Syndrome Of Inappropriate Antidiuretic Hormone Secretion (Siadh)

Basics

Description

  • Most common cause of hyponatremia occurring in up to 15–30% of hospitalized patients (and increases patient mortality in some studies)
  • 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 due to diet, GI losses, diuretic use, renal/adrenal disease often accompanies extracellular fluid volume depletion
      • Increased Hct, BUN, Cr
      • Urinary sodium excretion <20 mEq/L
    • Dilutional hyponatremia:
      • Increased extracellular water with 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
  • Definition of syndrome of inappropriate antidiuretic hormone secretion (SIADH):
    • ADH secretion without hyperosmolality or hypovolemia leads to inappropriate elevation of arginine vasopressin (AVP), causing stimulation of aquaporins/water reabsorption
    • SIADH is a form of dilutional hyponatremia
  • Criteria for definition:
    • Essential features:
      • Plasma osmolality of <270 mOsm/kg
      • Urine Osm >100 mOsm/kg of water
      • Clinical euvolemia
      • 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)

Etiology

Malignant Disorders

  • Cancer (small-cell lung, pancreatic, prostate, lymphoma)
  • Tumors (pituitary, thymoma, ADH secreting)

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)
  • TBI and stroke (hemorrhagic and ischemic)
  • Acute psychosis (see Alert below)

Medications

  • Stimulators of AVP release (nicotine, TCAs, phenothiazines):
    • Altering renal function (DDAVP, oxytocin, vasopressin, NSAIDs)
  • ACE inhibitors and thiazides, especially in combination
  • Anticonvulsants (carbamazepine, oxcarbazepine)
  • Antidepressants (TCAs, trazadone, mirtazapine, venlafaxine, SSRIs)
  • Antipsychotics (1st generation are highest risk)
  • Others (vincristine, ecstasy [MDMA])

Transient

  • Endurance exercise, general anesthesia, pain/stress
  • Initiation/induction of:
    • Chemotherapy (prostate cancer)
    • Puberty/fertility suppression (transgender care)
    • Medical manipulation of hypopituitary axis

Other

  • Often multifactorial (hereditary, HIV/AIDS, idiopathic)
ALERT

May be underdiagnosed in psychiatric patients due to:

  • Mimicking underlying psychiatric conditions
  • Many psychiatric conditions and medications can precipitate SIADH (ie, schizophrenic polydipsia, compulsive drinking behaviors, anorexia-related water loading, see Medications under Etiology)
ALERT

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 fludrocortisone therapy

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