Syndrome of inappropriate ADH

Background

Etiologies

• CNS: stroke, intracranial hemorrhage, infection, trauma, and psychosis
• Malignancy: ectopic ADH production by small cell carcinoma or, even more rarely, with other lung cancers, head-and-neck cancer, olfactory neuroblastoma, and extrapulmonary small cell carcinoma
• Medications: chlorpropamide, carbamazepine, oxcarbazepine, high-dose cyclophosphamide, SSRIs
  • Others: vincristine, cinblastine, cinorelbine, cisplatin, thiothixene, thioridazine, haloperidol, amitriptyline, MAO inhibitors, melphalan, ifosfamide, methotrexate, opiates, NSAIDs, interferon alpha, interferon gamma, sodium valproate, bromocriptine, lorcainide, amiodarone, ciprofloxacin, high-dose imatinib, and ecstasy
• Surgery, likely mediated by pain, but also specifically after transsphenoidal pituitary surgery
• Lung disease: pneumonia, occasionally also with asthma, atelectasis, respiratory failure, and pneumothorax
• Endocrinopathies: hypopituitarism and hypothyroidism
  • Also exogenous vasopressin, desmopressin, and oxytocin
• HIV
• Hereditary SIADH
• Idiopathy, more common in older patients though occasionally found later to be from occult malignancy

Differential Diagnosis

• Cerebral salt wasting
  • Mimics SIADH
  • Most commonly caused by subarachnoid hemorrhage
  • Cerebral salt wasting should have high-normal serum urea, low serum uric acid, high urine volume, high urine sodium, normal to orthostatic blood pressure, and low central venous pressure
  • Requires fluid resuscitation rather than restriction

Diagnostic Criteria

• Essential criteria:
  • Effective serum osmolality <275 mOsm/kg
  • Urine osmolality >100 mOsm/kg at some level of decreased effective osmolality
  • Clinical euvolaemia
  • Urine sodium concentration >30 mmol/l with normal dietary salt and water intake
  • Absence of adrenal, thyroid, pituitary or renal insufficiency
  • No recent use of diuretic agents
• Supplemental criteria
  • Serum uric acid <0.24 mmol/l (<4 mg/dl)
  • Serum urea <3.6 mmol/l (<21.6 mg/dl)
  • Failure to correct hyponatraemia after 0.9% saline infusion
  • Fractional sodium excretion >0.5%
  • Fractional urea excretion >55%
  • Fractional uric acid excretion >12%
  • Correction of hyponatraemia through fluid restriction