By Sheena Howson, MD

2/18/2011
SIADH
Inappropriate secretion of ADH
Water excretion is impaired
Suppression of ADH is impaired
Functions of ADH
Increases permeability of water in the cells of the distal
tubules by upregulating Aquaporin-2 channels (V2
receptors)
Increases the permeability of collecting ducts to urea
Increases SVR via IP3/Ca++ 2nd messengers on endothelium
CNS effects like memory formation and circadian rhythm
SIADH - causes
Intracranial – infection, stroke, hemorrhage, tumor, very common in
SAH population (69%)
Intrathoracic – malignancy, abscess, PNA, effusion, PTX, chest wall
deformity
Drugs – vasopressin, DDAVP, oxytocin, analgesics, antidepressants,
amiodarone, antipsychotics, sulfonylureas, carbamazepine,
cyclophosphamide
Extracranial tumors – small-cell lung CA, pancreatic CA
HIV/AIDS
Hereditary – “gain-of-function” V2 receptor mutation
Miscellaneous – Guillan-Barre, nausea, stress, pain, acute psychosis
Major surgery ****
Idiopathic
SIADH
Hypothalamus receives
feedback from:

• Osmoreceptors
• Aortic arch baroreceptors
• Carotid baroreceptors
• Atrial stretch receptors

Any increase in osmolality or

decrease in blood volume will
stimulate ADH secretion from
posterior pituitary.
SIADH - pathophysiology
ADH-induced water retention
Dilutional hyponatremia
Volume expansion -> secondary natriuresis
Sodium and water loss
Potassium loss
Result: Euvolemic hyponatremia
Reduced serum osmolality
Increased urine osmolality
Increased urine sodium
SIADH - diagnosis
Laboratory Findings
Na < 135 mEq/L
Posm < 270 mOsm/kg
Uosm > 300 mOsm/kg
UNa > 25 mEq/L
Low BUN
Normal Cr
Low uric acid
Low albumin
SIADH - treatment
Treat the underlying cause, if known
Fluid Restriction – commonly 800-1000mL/d
Correct Na+ deficit – no more than 10mEq/L in 24 hours,
18mEq/L in 48 hours
0.9% NaCl
3% NaCl
NaCl enteral tablets – 2-3g TID
Add a loop diuretic
SIADH – treatment
Vasopressin receptor antagonists
Promote aquaresis
Tolvaptan, conivaptan
 Vaprisol (Conivaptan)
 Indicated in euvolemic or hypervolemic hyponatremia

 Contraindicated in hypovolemic hyponatremia

 V1a and V2 receptors

 Causes aquaresis or excretion of free water

Demeclocycline or Lithium (diminished collecting

tubule response to ADH)
Cerebral Salt Wasting
Hyponatremia caused by impaired renal tubular function
-> inability of kidneys to conserve salt
Salt wasting leads to volume depletion
Two theories:
Impaired sympathetic neural input -> failure of aldosterone
release -> no sodium resorption
BNP release decreases sodium resorption, inhibits
renin/aldosterone release, decreases autonomic outflow at
level of brainstem
Cerebral Salt Wasting
Commonly occurs in subarachnoid hemorrhage
population (7%)
Carcinomatous, infectious meningitis
Encephalitis
Poliomyelitis
CNS tumors
CNS surgery – usually within the first 10 days
Cerebral Salt Wasting
Diagnosis:
Evidence of volume depletion
Increased urine output
Laboratory Findings
Na < 135 mEq/L
Low Posm
Uosm > 300 mOsm/kg
UNa > 40 mEq/L
High BUN
Increased Cr
Low uric acid
Increased albumin
Cerebral Salt Wasting
Treat with volume repletion
0.9% NaCl
3% NaCl is sometimes warranted
Fludrocortisone
Diabetes Insipidus
The most common cause of hypernatremia in
neurological population
Deficient ADH
Central DI – occurs with hypothalamic-pituitary axis
dysfunction or injury
Nephrogenic DI – diminished renal sensitivity to ADH
Usually considered a euvolemic to hypovolemic state,
depending on the patient’s thirst mechanism
Diabetes Insipidus
Diabetes Insipidus
Typical Clinical picture:
Polyuria
Polydipsia Laboratory Findings
Nocturia Na >145 mEq/L
Posm > 285 mOsm/kg
Uosm < 300 mOsm/kg
UNa low
Urine Spec. Grav. < 1.005
UOP > 3ml/kg/h
Diabetes Insipidus
Goal is to restore plasma volume and serum Na+ levels
Patient with intact thirst mechanism
 Pitcher at bedside. Drink to thirst only!
Severe forms
 Replace UOP 1:1 with 1/2NS
 DDAVP 5u SQ Q4-6h, commonly given orally/nasally

 DDAVP will be ineffective if nephrogenic (HCTZ can be used)

Review
SIADH CSW DI
Serum Na+ < 135 mEq/L < 135 mEq/L > 145 mEq/L
Urine Na+ > 25 mEq/L > 40 mEq/L < 25 mEq/L
Serum Osm < 270 mOsm/kg < 270 mOsm/kg > 285 mOsm/kg
Urine Osm > 300 mOsm/kg > 300 mOsm/kg < 300 mOsm/kg
Urine O/P oliguria polyuria polyuria
CVP normal/high low normal/low
Plasma ADH high normal low
Rx Fluid restrict, give Give volume, give Drink to thirst,
Na+, vaprisol, Na+, DDAVP (central),
demeclocycline fludrocortisone HCTZ (nephrogenic)