Diabetes insipidus

Definition

Diabetes insipidus (DI) is a disorder that causes the patient to produce excessive quantities of urine. The massively increased urine output is usually accompanied by intense thirst.

Description

Diabetes insipidus is usually the result of the body's inability to appropriately produce, store or release a hormone that increases water absorption by the kidneys and decreases urine flow. The balance of fluid within the body is maintained through a number of mechanisms. One important chemical involved in fluid balance is called antidiuretic hormone (ADH). ADH is produced by the pituitary, a small gland located at the base of the brain. In a healthy person and under normal conditions, ADH is continuously released. ADH influences the amount of fluid that the kidneys reabsorb into the circulatory system and the amount of fluid that the kidneys pass out of the body in the form of urine.

Production of ADH is regulated by the osmolality of the circulating blood. Osmolality refers to the concentration of dissolved chemicals (such as sodium, potassium, and chloride; together called solute) circulating in the fluid base of the blood (plasma). When there is very little fluid compared to the concentration of solute, the pituitary will increase ADH production. This tells the kidneys to retain more water and to decrease the amount of urine produced. As fluid is retained, the concentration of solute will normalize. At other times, when the fluid content of the blood is high in comparison to the concentration of solute, ADH production will decrease. The kidneys are then free to pass an increased amount of fluid out of the body in the urine. Again, this will allow the plasma osmolality to return to normal.

Diabetes insipidus occurs when either the amount of ADH produced by the pituitary is below normal, commonly referred to as central diabetes insipidus (central DI), or the kidney's ability to respond to ADH is defective, known as nephrogenic diabetes insipidus (nephrogenic DI). In either case, a person with DI will pass extraordinarily large quantities of urine, sometimes reaching 10 or more liters each day. At the same time, the patient's blood will be very highly concentrated, with low fluid volume and high concentrations of solute.

DI occurs on average when a person is about 24 years old, and occurs more frequently in males than in females.

Causes and symptoms

Central diabetes insipidus is damage to the pituitary gland or hypothalamus due to:

• inflammation or injury to the head
• brain surgery
• cancers that have spread to the pituitary gland (most commonly occurring with breast cancer)
• sarcoidosis (or other related disorders), causing destruction of the pituitary gland
• illness such as meningitis
• a tumor
• infection

Central DI may also occur in women who are pregnant or have just given birth, and in patients with AIDS who have suffered certain types of brain infections. In some cases of central diabetes insipidus the cause is unknown.

Nephrogenic diabetes insipidus results when there is a problem in the kidneys tubules, the mechanisms that trigger the excretion or reabsorption of water. When this defect occurs, the kidneys are unable to respond to ADH appropriately. The defect may be caused by:

• a chronic kidney disorder
• an inherited genetic disorder
• high levels of calcium in the body (hypercalcemia)
• the use of drugs such as lithium and tetracycline

In approximately one in four patients with nephrogenic DI, the cause is undetermined.

Symptoms of DI include extreme thirst and the production of tremendous quantities of diluted urine. Other symptoms include bed wetting and the increased urge to urinate during the night. Patients with DI typically drink huge amounts of water, and usually report a specific craving for cold water. When the amount of water passed in the urine exceeds the patient's ability to drink ample replacement water, the patient may begin to suffer from symptoms of dehydration. These symptoms include weakness, fatigue, fever, low blood pressure, increased heart rate, dizziness, and confusion. If left untreated, the patient could lapse into unconsciousness and die.

Diagnosis

Diagnosis should be suspected in any patient with sudden increased thirst and urination. Laboratory examination of urine will reveal very dilute urine, made up mostly of water with no solute. Examination of the blood will reveal very concentrated blood, high in solute and low in fluid volume.

A water deprivation test may be performed. This test requires a patient to stop all fluid intake. The patient is weighed just before the test begins, and urine is collected and examined hourly. The test is stopped when:

• the patient has lost more than 5% of his or her original body weight
• the patient has reached certain limits of low blood pressure and increased heart rate
• the urine is no longer changing significantly from one sample to the next in terms of solute concentration

The next step of the test involves injecting a synthetic form of ADH, with one last urine sample examined 60 minutes later. Comparing plasma and urine osmolality allows the doctor to diagnose either central DI, nephrogenic DI, partial DI, or psychogenic polydipsia.

KEY TERMS

Concentration —Refers to the amount of solute present in a solution, compared to the total amount of solvent.

Dilute —A solution that has comparatively more fluid in it, relative to the quantity of solute.

Osmolality —A measure of the solute-to-solvent concentration of a solution.

Solute —Solid substances that are dissolved in liquid in order to make a solution.

Treatment

Treatment is determined based on the form of the condition. For central DI treatment may include:

• the medication desmopressin, a synthetic antidiuretic hormone that may be taken orally, by injection or as a nasal spray
• in less severe cases of central DI, increased water intake may be the primary treatment option

Treatment for nephrogenic DI may include:

• a low-salt diet to reduce the amount of urine produced by the kidneys
• drinking the appropriate amount of water to avoid dehydration
• the medicine hydrochlorothiazide, a diuretic, may be prescribed alone or with other medications. While a diuretic is usually prescribed to increase urine production, in some patients with nephrogenic DI it can reduce urine production.

Prognosis

Uncomplicated diabetes insipidus is controllable with adequate intake of water and most patients can lead normal lives.

Resources

periodicals

Sanders, Lisa. “Addicted to Water.” The New York Times Magazine (October 14, 2007): 42.

organizations

American Diabetes Association, 1701 North Beauregard St, Alexandria, VA, 22311, (800) 342-2383, http://www.diabetes.org.

National Organization for Rare Disorders (NORD), 55 Kenosia Avenue, P.O. Box 1968, Danbury, CT, 06813-1968, (800) 999-6673, http://www.rarediseases.org.

Nephrogenic Diabetes Insipidus Foundation, Main Street, P.O. Box 1390, Eastsound, WA, 98245, (888) 376-6343, http://www.ndif.org.

The Diabetes Insipidus and Related Disorders Network, 535 Echo Court, Saline, MI, 48176-1270, (800) 457-6676, http://www.autopenhosting.org.

The Diabetes Insipidus Foundation, Inc., 3742 Woodland Drive, Columbus, GA, 31907, (706) 323–7576, http://www.diabetesinsipidus.org.

Rosalyn Carson-DeWitt MD

Lisa M. Piazza