Treatment of diabetes insipidus A long-acting analogue of arginine vasopressin (desmopressin [DDAVP]) administered by nasal insufflation (10 to 20 mg or 0.1 to 0.2 mL) is the most commonly used treatment to control chronic DI. Vasopressin tannate in oil and a synthetic vasopressin nasal spray have also been used. The nasal form of DDAVP is generally preferred because of its long antidiuretic action and few side effects. In unconscious patients, aqueous vasopressin, 5 to 10 U given subcutaneously, is effective for 3 to 6 h; DDAVP, 1 to 4 mg subcutaneously, is effective for 12 to 24 h (in rare, critical situations, these drugs are given intravenously). The brief duration of action of the medication is advantageous in postoperative states and after head injury, for it allows the recognition of recovery of neurohypophyseal function and the avoidance of water intoxication. In the unconscious patient, great care must be taken in the acute stages to replace the fluid lost in the urine, but not to the point of water intoxication. These problems can be avoided by matching the amount of intravenous fluids to the urinary volume and by evaluating serum and urine osmolalities every 8 to 12 h. For patients with partial preservation of ADH function, chlorpropamide, clofibrate, or carbamazepine can be used to stimulate release of the hormone.
Syndrome of Inappropriate Antidiuretic
As described above, blood volume and osmolality are normally maintained within narrow limits by the secretion of ADH and the thirst mechanism. A reduction in osmolality of even 1 percent stimulates osmoreceptors in the hypothalamus to decrease ADH and to suppress thirst and drinking; increased osmolality and reduced blood volume do the opposite. Normally, blood osmolality is about 282 mmol/kg and is maintained within a very narrow range. Release of ADH begins when osmolality reaches 287 mmol/kg (the “osmotic threshold”). At this point, plasma ADH levels are 2 pg/mL and increase rapidly as the osmolality rises. The response of ADH secretion to hyperosmolality is not the same for all plasma solutes; in contrast to hypernatremia, for example, hyperosmolality induced by elevations in urea nitrogen or endogenous glucose produce minimal or no elevations in ADH.
Derangement of this delicately regulated mechanism, taking the form of dilutional hyponatremia and water retention without edema, is observed under a variety of clinical circumstances in which the plasma ADH is above normal or inappropriately normal despite plasma hypoosmolality. The term syndrome of inappropriate antidiuretic hormone (SIADH) was applied to this syndrome by Schwartz and Bartter because of its similarity to that produced in animals by the chronic administration of ADH. The same syndrome can arise from ectopic production of the hormone by tumor tissue. In such cases, the thirst mechanism is not inhibited by decreased osmolality, continued drinking further increases blood volume and reduces its solute concentration, and ADH levels are found to be persistently elevated. The physiologic hallmarks of this condition are concentrated urine, usually with an osmolality above 300 mOsm/L, and low serum osmolality and sodium concentrations. Because of the dilutional effects, the concentrations of urea nitrogen and uric acid are reduced in the blood and serve as markers for excessive total body water. Tissue edema is not seen because sodium excretion in the urine is maintained by suppression of the renin–angiotensin system and by increased atrial natriuretic peptide secretion (see below).