Causes of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion
The main causes of SIADH include malignancies (especially small cell lung cancer), central nervous system disorders, pulmonary diseases, medications, and post-surgical states. 1
Major Categories of SIADH Causes
1. Malignancies
- Small cell lung cancer (10-45% of SIADH cases) 1
- Other tumors that can produce ADH:
- Head and neck cancers
- Brain tumors
- Pancreatic carcinoma
- Prostate cancer
- Lymphomas
2. Central Nervous System Disorders
- Stroke
- Intracranial hemorrhage
- Traumatic brain injury 2
- Meningitis
- Encephalitis
- Brain abscess
- Brain tumors
3. Pulmonary Diseases
- Pneumonia
- Tuberculosis
- Asthma
- COPD
- Acute respiratory failure
- Positive pressure ventilation
4. Medications
- Antidepressants:
- SSRIs
- SNRIs
- MAOIs
- Tricyclic antidepressants
- Antipsychotics
- Anticonvulsants:
- Carbamazepine 3
- Valproate
- Diuretics (especially thiazides)
- NSAIDs
- Opioids
- Chemotherapeutic agents
- Immunosuppressants
5. Other Causes
- Post-surgical state
- Pain
- Nausea
- HIV infection
- Idiopathic (no identifiable cause)
- Hereditary (rare genetic mutations)
Pathophysiological Mechanisms
SIADH develops due to persistent elevated plasma arginine vasopressin (AVP) concentrations despite hyponatremia and plasma hypo-osmolality 4. Four patterns of abnormal osmoregulation have been identified:
- Erratic AVP release
- Reset osmostat (altered threshold for AVP release)
- Persistent AVP release at low plasma osmolality
- Normal osmoregulated AVP secretion with abnormal thirst regulation
Clinical Implications
When evaluating a patient with suspected SIADH, it's essential to:
- Perform thorough medication review, as many drugs can induce SIADH 1
- Consider chest imaging to rule out small cell lung cancer, which is a common cause 1
- Evaluate for neurological disorders, particularly in patients with recent head trauma or neurological symptoms
- Distinguish SIADH from other causes of hyponatremia, particularly cerebral salt wasting (CSW), as treatment approaches differ significantly 1
Diagnostic Approach
The diagnosis of SIADH requires all of the following criteria:
- Hyponatremia (serum sodium <134 mEq/L)
- Plasma hypoosmolality (<275 mOsm/kg)
- Inappropriately high urine osmolality (>500 mOsm/kg)
- Elevated urinary sodium concentration (>20 mEq/L)
- Clinical euvolemia
- Normal thyroid and adrenal function 1
Management Considerations
Treatment should be directed at the underlying cause while managing hyponatremia. Fluid restriction (1,000-1,500 mL/day) is the mainstay of therapy for chronic SIADH 1. For medication-induced SIADH, discontinuation of the offending agent should be considered when possible.
For persistent or severe cases, pharmacological options include:
- Vasopressin receptor antagonists (tolvaptan)
- Demeclocycline
- Urea
Correction of serum sodium should not exceed 8-10 mmol/L per day to avoid osmotic demyelination syndrome 1.