Diabetes Insipidus 

Diabetes insipidus (DI) may be central or nephrogenic. Central DI is characterized by decreased secretion of antidiuretic hormone (ADH)—also known as arginine vasopressin (AVP)—which gives rise to polyuria and polydipsia by diminishing the patient’s ability to concentrate urine.

Diminished or absent ADH can be the result of a defect in 1 or more sites involving the hypothalamic osmoreceptors, the supraoptic or paraventricular nuclei, or the supraopticohypophyseal tract. In contrast, lesions of the posterior pituitary rarely cause permanent diabetes insipidus, because ADH is produced in the hypothalamus and still can be secreted into the circulation.

Nephrogenic DI is characterized by a decrease in the ability to concentrate urine due to a resistance to ADH action in the kidney.^[1] Nephrogenic DI can be observed in chronic renal insufficiency, lithium toxicity, hypercalcemia, hypokalemia, and tubulointerstitial disease; rarely, diabetes insipidus may be hereditary.

Pharmacologic treatment of DI generally involves the use of desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]), nonhormonal drugs, or both. Patients must be instructed in simple principles of water balance to avoid dehydration and water intoxication (if not carefully monitoring water intake).

ADH is the primary determinant of free water excretion in the body. Its main target is the kidney, where it acts by altering the water permeability of the cortical and medullary collecting tubules. Water is reabsorbed by osmotic equilibration with the hypertonic interstitium and returned to the systemic circulation. The actions of ADH are mediated through at least 2 receptors: V1 mediates vasoconstriction, enhancement of corticotrophin release, and renal prostaglandin synthesis; V2 mediates the antidiuretic response.^{[2, 3]}

Diminished or absent ADH can be the result of a defect in 1 or more sites involving the hypothalamic osmoreceptors, the supraoptic or paraventricular nuclei, or the supraopticohypophyseal tract. In contrast, lesions of the posterior pituitary rarely cause permanent diabetes insipidus, because ADH is produced in the hypothalamus and still can be secreted into the circulation.

The literature indicates that 30% of DI cases are idiopathic, 25% are related to malignant or benign tumors of the brain or pituitary, 20% follow cranial surgery, and 16% are secondary to head trauma.

Idiopathic DI is associated with destruction of cells in the hypothalamus, often as part of an autoimmune process. This is characterized by lymphocytic infiltration of the stalk and posterior pituitary. Magnetic resonance imaging (MRI) may show abnormalities in these structures. The presence of antibodies directed against vasopressin cells may help to predict the development of central DI.

Primary intracranial tumors causing DI include craniopharyngioma or pineal tumors. The appearance of other hypothalamic manifestations may be delayed for as long as 10 years. Thus, periodic follow-up of patients diagnosed with idiopathic DI is necessary to detect slowly growing intracranial lesions.

The frequency with which DI develops after neurosurgery varies with the surgery’s scope. Approximately 10-20% of patients experience DI after transsphenoidal removal of an adenoma, compared with 60-80% of those who have undergone surgical removal of large tumors. Not all cases of DI are permanent. In a German study of metabolic disturbances after transsphenoidal pituitary adenoma surgery, only 8.7% of DI cases persisted for more than 3 months.^[4]

The most common causes of postoperative polyuria are excretion of excess fluid administered during surgery and an osmotic diuresis resulting from treatment for cerebral edema.^[5]

A prospective study in 436 patients who sustained severe head injury found that DI occurred in 15.4% of all such individuals.^[6]

Familial DI is rare. Almost 90% of hereditary cases of nephrogenic DI result from an X-linked defect of the AVP receptor 2 gene (AVPR2).^[7] A rare autosomal dominant variant results from the mutation of AQP2, an aquaporin gene that gives rise to a water channel that is expressed exclusively in the kidney’s collecting ducts.

Autosomal dominant central DI that involves mutations of the AVP - neurophysin gene has also been identified. Mutations reported to date involve the signal peptide region or, more commonly, neurophysin II.^[8] The mechanism by which the mutations impair AVP (ADH) release is not understood but may involve the accumulation of the ADH precursor, leading to the death of the ADH-producing cells.

Other causes of DI include cancer (eg, lung cancer, lymphoma, leukemia, hypoxic encephalopathy, infiltrative disorders (histiocytosis X, sarcoidosis, anorexia nervosa, and vascular lesions, such as arteriovenous malformations or aneurysms.

Diabetes insipidus is uncommon in the United States, with a prevalence of 1 case per 25,000 population. No significant sex differences in central or nephrogenic diabetes insipidus exist: male and female prevalences are equal.

The prognosis is generally excellent, depending upon the underlying illness. Mortality is rare in adults as long as water is available. Severe dehydration, hypernatremia, fever, cardiovascular collapse, and death can ensue in children, elderly people, or in those with complicating illnesses.