diabetes insipidus

diabetes insipidus, pathological endocrine condition characterized by excessive thirst and excessive production of very dilute urine. The disorder is caused by a lack of antidiuretic hormone (vasopressin) or a blocking of its action. This hormone, produced by the hypothalamus, regulates the kidney’s conservation of water and production of urine through its ability to stimulate reabsorption of water by the kidneys. Diabetes insipidus is so named because the large volume of urine that is excreted is tasteless, or “insipid,” rather than sweet, as is the case in diabetes mellitus, in which the urine may contain large quantities of glucose.

Types and causes

Diabetes insipidus may be caused by a deficiency of vasopressin secretion (central diabetes insipidus) or by a deficiency of vasopressin action in the kidney (nephrogenic diabetes insipidus). The form of the disorder that results from injury to the hypothalamic nucleus, which is the tract by which vasopressin is conveyed to the neurohypophysis (posterior lobe of the pituitary gland) for storage, is called central diabetes insipidus. This condition may be caused by trauma, such as brain or pituitary surgery, and diseases, such as brain tumours, pituitary tumours, or granulomatous infiltration (formation of grainlike lumps that are associated with certain diseases, including tuberculosis and sarcoidosis). When a result of trauma, the condition only occurs if about 90 percent or more of the neurohypophyseal system (in the posterior lobe of the pituitary gland) is destroyed. Central diabetes insipidus also can be caused by mutations in the genes encoding vasopressin and neurophysin (a protein synthesized by the hypothalamus) that result in decreased production of vasopressin. In some patients, however, no cause can be found, and the condition is called idiopathic central diabetes insipidus.

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Another form of the disease is called nephrogenic diabetes insipidus, which results when the supplies of vasopressin are adequate but the kidney tubules are unresponsive—either genetically or because of an acquired condition. The most severe form of this disorder is congenital hereditary nephrogenic diabetes insipidus. This condition is caused by mutations in a gene designated AVPR2 (arginine vasopressin receptor 2), which encodes a specific form of the vasopressin receptor, or by mutations in a gene known as AQP2 (aquaporin 2), which encodes a specific form of aquaporin. The vasopressin receptor gene AVPR2 is located on the X chromosome. As a result, affected males have notably more-severe diabetes insipidus than do females.

Acquired nephrogenic diabetes insipidus can occur in patients with electrolyte imbalances, such as high serum calcium concentrations or low serum potassium concentrations, in patients with kidney disease, and in patients taking lithium carbonate. Acquired nephrogenic diabetes insipidus is rarely severe, and patients have normal vasopressin secretion, making treatment with desmopressin (a chemically modified form of vasopressin) ineffective. Adequate fluid must be provided, although the volume needed can be minimized somewhat if salt intake is limited or a diuretic drug is administered.

Symptoms, diagnosis, and treatment

The symptoms of both forms of diabetes insipidus are similar and include excessive thirst and excretion of large volumes of urine—usually 3 to 6 litres each day, although up to 20 litres per day has been recorded. Water is the preferred fluid, and, if it or other fluid is freely available, patients remain well except for the inconvenience of frequent drinking and urination day and night. In the absence of a source of fluid, patients become increasingly thirsty and irritable and ultimately stuporous and comatose as a result of hyperosmolality and decreased extracellular fluid volume.

Diagnosis of central diabetes insipidus is based on the presence of high serum osmolality and low urine osmolality and on the results of a fluid deprivation test, with measurements of serum osmolality and urine output and urine osmolality when fluids are restricted. During a fluid deprivation test, patients with diabetes insipidus continue to excrete large volumes of urine, and administration of vasopressin causes a decrease in urine volume, an increase in urine osmolality, and a decrease in serum osmolality. In contrast, in nephrogenic diabetes insipidus there is no response to administration of vasopressin.

Central diabetes insipidus can be treated effectively using desmopressin, which can be given by nasal spray, tablet, or injection. Injections of vasopressin are ineffective for those with nephrogenic diabetes insipidus.