Syndrome of inappropriate antidiuretic hormone secretion

Background

• Abbreviation: SIADH
• Inappropriate or continued action of ADH despite normal/increased plasma volume→ impaired water excretion→ hyponatremia and hypo-osmolality

Clinical Features

• See hyponatremia
• Symptoms of neoplasm, particularly lung neoplasm

Differential Diagnosis (Causes)

• Inappropriate or hypersecretion from hypothalamus
  • Infectious
    • Brain abscess
    • Encephalitis, meningitis
    • Rocky mountain spotted fever
    • Herpes Zoster
  • Vascular/hemorrhagic
    • Stroke, hypoxic ischemic encephalopathy, perinatal hypoxia
    • Cavernous sinus thrombosis
    • Subarachnoid hemorrhage
    • Subdural hematoma
  • Other
    • Acute intermittent porphyria
    • Cerebellar and cerebral atrophy
    • CNS lupus
    • Epilepsy, Delirium tremens
    • Multiple sclerosis, Guillain-Barré Syndrome
    • Hydrocephalus, ventriculoatrial shunt obstruction
    • Wernicke encephalopathy
    • Head trauma
• Ectopic ADH secretion due to neoplastic source
  • Lung carcinoma, mesothelioma
  • Duodenal, pancreatic, and colonic carcinomas
  • Adrenocortical, bladder/urothelial, ovarian, prostate, and cervical cancers
  • Brain tumor, leukemia/lymphoma, carcinoid, neuroblastoma, thymoma, Ewing's sarcoma
• Pulmonary disorders
• Drugs
  • ADH-stimulating
    • Acetylcholine, histamine
    • Antineoplastic agents - Adenine arabinoside, cyclophosphamide, ifosfamide, vincristine, vinblastine
    • Barbiturates, thiopental, MAOIs, tricyclic antidepressants
    • Opioids
    • Haloperidol, phenothiazines
    • Carbamazepine, oxcarbazepine
    • Halothane, nitrous oxide
    • Bromocriptine
    • Carbachol
  • Chlorpropamide
    • Isoproterenol
    • Nicotine
  • ADH-potentiating
    • Griseofulvin
    • Hypoglycemic agents – Metformin, phenformin, tolbutamide
    • Oxytocin (large doses)
    • Indomethacin, aspirin, NSAIDs
    • Theophylline
    • Vasopressin analogs (eg, AVP, DDAVP)

Evaluation

Essential Criteria

• Effective serum osmolality <275 mOsm/kg
• Urine specific gravity > 1.015
• Urine osmolality >100 mOsm/kg at some level of decreased effective osmolality
• Clinical euvolemia
• 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 (<4mg/dl)
• Serum urea <3.6 mmol/l (<21.6mg/dl)
• Failure to correct hyponatremia after 0.9% saline infusion
• Fractional sodium excretion >0.5%
• Fractional urea excretion >55%
• Fractional uric acid excretion >12%
• Correction of hyponatremia through fluid restriction

Management

• See hyponatremia
• Fluid restriction
• Oral salt tablets (NaCl) for mild-moderate hyponatremia
• 100 cc bolus of 3% NaCl for severe symptoms, repeat if neurologic symptoms persist or worsen
  • Ideally given through central line
• DO NOT give normal saline 0.9%
  • In SIADH, sodium handling is intact and renal system will excrete Na
  • Water handling out of balance from excessive ADH
  • All sodium will be excreted, urine osmolality will remain high
  • Half of the bolus of normal saline will be retained, worsening hyponatremia
• See osmotic demyelination syndrome for excessively rapid overcorrection

Disposition

• See hyponatremia