SIADH, DI, Cerebral Salt Wasting By Tracy Merrill MD Feb 24, 2003

SIADH: = Syndrome of Inappropriate ADH Secretion Definition: levels of ADH are inappropriately elevated compared to body’s low osmolality, and ADH levels are not suppressed by further decreases in blood osmolality.

SIADH: causes Irritation of CNS: meningitis, encephalitis, brain tumors, brain hemorrhage, hypoxic insult, trauma, brain abscess, Guillain Barre, hydrocephalus Pulmonary disorders: pneumonia, asthma, positive end expiratory pressure ventilation, CF, TB, pneumothorax

SIADH: causes continued Drugs: vincristine, vinblastine, opiates, carbamazepime, cyclophosphamide Unregulated tumor production of ADH-like peptides: oat cell lung carcinoma for example, Ewings sarcoma, carcinoma of duodenum, pancreas, thymus

SIADH: function of ADH = antidiuretic hormone = vasopressin ADH is made in the supra-optic nuclei in the hypothalamus, stored in the posterior pituitary Normally released into the bloodstream when osmo-receptors detect high plasma osmolality At the kidney, attaches to receptors in the collecting ducts, opens up water channels Water is passively reabsorbed along the kidney’s medullary concentration gradient

SIADH: signs and symptoms Decreased/low urine output Signs of hyponatremia: lethargy, apathy, disorientation, muscle cramps, anorexia, agitation Signs of water toxicity: nausea, vomiting, personality changes, confused, combative If Na < 110 mEq/L, seizures, bulbar palsies, hypothermia, stupor, coma

SIADH: lab values Serum Na < 135 (Na is diluted by excessive free water re-absorption) Serum osmolality low, normal is ~ 270 Urine Na is inappropriately high, >20 mmol/L, actually losing Na in urine instead of retaining it Urine osmolality is inappropriately high, can range b/t 300-1400 mosm/L CVP is high from free water retention

SIADH: treatment Fluid restriction, ¾ maintenance If symptomatic, may actually need to replace NaCl, can use hypertonic saline for example: 300cc/m2 of 1 ½ % NS Diuretics such as lasix Treat underlying disorder, for example usually resolves after removal of lung carcinomas

SIADH: treatment cont… Demeclochlorotetracycline, blocks ADH receptors in the renal collecting ducts In severe cases, hemodialysis Warning, if increase Na too fast, at risk for pontine myelinolysis Max correction of 15mEq in 24 hours

DI = Diabetes Insipidus Definition: inability to effectively conserve urinary water Central: ADH not made or not released in the hypothalamic-pituitary axis Nephrogenic: ADH is released but not detected by the receptors in the kidney collecting ducts, often a sex-linked recessive condition, also due to renal pathology, electrolyte disorders, drugs

Central DI: causes Head trauma Brain neoplasms Congenital CNS defects CNS infections CNS hypoxia ADH secretion also decreased by certain drugs: EtOh, demerol, MSO4, dilantin, barbiturates, glucocorticoids

DI: Make sure distinguish DI from conditions in which the presence of non-absorbable, osmotically active solutes in the renal tubules prevent water re-absorption. Example: glucose loss in the urine of diabetics will decrease the tubule- medullary concentration gradient and even though ADH is there, water won’t get passively reabsorbed

Central DI: signs/symptoms Polyuria Dehydration, may not be readily apparent b/c of hyper-osmolarity, fluid shifts from cells to intravascular spaces and maintains blood pressure, CVP Weight loss is a better measure of fluid status

Central DI: Lab values Hypernatremia, Na >150-160 High serum osmolality (normal 270) Urine Na < 20 mmol/L Low urine osmolality (very dilute urine)

Central DI: treatment Increase po or IV free H20 consumption, use hypotonic saline Volume replacement cc for cc Vasopressin/ ADH administration (bolus or drip 1.5-2.5 mU/kg/hr) Of course, treat underlying cause

Cerebral Salt Wasting Causes: CNS damage Closed head injury CNS surgery CNS tumors CNS infections, meningitis

Cerebral Salt Wasting Signs/symptoms: Polyuria Wt loss Dehydration/hypovolemia Hypotension Low CVP

Cerebral Salt Wasting Lab values: Hyponatremia due to excessive renal Na loss High urine Na, > 20 mmol/L Increased plasma ANP, atrial natriuretic peptide, b/c of low volume status Inappropriately normal or low aldosterone and ADH levels despite high ANP

Cerebral Salt Wasting Treatment: Volume for volume replacement of urine Na losses When dc’d from hospital, most will still need oral Na supplementation for a period of time

DI SIADH CSW CVP Urine Output polyuric decreased Serum Na high low Urine Na Serum osm Can be low or normal Urine osm CVP Can be normal or low