Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)



  • Most common cause of hyponatremia occurring in up to 15–30% of hospitalized patients (and significantly increases patient mortality in some studies)
  • A water balance problem more than one of sodium (Na) balance
  • Normal regulation of water balance:
    • Antidiuretic hormone (ADH):
      • Integral controller of water balance
      • Increases water permeability of the collecting tubules, resulting in free water reabsorption
      • Synthesized by hypothalamus but secreted by posterior pituitary gland
    • Water deprivation (increased plasma osmolality) stimulates secretion as sensed by:
      • Osmoreceptors/atrial stretch receptors
      • Carotid baroreceptors
      • Aortic arch/pulmonary veins
  • Hyponatremia:
    • Mild: Serum sodium <135 mEq/L
    • Moderate: Serum sodium <130 mEq/L
    • Severe: Serum sodium <125 mEq/L
    • Excess extracellular water relative to Na
    • Depletional hyponatremia:
      • Sodium depletion can be caused by diet, GI losses, diuretic use, and renal or adrenal disease
      • Often accompanied by extracellular fluid volume depletion
      • Hyponatremia associated with clinical signs of hypovolemia
      • Increased Hct, BUN, Cr
      • Urinary sodium excretion <20 mEq/L
    • Dilutional hyponatremia:
      • Increased extracellular water in the presence of normal or increased total body sodium
      • Can be caused by increased fluid intake (oral, IV), drugs, or medical conditions
      • Euvolemia with edema
      • Normal or decreased Hct, BUN, Cr
      • Urinary sodium excretion >20 mEq/L
      • Inappropriate ADH secretion is a form of dilutional hyponatremia
  • Definition of SIADH:
    • ADH secretion in the absence of hyperosmolality or hypovolemia leading to inappropriate elevation of arginine vasopressin (AVP) causing stimulation of aquaporins, and reabsorption of water from renal tubules
  • Criteria for definition:
    • Essential features:
      • Plasma osmolality of <270 mOsm/kg
      • Evidence of inappropriate urinary concentration (UOsm >100 mOsm/kg of water)
      • Clinical euvolemia (no evidence of volume overload or depletion)
      • Elevated plasma Na (>30 mmol/L) with normal salt intake
      • Absence of concomitant hypoadrenalism, hypothyroidism, or renal dysfunction
      • No recent diuretic use
    • Supplemental features:
      • Plasma uric acid <4 mg/dL
      • BUN <10 mg/dL
      • FENa >1%
      • Failure to correct hyponatremia after an infusion of normal saline (NS) 0.9%
      • Abnormal water load test (inability to excrete ≥90% of a 20 mL/kg water load in 4 hr)


Malignant Disorders
  • ADH-producing tumors
  • Cancer (small-cell lung, pancreatic, prostate)
  • Pituitary tumors
  • Thymoma
  • Lymphoma

Pulmonary Disorders
  • Infections (pneumonia/TB/lung abscess)
  • Mechanical dysfunction (COPD/PPV)

CNS Disorders
  • Mass lesions (tumor/abscess/subdural hematoma)
  • Inflammation (meningitis/encephalitis)
  • Demyelination (multiple sclerosis/Guillain–Barré)
  • Subarachnoid hemorrhage
  • Traumatic brain injury
  • Acute psychosis
  • CVA

  • Stimulators of AVP release (nicotine, TCAs, phenothiazines)
  • Altering renal function (DDAVP, oxytocin, vasopressin, prostaglandin synthesis inhibitors – NSAIDs)
  • ACE inhibitors and thiazides, especially in combination
  • Chlorpropamide
  • Vincristine
  • Anticonvulsants (carbamazepine, oxcarbazepine)
  • Antidepressants (Trazadone, Mirtazapine, Venlafaxine, SSRIs)
  • Antipsychotics (with higher risk associated with first generation drugs)
  • Ecstasy (MDMA)

  • Endurance exercise
  • General anesthesia
  • Pain
  • Stress

  • Often multifactorial
  • Hereditary
  • Idiopathic

May be underdiagnosed in psychiatric patients due to:
  • Symptoms can mimic underlying psychiatric conditions
  • Many psychiatric conditions (i.e., schizophrenic polydipsia, compulsive drinking behaviors, anorexia-related water loading) and medications precipitating SIADH (see Medications under Etiology)

Cerebral salt-wasting syndrome (CSWS) can mimic SIADH
  • Seen in patients with cerebral tumors or subarachnoid hemorrhage and in neurosurgical patients
  • Etiology unclear
  • Represents appropriate water resorption in the face of salt wasting (urine Na >30–40 mmol/L)
  • Fluid restriction can help differentiate the 2:
    • In SIADH: Hypouricemia will correct
    • In CSWS: Hypouricemia will persist
  • Treatment of CSWS may differ from that of SIADH:
    • Infusion of NS
    • May benefit from fludrocortisones therapy

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