Among the idiopathic forms of DI, there also exists a congenital hypothalamic DI, of which only a small number of familial cases have been described. The disorder is evident at an early age and persists throughout life owing to a developmental defect of the supraoptic and paraventricular nuclei with a hypoplastic posterior lobe of the pituitary. This defect has been related in some cases to a point mutation in the vasopressin-neurophysin-glycopeptide gene. It may be combined with other genetic disorders such as the syndrome of diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome), and with Friedreich ataxia.
Acquired idiopathic DI may occur at any age, most often in childhood or early adult life and more often in males, and by definition has no apparent cause. Other signs of hypothalamic or pituitary disease are lacking in 80 percent of such patients, but steps must be taken to exclude other disease processes by repeating endocrine and radiologic studies periodically. In some cases of idiopathic DI, there are serum antibodies that react with the supraoptic neurons, raising the question of an autoimmune disorder. In a few such instances, postmortem examination has disclosed a decreased number of neurons in the supraoptic and paraventricular nuclei. Also, anorexia nervosa is often associated with mild DI.
Finally, it should be mentioned that certain drugs used in neurologic practice—for example, carbamazepine— may be the cause of reversible DI (although excessive secretion of ADH is more common in relation to this drug). As mentioned earlier, lithium regularly causes DI, at serum concentration levels that are supratherapeutic or, at times, within the upper therapeutic range.
In all these conditions, the severity and permanence of the DI are determined by the nature of the lesion. In cases of acute onset, three phases have been delineated: first, a severe DI lasting days; then, as the neurohypophysis degenerates, a reduction in severity of DI or even hyponatremia from excessive release of stored ADH; and finally, a persistent pattern that is usually lifelong. The neurohypophyseal axons can regenerate, allowing for some degree of recovery after months or years.
Diagnosis of diabetes insipidus The diagnosis is suggested by the passage of large quantities of dilute urine accompanied by polydipsia and polyuria lasting throughout the night. The thirst mechanism and drinking usually prevent dehydration and hypovolemia, but if the patient is stuporous or the thirst mechanism is inoperative, severe dehydration and hypernatremia can occur, leading to coma, seizures, and death. In an unresponsive patient careful measurement of fluid output and input are needed to expose the disorder.
A low urine osmolality and specific gravity are found in DI, in conjunction with high serum osmolality and sodium values. Osmotic dehydration as a cause of the polydipsia–polyuria syndrome, such as occurs with the glycosuria of diabetes mellitus must, of course, be excluded. A period of 6 to 8 h of dehydration increases urinary osmolality in a person with normal kidneys and neurohypophysis; it is this change in urine concentration that is most useful in the differential diagnosis of polyuria, particularly in distinguishing compulsive water drinkers from those with DI. In water intoxication, urinary volume and serum electrolytes normalize with water restriction. Proof that the patient has a central cause of DI and not nephrogenic unresponsiveness to vasopressin is obtained by injecting 5 U of vasopressin subcutaneously; this will diminish urine output and increase urine osmolality when there is a central cause of DI. Diagnosis is also aided by the radioimmunoassay for plasma ADH; ADH is usually reduced to less than 1.0 pg/mL in patients with central DI (normal: 1.4 to 2.7 pg/mL).