary function and cause SIADH 2, 5
• Brain abscesses present as ring-enhancing lesions on neuroimaging with surrounding edema and can trigger inappropriate ADH secretion through disruption of normal hypothalamic regulation 5
• Hyponatremia in subarachnoid hemorrhage patients is associated with higher rates of cerebral ischemia and worse outcomes at 3 months 1

Medication-Induced SIADH

• High-risk medications include SSRIs, carbamazepine, oxcarbazepine, NSAIDs, tramadol, and certain antipsychotics 1, 2
• Chemotherapeutic agents such as cisplatin, vinca alkaloids (vincristine, vinblastine), cyclophosphamide, and antiepileptic drugs like carbamazepine are well-documented causes 1
• Thiazide diuretics, particularly in older women, represent a major cause of hyponatremia in older adults 1
• The combination of thiazide diuretics with SSRIs or other SIADH-inducing medications substantially increases risk 1
• Opioids can also induce SIADH 1
• Discontinuing the offending medication is essential in treating drug-induced SIADH 1

Pulmonary Causes

• Lung diseases and inflammation are recognized causes, with malignancy being the most common pulmonary etiology 4
• Non-malignant pulmonary infections and inflammatory conditions can also trigger inappropriate ADH secretion 4

Post-Surgical and Iatrogenic Causes

• Post-surgical hyponatremia represents "appropriate" secretion of ADH with normovolemic hyponatremia and high mortality rates, requiring urgent treatment similar to SIADH 6
• SIADH following abdominal surgery is rare but documented, as seen after common bile duct exploration 7
• Hospitalization often worsens hyponatremia due to iatrogenic excess of oral and intravenous hypotonic fluids combined with reduced salt intake 6

Age-Related Risk Factors

• Old age is per se a risk factor for SIADH development 6
• Older patients, especially women, are at higher risk for medication-associated SIADH 1
• Aging is associated with increased sensitivity to hyponatremia due to age-related reduction in glomerular filtration rate 1

Critical Diagnostic Considerations

• SIADH is underdiagnosed in clinical practice 6
• The syndrome requires exclusion of hypothyroidism, adrenal insufficiency, volume depletion, renal failure, heart failure, and cirrhosis 2, 6
• Nonosmotic stimuli such as pain, nausea, and stress can override normal osmotic regulation and cause ADH excess 2

Common Pitfall to Avoid

• Confusing SIADH with cerebral salt wasting (CSW) in neurosurgical patients leads to incorrect treatment—SIADH requires fluid restriction while CSW requires volume and sodium replacement 2, 5