Diabetes insipidus (DI) is a rare disease that occurs when the body’s precise system of regulating the kidneys’ handling of fluids is disrupted, causing frequent urination.

The body has a complex system for balancing the volume and composition of body fluids. The kidneys remove extra body fluids from the bloodstream. These fluids are stored in the bladder as urine. If the fluid regulation system is working properly, the kidneys make less urine to conserve fluid when water intake is decreased or water is lost, for example, through sweating or diarrhea.

With DI, the large volume of urine is diluted, mostly water. To make up for lost water, a person with DI may feel the need to drink large amounts and is likely to urinate frequently, even at night, which can disrupt sleep and, on occasion, cause bedwetting. Because of the excretion of abnormally large volumes of dilute urine, people with DI may quickly become dehydrated if they do not drink enough water. Children with DI may be irritable or listless and may have fever, vomiting, or diarrhea.

Diabetes insipidus should not be confused with diabetes mellitus (DM), which results from insulin deficiency or resistance leading to high blood glucose, also called blood sugar. DI and DM are unrelated, although they can have similar signs and symptoms, like excessive thirst and excessive urination. DI is a different form of illness altogether.

Milder forms of DI can be managed by drinking enough water, usually between 2 and 2.5 liters a day. DI severe enough to endanger a person’s health is rare.

Central DI results from damage to the pituitary gland, which disrupts the normal storage and release of ADH – antidiuretic hormone that directs the kidneys to reabsorb water into the bloodstream and make less urine. Damage to the pituitary gland can be caused by different diseases as well as by head injuries, neurosurgery, or genetic disorders.

To treat the ADH deficiency that results from any kind of damage to the hypothalamus or pituitary, a synthetic hormone called desmopressin can be taken by an injection, a nasal spray, or a pill.

Nephrogenic DI results when the kidneys are unable to respond to ADH. The kidneys’ ability to respond to ADH can be impaired by drugs and by chronic disorders including polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders. Sometimes the cause of nephrogenic DI is never discovered.

A person with nephrogenic DI may be given hydrochlorothiazide (HCTZ) or indomethacin. HCTZ is sometimes combined with another drug called amiloride. The combination of HCTZ and amiloride is sold under the brand name Moduretic.

Dipsogenic DI is caused by a defect in or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output.

Scientists have not yet found an effective treatment for dipsogenic DI.

Gestational DI occurs only during pregnancy and results when an enzyme made by the placenta destroys ADH in the mother.

Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.