This is a disease in which there is a lack of antidiuretic hormone (ADH) effect secondary to either a lack of the hormones secretion or due to a lack of effect of the hormone on the renal tubles. ADH (also known as vasopressin) serves to increase the permeability to water of the cortical collecting tubules and the collecting ducts thus increasing the body's water conservation mechanism. This increased permeability allows the kidney to conserve body water and concentrate the urine. A lack of ADH or renal tubule resistance to the action of ADH results in an inability of the kidney to conserve total body water, the production of a large quantity of dilute urine (anywhere from 3 to 20 liters per day), and , if the individual is deprived of water or has an impaired thirst mechanism, severe dehydration with resultant hypernatremia. Therefore, the most common symptoms of diabetes insipidus include polyuria, thirst and polydipsia.

The lab abnormalities most commonly encountered are a mild hypernatremia, an elevated serum osmolality, a low urine osmolality, hyposthenuria (low urine specific gravity) on urinalysis testing, and hyperuricemia, which is encountered in patients with the nephrogenic variety of this disorder. Because most patients with this disorder retain some ability, albeit reduced, to secrete ADH, urine volume may be quite variable depending on the severity of the disease. Patients who do retain the ability to produce small quantities of ADH still excrete dilute urine despite the increased sensitivity of the renal tubules to the effect of ADH. The reason for the reduction in maximum urinary concentrating capacity is believed to be secondary to washout of the renal medullary concentration gradient as a result of the chronic polyuria.

Neurogenic or central diabetes insipidus results when the posterior pituitary no longer secretes or secretes inadequate amounts of ADH. In this disorder, the kidney tubules still respond to ADH, and in fact, are often quite sensitive to the presence of this hormone. The most common causes include head trauma, neurosurgery, brain tumors (especially pituitary adenomas and crainiopharyngiomas) and idiopathic disease.  DDAVP, either intranasal or oral form, is an effective therapy.

Nephrogenic diabetes insipidus is the result of an impaired renal response to ADH and occurs in the presence of hypercalcemia, hypokalemia, osmotic diuresis, protein malnutrition, chronic renal failure or as a hereditary defect in renal water conservation. There are two forms of nephrogenic diabetes insipidus:

Type I:  In this disorder, renal resistance is complete. Urinary concentrating capacity is impaired despite the presence of even increased levels of ADH.

Type II:  Partial renal resistance to ADH is the pathology. Urinary concentration will occur in the presence of elevated levels of serum ADH (usually at levels 20 times normal) produced either by prolonged water deprivation or administration of exogenous vasopressin (DDAVP) at a standard diagnostic dose (0.05-0.1U/kg.).