Non-Pharmacological Causes of SIADH
SIADH has three major non-pharmacological etiologic categories: malignancies (especially small cell lung cancer), central nervous system disorders, and pulmonary diseases. 1, 2
Malignant Causes
Small cell lung cancer (SCLC) is the most common malignant cause of SIADH, occurring in approximately 15% of SCLC patients (214 cases out of 1473 patients in large series). 3 This represents the single most frequent paraneoplastic cause of the syndrome. 2
Other malignancies associated with SIADH include:
- Head and neck cancers (3% incidence - 47 cases out of 1696 patients) 3
- Non-small cell lung cancer (0.7% incidence) 3
- Primary brain tumors 3
- Hematologic malignancies 3
- Gastrointestinal cancers, gynecological cancers, breast and prostatic cancer 3
- Sarcomas and skin tumors 3
The mechanism involves ectopic production of arginine vasopressin (AVP) by tumor cells, leading to persistent ADH secretion despite hyponatremia and low plasma osmolality. 2, 4
Central Nervous System Disorders
CNS pathology represents a major category of SIADH causes, with mechanisms involving disruption of hypothalamic-pituitary function. 2 Specific CNS causes include:
- Subarachnoid hemorrhage 2, 5
- Head trauma 2
- CNS infections (meningitis, encephalitis) 2
- Space-occupying lesions (tumors, abscesses) 2
- Stroke and other cerebrovascular events 4
A critical clinical pitfall: In neurosurgical patients, you must 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 Fluid restriction in CSW can be hazardous and worsen outcomes. 5
Pulmonary Disorders
Intrathoracic non-malignant conditions are well-established causes of SIADH through nonosmotic stimulation of AVP release. 2, 4 These include:
- Pneumonia and other pulmonary infections 4, 3
- Tuberculosis 4
- Positive pressure ventilation 3
- Acute respiratory failure 4
- Chronic obstructive pulmonary disease 4
Post-Operative State
Inappropriate infusion of hypotonic fluids in the post-operative period remains a common iatrogenic cause of SIADH. 4 The mechanism involves:
- Nonosmotic stimuli (pain, nausea, stress) override normal osmotic regulation and cause AVP excess 2, 4
- Surgical stress and anesthesia trigger inappropriate ADH release 4
- Hospital-acquired hyponatremia from hypotonic IV fluids affects 15-30% of hospitalized patients and is entirely preventable by using isotonic maintenance fluids 1
Other Non-Pharmacological Causes
Additional causes include:
- Acute pancreatitis - a well-established nonosmotic stimulus for AVP release 4
- Conditions with decreased left atrial pressure 3
- Hypothyroidism and adrenal insufficiency (though these must be excluded to diagnose SIADH) 4
Pathophysiologic Categories
SIADH can be classified into four patterns of osmoregulated AVP secretion: 4
- Erratic AVP release - random, unpredictable secretion 4
- Reset osmostat - AVP secretion occurs at a lower osmotic threshold 4
- Persistent AVP release at low plasma osmolality - continuous secretion despite hyponatremia 4
- Normal osmoregulated AVP secretion - appropriate regulation but with increased sensitivity 4
Clinical Context and Reversibility
For cancer patients with SIADH, 20-50% of delirium episodes can be reversed if the patient is not imminently dying. 6 Medication-induced delirium is usually reversible, whereas hypoxic encephalopathy and organ failure are associated with non-reversibility. 6
The optimal therapy for malignancy-related SIADH is treating the underlying cancer - hyponatremia usually improves after successful treatment of the underlying cause. 1, 3 If the disease becomes refractory, other treatment methods include water restriction, demeclocycline therapy, or in severe cases, hypertonic saline with furosemide during careful monitoring. 3