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Differential Diagnosis

The syndrome of inappropriate antidiuretic hormone is characterized by a hypersecretion of vasopressin relative to the patients serum osmolality and manifests as hypotonic (low serum osmolality<280 mEq/L) hyponatremia and impaired water excretion in euvolemic patients without cardiac, renal, thyroid or adrenal deficiencies. By definition, patients suffering from this disorder lack signs of hypervolemia (edema, hypertension or jugular venous distension) or hypovolemia (tachycardia, hypotension, orthostatic changes in vitals or oliguria). SIADH is the most commonly diagnosed etiology of hyponatremia among hospitalized patients.

Clinical manifestations of SIADH are induced by the resulting hyponatremia and include lethargy, muscle cramps, anorexia, nausea and vomiting. As hyponatremia worsens, coma, convulsions or death may occur. Lab abnormalities include hypotonic hyponatremia, variable but usually concentrated urine (urine osmolality greater than 100 mOsm/kg) with a random urinary sodium level above 20 mEq/L, and characteristically low levels of both BUN and uric acid.

A search for the underlying etiology should be undertaken once the condition is diagnosed and treatment started. Malignancies associated with SIADH may not be apparent at the time of diagnosis, so reevaluation with an ongoing malignancy work-up may take up to 12 months in order to establish the diagnosis.

Vasopressin receptor antagonists are effective as a therapeutic intervention. Severe symptomatic hyponatremia (seizures or coma) is an emergency requiring prompt treatment. In a patient with coma or seizures the risks of continued severe hyponatremia are far greater than the risks of rapid sodium correction, mainly central pontine myelinolysis. Treatment in these patients entails either vasopressin receptor antagonists or infusion of 3% saline at a rate of 0.1 ml/kg/min. The serum sodium should be monitored frequently during infusion and should not be corrected to levels greater than 10-12 mmol/L in a single 24 hour period. Chronic therapy entails water restriction with adequate dietary solute intake. Since many patients have problems adhering to a water restricted lifestyle, other therapeutic options include demeclocycline (300-600 mg orally BID), oral sodium bicarbonate tablets in conjunction with loop diuretics, or oral tolvaptan.