Diabetes Insipidus

January 7, 2025

This page was reviewed under our medical and editorial policy by Ping H. Wang, M.D., professor and chair, Department of Diabetes, Endocrinology & Metabolism, City of Hope^® Cancer Center Duarte

Diabetes insipidus, also called arginine vasopressin disorder, is an uncommon condition that affects roughly 1 in 25,000 people worldwide, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

While it shares some symptoms with the more common diabetes mellitus, the two conditions are not related.

Diabetes insipidus occurs when the body produces too much urine. If not managed properly, it may lead to dehydration. Unlike diabetes mellitus, this condition does not affect blood sugar levels.

Understanding diabetes insipidus may help patients and their families recognize its symptoms and navigate appropriate treatment options.

What Is Diabetes Insipidus?

Diabetes insipidus is a condition that causes the body to produce unusually large amounts of clear or pale urine that lack the usual amounts of dissolved substances.

Most people produce about 1 to 3 quarts of urine a day, but someone with diabetes insipidus might make up to 20 quarts. This leads to frequent urination, called polyuria, and constant thirst, known as polydipsia. People with this condition may need to drink a lot of water each day to keep up with the fluid loss.

Diabetes insipidus may affect people of any age. It may be inherited or develop later in life. Some factors that may increase the risk for developing it include a family history of the disorder, brain surgery, a significant head injury or taking medications that affect the kidneys, such as certain psychiatric medications or diuretics. People with electrolyte issues like high calcium or low potassium levels are also at greater risk.

Diabetes Insipidus Versus Diabetes Mellitus

Diabetes insipidus and diabetes mellitus are different conditions, even though both may cause constant thirst, frequent urination and dehydration.

In type 1 diabetes and type 2 diabetes, high blood sugar levels lead to some of the excess glucose passing out of the body in the urine. The body struggles to control the extra sugar, causing the kidneys to work harder to remove it.

However, in diabetes insipidus, blood sugar levels are usually normal. The issue lies with the kidneys’ inability to properly concentrate urine. This leads to the production of large amounts of urine. Although the symptoms might seem similar, the causes and treatments are different.

Disease Types

There are four main subtypes of diabetes insipidus, each with its own causes and features. While all of the subtypes lead to excessive urination and thirst, the underlying reasons vary.

Nephrogenic Diabetes Insipidus

Nephrogenic diabetes insipidus (NDI) is a rare condition in which the kidneys do not respond normally to a hormone called antidiuretic hormone (ADH) or vasopressin.

Normally, ADH signals the kidneys to conserve water and make urine more concentrated. In people with NDI, the kidney tubules do not respond to ADH, so the kidneys release too much water into the urine. This leads to large amounts of diluted urine and excessive thirst.

NDI may be present at birth due to a genetic variant, more often affecting men. However, it might also be acquired later in life due to kidney issues, high levels of calcium or certain medications.

Recently, the name of this disorder was changed to arginine vasopressin resistance (AVP-R) to better reflect its causes and help reduce confusion with diabetes mellitus.

Central Diabetes Insipidus

Central diabetes insipidus occurs when the body doesn't produce enough antidiuretic hormone. ADH is made in the hypothalamus, a part of the brain, and stored in the pituitary gland. It helps the kidneys regulate how much water to keep in the body. When ADH levels are too low, the kidneys cannot retain enough water, leading to excessive urination and intense thirst.

People with central diabetes insipidus may need to drink large amounts of water to make up for the fluid loss. This condition may result from brain surgery, infection, tumors, injuries or inflammation. In rare cases, it may be inherited.

Patients may also hear this subtype called arginine vasopressin deficiency, or AVP-D.

Dipsogenic Diabetes Insipidus

Dipsogenic diabetes insipidus is caused by a problem in the hypothalamus, the part of the brain that controls thirst. People with this condition feel thirsty more often, leading them to drink large amounts of fluids. As a result, they urinate often because the body is trying to get rid of the excess water.

Dipsogenic diabetes insipidus may develop after damage to the hypothalamus from surgery, infections, tumors, head injuries or inflammation. In some cases, certain medications or mental health conditions (such as schizophrenia) might also contribute to this disorder.

Gestational Diabetes Insipidus

Gestational diabetes insipidus is a rare condition that may develop during pregnancy. It happens when the placenta produces too much of an enzyme that breaks down ADH. This causes the kidneys to release too much water, leading to excessive urination and thirst.

Women carrying multiple fetuses are at a higher risk because they have more placental tissue. Conditions affecting the liver during pregnancy, like preeclampsia and HELLP syndrome, may also increase the likelihood of developing this condition. Gestational diabetes insipidus is usually temporary and resolves after pregnancy.

Patients may also hear this called gestational AVP-D (gAVP-D).

Diabetes Insipidus Symptoms

The main symptoms of all forms of diabetes insipidus are:

• Excessive thirst
• Frequent urination
• Waking up at night to urinate (nocturia)

Adults with diabetes insipidus may produce much more than 3 liters of urine each day, while children might pass more than 2 liters per day. The urine is often very diluted in diabetes insipidus, even in the morning, when it is normally more concentrated. In some cases, people with diabetes insipidus may experience weakness, fatigue, muscle aches, low blood pressure and change of mental status. It can be life threatening if untreated. If the condition is related to a brain tumor, headaches and vision problems may also occur. In children, symptoms may be more vague and include dehydration, constipation, vomiting, irritability or slow growth.

Although rare, people with certain types of diabetes insipidus may also have lower bone mineral density in the spine and hips.

What Causes Diabetes Insipidus?

Diabetes insipidus occurs when the body is unable to properly regulate its water balance due to issues with a hormone called arginine vasopressin (AVP), also known as antidiuretic hormone (ADH) or just vasopressin. AVP is produced and stored in the brain, and it helps the kidneys manage how much water is reabsorbed or released as urine.

When the kidneys have trouble responding to AVP, the AVP hormone is not working correctly or is not released as it should be, the kidneys cannot retain enough water, leading to excessive urination. Or, sometimes, injuries or response to medications cause part of the brain to trigger extreme thirst and excessive urination.

In some cases, diabetes insipidus is caused by genetic mutations that affect the production or release of AVP. It may also develop from damage to the brain caused by head injuries, brain tumors, surgery, infections or bleeding. This damage interferes with the brain’s ability to produce or store AVP, or regulate thirst.

Sometimes, the cause is unknown. However, researchers believe some of these cases might involve the immune system attacking the body’s own tissues.

The Diagnosis Process

A workup for diabetes insipidus begins with a health care provider asking about the patient’s medical history and symptoms, focusing on thirst and urination patterns. Since many conditions cause similar symptoms, specific tests are usually needed to confirm the diagnosis and determine the subtype of diabetes insipidus.

Common tests include blood electrolytes, hormone levels and urine tests to check electrolytes, concentration and output measurements. Providers might use a desmopressin (DDAVP) challenge to see how the patient’s body responds to the synthetic version of the hormone vasopressin (ADH). Magnetic resonance imaging (MRI) of the head may also be done to check for issues with the pituitary gland or hypothalamus.

In some cases, the provider may refer the patient to a specialist in pituitary diseases, such as an endocrinologist, for further evaluation and to ensure an accurate diagnosis.

Diabetes Insipidus Treatment

Treatment varies depending on the subtype of diabetes insipidus and its underlying cause. The main treatment for diabetes insipidus is to treat the underlying causes and prevent patients from dehydration.

The most common treatment for central diabetes insipidus is desmopressin, a man-made hormone to replace the vasopressin the body is failing to make. It is administered as a pill, nasal spray or by injection.

Nephrogenic diabetes insipidus may improve after the underlying cause is addressed, such as adjusting medications or balancing calcium and potassium levels. Doctors may also prescribe thiazide diuretics or nonsteroidal anti-inflammatory drugs (NSAIDs) to help reduce urine output.

There is currently no appropriate treatment for dipsogenic diabetes insipidus, but there are supportive treatments to help manage the condition. Sucking on ice chips or sugar-free candies may help relieve thirst.

Additionally, a small dose of desmopressin before bed may reduce nighttime urination. Doctors often monitor blood sodium levels because they may drop too low with this condition and cause health issues.

For gestational diabetes insipidus, desmopressin is safe for both the mother and fetus. The condition usually resolves after childbirth, but it may return with future pregnancies.

Supportive Therapy

Supportive treatment for diabetes insipidus often involves making lifestyle changes to help manage symptoms. A low-sodium, low-protein diet may help the kidneys produce less urine, which may ease symptoms like excessive thirst and frequent urination. In some cases, particularly with nephrogenic diabetes insipidus, these dietary changes may be enough to keep symptoms under control.

Diabetes Insipidus Complications

If diabetes insipidus is left untreated, the main risk is dehydration. This occurs when the body loses too much fluid and essential minerals like sodium, potassium and magnesium. Without enough fluid and electrolytes, the body is unable to function properly.

Severe dehydration may cause serious complications, such as seizures, permanent brain damage or even death. It is important to seek medical attention immediately if symptoms like confusion, dizziness or extreme tiredness occur because these could signal dangerous levels of dehydration.

Life Expectancy for People With Diabetes Insipidus

The prognosis for diabetes insipidus largely depends on the underlying cause. When treated appropriately, the condition typically does not lead to severe complications or a shortened lifespan.

For people with central diabetes insipidus caused by issues like brain tumors or other disorders, the outlook often depends on managing the underlying problem.

Patients with nephrogenic diabetes insipidus generally have a good prognosis if the underlying cause is addressed. This may mean adjusting medications or treating related health conditions.

Pregnant women with gestational diabetes insipidus usually recover after childbirth, provided that they stay hydrated and follow medical advice.