diabetes insipidus

What is diabetes insipidus

Diabetes insipidus is a rare disorder that occurs when a person’s kidneys pass an abnormally large volume of urine that is insipid—dilute and odorless. In most people, the kidneys pass about 1 to 2 quarts (0.946 to 1.89 liter) of urine a day. In people with diabetes insipidus, the kidneys can pass 3 to 21 quarts (2.83 to 20 liters) of urine a day. As a result, a person with diabetes insipidus may feel the need to drink large amounts of liquids. You become extremely thirsty, so you drink. Then you urinate. This cycle can keep you from sleeping or even make you wet the bed. Your body produces lots of urine that is almost all water.

The two main symptoms of diabetes insipidus are:

  • Extreme thirst (polydipsia). It’s likely that you’ll feel thirsty all the time and have a ‘dry’ feeling that’s always present, no matter how much water you drink.
  • Passing large amounts of urine, even at night (polyuria). You may pass pale, watery urine every 15-20 minutes. The amount of urine passed can range from 3 liters in mild cases to up to 20 liters in severe cases.

You may also feel generally unwell and ‘run down’ much of the time for no apparent reason.

Usually, diabetes insipidus is caused by a problem with your pituitary gland or your kidneys. Treatment depends on the cause of the problem. Medicines can often help.

Diabetes insipidus vs Diabetes mellitus

Diabetes insipidus and diabetes mellitus—which includes both type 1 and type 2 diabetes—are unrelated, although both conditions cause frequent urination and constant thirst. Diabetes mellitus which involves insulin problems and high blood sugar or high blood glucose, resulting from the body’s inability to use blood glucose for energy. People with diabetes insipidus have normal blood glucose levels; however, their kidneys cannot balance fluid in the body.

The kidneys and what do they do

You have two kidneys that are reddish, kidney bean–shaped organs located just above the waist between the peritoneum and the posterior wall of the abdomen. The kidneys are located between the levels of the last thoracic vertebrae T12 and third lumbar (L3) vertebrae, a position where they are partially protected by ribs 11 and 12. A typical adult kidney is 10–12 cm (4–5 in.) long, 5–7 cm (2–3 in.) wide, and 3 cm (1 in.) thick—about the size of a bar of bath soap—and weighs about 135–150 g (4.5–5 oz).

Every day, the kidneys normally filter about 120 to 150 quarts (113.5 to 141.9 liters) of blood to produce about 1 to 2 quarts (0.946 to 1.89 liter) of urine, composed of wastes and extra fluid. The urine flows from the kidneys to the bladder through tubes called ureters. The bladder stores urine. When the bladder empties, urine flows out of the body through a tube called the urethra, located at the bottom of the bladder.

Figure 1. Kidney location

kidney location

Figure 2. The hypothalamus and pituitary gland location

pituitary gland

Figure 3. The hypothalamus and pituitary gland (anterior and posterior) endocrine pathways and target organs

Hypothalamus hormones

How is fluid regulated in the body?

A person’s body regulates fluid by balancing liquid intake and removing extra fluid. Thirst usually controls a person’s rate of liquid intake, while urination removes most fluid, although people also lose fluid through sweating, breathing, or diarrhea. The hormone vasopressin, also called antidiuretic hormone (ADH), controls the fluid removal rate through urination. The hypothalamus, a small gland located at the base of the brain, produces vasopressin or antidiuretic hormone (ADH). The nearby pituitary gland stores the vasopressin and releases it into the bloodstream when the body has a low fluid level. Vasopressin signals the kidneys to absorb less fluid from the bloodstream, resulting in less urine. When the body has extra fluid, the pituitary gland releases smaller amounts of vasopressin, and sometimes none, so the kidneys remove more fluid from the bloodstream and produce more urine.

Types of diabetes insipidus

The types of diabetes insipidus include:

  • central
  • nephrogenic
  • dipsogenic
  • gestational

Each type of diabetes insipidus has a different cause.

Central Diabetes Insipidus

Central diabetes insipidus happens when damage to a person’s hypothalamus or pituitary gland causes disruptions in the normal production, storage, and release of vasopressin or antidiuretic hormone (ADH). The disruption of vasopressin or antidiuretic hormone (ADH) causes the kidneys to remove too much fluid from the body, leading to an increase in urination.

Damage to the hypothalamus or pituitary gland can result from the following:

  • surgery
  • infection
  • inflammation
  • a tumor
  • head injury

Central diabetes insipidus can also result from an inherited defect in the gene that produces vasopressin/antidiuretic hormone (ADH), although this cause is rare. In some cases, the cause is unknown.

Nephrogenic Diabetes Insipidus

Nephrogenic diabetes insipidus occurs when the kidneys do not respond normally to vasopressin/antidiuretic hormone (ADH) and continue to remove too much fluid from a person’s bloodstream. Nephrogenic diabetes insipidus can result from inherited gene changes, or mutations, that prevent the kidneys from responding to vasopressin.

Other causes of nephrogenic diabetes insipidus include:

  • chronic kidney disease
  • certain medications, particularly lithium
  • low potassium levels in the blood
  • high calcium levels in the blood
  • blockage of the urinary tract

The causes of nephrogenic diabetes insipidus can also be unknown.

Dipsogenic Diabetes Insipidus

A defect in the thirst mechanism, located in a person’s hypothalamus, causes dipsogenic diabetes insipidus. This defect results in an abnormal increase in thirst and liquid intake that suppresses vasopressin/antidiuretic hormone (ADH) secretion and increases urine output. The same events and conditions that damage the hypothalamus or pituitary—surgery, infection, inflammation, a tumor, head injury—can also damage the thirst mechanism. Certain medications or mental health problems may predispose a person to dipsogenic diabetes insipidus.

Gestational Diabetes Insipidus

Gestational diabetes insipidus occurs only during pregnancy. In some cases, an enzyme made by the placenta—a temporary organ joining mother and baby—breaks down the mother’s vasopressin/antidiuretic hormone (ADH). In other cases, pregnant women produce more prostaglandin, a hormone-like chemical that reduces kidney sensitivity to vasopressin. Most pregnant women who develop gestational diabetes insipidus have a mild case that does not cause noticeable symptoms. Gestational diabetes insipidus usually goes away after the mother delivers the baby; however, it may return if the mother becomes pregnant again.

Diabetes insipidus complications

The two main complications of diabetes insipidus are dehydration and an electrolyte imbalance. Complications are more likely if the condition goes undiagnosed or is poorly controlled.


If you have diabetes insipidus, your body will find it difficult to retain enough water, even if you drink fluid constantly. This can lead to dehydration (a severe lack of water in the body).

If you or someone you know has diabetes insipidus, it’s important to look out for the signs and symptoms of dehydration.

Signs of dehydration include:

  • thirst
  • dry skin
  • fatigue
  • sluggishness
  • dizziness
  • confusion
  • nausea
  • dizziness or light-headedness
  • headache
  • dry mouth and lips
  • sunken features (particularly the eyes)
  • confusion and irritability

Severe dehydration can lead to seizures, permanent brain damage, and even death.

Dehydration can be treated by rebalancing the level of water in your body.

If you’re severely dehydrated, you may need intravenous fluid replacement in hospital. This is where fluids are given directly through a drip into your vein.

Electrolyte imbalance

Diabetes insipidus can also cause an electrolyte imbalance. Electrolytes are minerals in your blood that have a tiny electric charge, such as sodium, calcium, potassium, chlorine, magnesium and bicarbonate.

If the body loses too much water, the concentration of these electrolytes can go up simply because the amount of water they’re contained in has gone down.

This dehydration disrupts other functions of the body, such as the way muscles work. It can also lead to:

  • headache
  • fatigue (feeling tired all the time)
  • irritability
  • muscle pain.

Diabetes insipidus causes

Diabetes insipidus is caused by problems with a chemical called vasopressin, which is also known as antidiuretic hormone (ADH).

Vasopressin is produced by the hypothalamus and stored in the pituitary gland until needed. The hypothalamus is an area of the brain that controls mood and appetite. The pituitary gland is located below your brain, behind the bridge of your nose.

Vasopressin/antidiuretic hormone (ADH) regulates the level of water in your body by controlling the amount of urine your kidneys produce. When the level of water in your body decreases, your pituitary gland releases vasopressin to conserve water and stop the production of urine.

In diabetes insipidus, vasopressin/antidiuretic hormone (ADH) fails to properly regulate your body’s level of water, and allows too much urine to be produced and passed from your body.

There are two main types of diabetes insipidus:

  • central diabetes insipidus – where the body doesn’t produce enough vasopressin, so excessive amounts of water are lost in large amounts of urine
  • nephrogenic diabetes insipidus – where vasopressin is produced at the right levels but, for a variety of reasons, the kidneys don’t respond to it in the normal way.

Possible underlying causes for both types of diabetes insipidus are described below.

Central diabetes insipidus

The three most common causes of central diabetes insipidus are:

  • a brain tumor that damages the hypothalamus or pituitary gland
  • a severe head injury that damages the hypothalamus or pituitary gland
  • complications that occur during brain or pituitary surgery

No cause can be found for about a third of all cases of central diabetes insipidus. These cases, known as idiopathic, appear to be related to the immune system attacking the normal, healthy cells producing vasopressin. It’s unclear what causes the immune system to do this.

Less common causes of central diabetic insipidus include:

  • cancers that spread from another part of the body to the brain
  • Wolfram syndrome, which is a rare genetic disorder that also causes vision loss
  • brain damage caused by a sudden loss of oxygen, which can occur during a stroke or drowning
  • infections, such as meningitis and encephalitis, that can damage the brain

Nephrogenic diabetes insipidus

Your kidneys contain nephrons, which are tiny intricate structures that filter waste products from the blood and help produce urine. They also control how much water is reabsorbed into your body and how much is passed in the urine.

In a healthy person, vasopressin acts as a signal to the nephrons to reabsorb water into the body. In nephrogenic diabetes insipidus, the nephrons in the kidney aren’t able to respond to this signal, leading to excessive water loss in large amounts of urine. Your thirst increases to try to balance this loss from the body.

Nephrogenic diabetes insipidus can be congenital (present at birth) or acquired (where it develops later in life as a result of an external factor). These are described in more detail below.

Congenital nephrogenic diabetes insipidus

Two genetic mutations (abnormal changes in genes that leads to them not working properly) have been identified that cause congenital nephrogenic diabetes insipidus.

The first, known as the vasopressinR2 gene mutation, is responsible for 90% of all cases of congenital diabetes insipidus. However, it’s still rare, occurring in an estimated 1 in 250,000 births.

The vasopressinR2 gene mutation can only be passed down by mothers (who may appear to not be affected) to their sons (who are affected).

The remaining 10% of cases of congenital nephrogenic diabetes insipidus are caused by the AQP2 gene mutation, which can affect both males and females.

Acquired nephrogenic diabetes insipidus

Lithium is the most common cause of acquired nephrogenic diabetes insipidus. It’s a medication that’s often used to treat bipolar disorder. Long-term lithium use can damage the cells of the kidneys so they no longer respond to vasopressin.

Just over half of all people on long-term lithium therapy develop some degree of nephrogenic diabetes insipidus. Stopping lithium treatment often restores normal kidney function, although in many cases the damage to the kidneys is permanent.

Due to these risks, it’s recommended that you have kidney function tests every three months if you’re taking lithium.

Other causes of acquired nephrogenic diabetes insipidus include:

  • hypercalcaemia – a condition where there’s too much calcium in the blood (high calcium levels can damage the kidneys)
  • hypokalemia – a condition where there isn’t enough potassium in the blood (all the cells in the body, including kidney cells, require potassium to function properly)
  • pyelonephritis (kidney infection) – where the kidneys are damaged by an infection
  • ureteral obstruction – where one or both tubes (ureters) that connect the kidneys to the bladder become blocked by an object, such as a kidney stone, which damages the kidneys

Diabetes insipidus signs and symptoms

The most common signs and symptoms of diabetes insipidus are:

  • Extreme thirst
  • Excretion of an excessive amount of diluted urine

If you have diabetes insipidus, you may pass pale, watery urine every 15-20 minutes. The amount of urine passed can range from 3 liters in mild cases to up to 20 liters in severe cases.

Other signs may include needing to get up at night to urinate (nocturia) and bed-wetting.

It’s also likely that you’ll feel thirsty all the time and have a ‘dry’ feeling that’s always present, no matter how much water you drink.

If you need to pass urine regularly and always feel thirsty, your sleeping patterns and daily activities may be disrupted. This can cause tiredness, irritability and difficulty concentrating, which can affect your daily life further.

You may also feel generally unwell and ‘run down’ much of the time for no apparent reason.

Symptoms in children

Excessive thirst can be difficult to recognize in children who are too young to speak.

Signs and symptoms that could suggest diabetes insipidus include:

  • excessive crying
  • irritability
  • slower than expected growth
  • hyperthermia (high body temperature)
  • unexplained weight loss

In older children, symptoms of diabetes insipidus include:

  • wetting the bed (enuresis) – although most children who wet the bed don’t have diabetes insipidus
  • loss of appetite
  • feeling tired all the time (fatigue)

Diabetes insipidus diagnosis

As the symptoms of diabetes insipidus are similar to those of other conditions, including type 1 diabetes and type 2 diabetes, tests will be needed to confirm which condition you have.

If diabetes insipidus is diagnosed, the tests will also be able to identify the type you have – central or nephrogenic diabetes insipidus.

A health care provider can diagnose a person with diabetes insipidus based on the following:

  • medical and family history
  • physical exam
  • urinalysis
  • blood tests
  • fluid deprivation test
  • magnetic resonance imaging (MRI)

Medical and Family History

Taking a medical and family history can help a health care provider diagnose diabetes insipidus. A health care provider will ask the patient to review his or her symptoms and ask whether the patient’s family has a history of diabetes insipidus or its symptoms.

Physical Exam

A physical exam can help diagnose diabetes insipidus. During a physical exam, a health care provider usually examines the patient’s skin and appearance, checking for signs of dehydration.


Urinalysis tests a urine sample. A patient collects the urine sample in a special container at home, in a health care provider’s office, or at a commercial facility. A health care provider tests the sample in the same location or sends it to a lab for analysis. The test can show whether the urine is dilute or concentrated. The test can also show the presence of glucose, which can distinguish between diabetes insipidus and diabetes mellitus. The health care provider may also have the patient collect urine in a special container over a 24-hour period to measure the total amount of urine produced by the kidneys.

Blood Tests

A blood test involves drawing a patient’s blood at a health care provider’s office or a commercial facility and sending the sample to a lab for analysis. The blood test measures sodium levels, the levels of antidiuretic hormone (ADH) in your blood, which can help diagnose diabetes insipidus and in some cases determine the type.

Your blood and urine may also be tested for substances such as glucose (blood sugar), calcium and potassium. If you have diabetes insipidus, your urine will be very dilute, with low levels of other substances. A large amount of sugar in your urine may be a sign of type 1 or type 2 diabetes rather than diabetes insipidus.

Fluid Deprivation Test

A fluid deprivation test measures changes in a patient’s body weight and urine concentration after restricting liquid intake. If you have diabetes insipidus, you’ll continue to pass large amounts of dilute urine, when normally you’d only pass a small amount of concentrated urine.

A health care provider can perform two types of fluid deprivation tests:

  • A short form of the deprivation test. A health care provider instructs the patient to stop drinking all liquids for a specific period of time, usually during dinner. The next morning, the patient will collect a urine sample at home. The patient then returns the urine sample to his or her health care provider or takes it to a lab where a technician measures the concentration of the urine sample.
  • A formal fluid deprivation test. A health care provider performs this test in a hospital to continuously monitor the patient for signs of dehydration. Patients do not need anesthesia. A health care provider weighs the patient and analyzes a urine sample. The health care provider repeats the tests and measures the patient’s blood pressure every 1 to 2 hours until one of the following happens:
    • The patient’s blood pressure drops too low or the patient has a rapid heartbeat when standing.
    • The patient loses 5 percent or more of his or her initial body weight.
    • Urine concentration increases only slightly in two to three consecutive measurements.

    At the end of the test, a health care provider will compare the patient’s blood sodium, vasopressin levels, and urine concentration to determine whether the patient has diabetes insipidus. Sometimes, the health care provider may administer medications during the test to see if they increase a patient’s urine concentration. In other cases, the health care provider may give the patient a concentrated sodium solution intravenously at the end of the test to increase the patient’s blood sodium level and determine if he or she has diabetes insipidus.

Vasopressin test

After the water deprivation test, you may be given a small dose of vasopressin, usually as an injection. This will show how your body reacts to the hormone, which helps to identify the type of diabetes insipidus you have.

If the dose of vasopressin stops you producing urine, it’s likely your condition is due to a shortage of vasopressin. If this is the case, you may be diagnosed with central or cranial diabetes insipidus.

If you continue to produce urine despite the dose of vasopressin, this suggests there’s already enough vasopressin in your body, but your kidneys aren’t responding to it. In this case, you may be diagnosed with nephrogenic diabetes insipidus.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a test that takes pictures of the body’s internal organs and soft tissues without using x-rays. A specially trained technician performs the procedure in an outpatient center or a hospital, and a radiologist—a doctor who specializes in medical imaging—interprets the images. A patient does not need anesthesia, although people with a fear of confined spaces may receive light sedation. An MRI may include an injection of a special dye, called contrast medium. With most MRI machines, the person lies on a table that slides into a tunnel-shaped device that may be open ended or closed at one end. Some MRI machines allow the patient to lie in a more open space. MRIs cannot diagnose diabetes insipidus. Instead, an MRI can show if the patient has problems with his or her hypothalamus or pituitary gland or help the health care provider determine if diabetes insipidus is the possible cause of the patient’s symptoms.

Genetic screening

If your doctor suspects an inherited form of diabetes insipidus, he or she will look at your family history of polyuria and may suggest genetic screening.

Diabetes insipidus treatment

The primary treatment for diabetes insipidus involves drinking enough liquid to prevent dehydration. A health care provider may refer a person with diabetes insipidus to a nephrologist—a doctor who specializes in treating kidney problems—or to an endocrinologist—a doctor who specializes in treating disorders of the hormone-producing glands. Treatment for frequent urination or constant thirst depends on the patient’s type of diabetes insipidus:

Central diabetes insipidus

Mild central diabetes insipidus may not require any medical treatment.

Central diabetes insipidus is considered mild if you produce approximately 3-4 liters of urine over 24 hours.

If this is the case, you may be able to ease your symptoms by increasing the amount of water you drink, to avoid dehydration. Your doctor or endocrinologist (specialist in hormone conditions) may advise you to drink a certain amount of water every day, usually at least 2.5 liters.

However, if you have more severe central diabetes insipidus, drinking water may not be enough to control your symptoms. As your condition is due to a shortage of vasopressin, your doctor or endocrinologist may prescribe a treatment that takes the place of vasopressin, known as desmopressin.


A synthetic, or man-made, hormone called desmopressin treats central diabetes insipidus. Desmopressin is more powerful and more resistant to being broken down than the vasopressin naturally produced by your body. It works just like natural vasopressin, stopping your kidneys producing urine when the level of water in your body is low. The medication comes as an injection, a nasal spray, or a pill. The medication works by replacing the vasopressin that a patient’s body normally produces. This treatment helps a patient manage symptoms of central diabetes insipidus; however, it does not cure the disease.

If you’re prescribed desmopressin as a nasal spray, you’ll need to spray it inside your nose once or twice a day, where it’s quickly absorbed into your bloodstream.

If you’re prescribed desmopressin tablets, you may need to take them more than twice a day. This is because desmopressin is absorbed into your blood less effectively through your stomach than through your nasal passages, so you need to take more to have the same effect.

Your doctor or endocrinologist may suggest switching your treatment to tablets if you develop a cold that prevents you from using the nasal spray.

Desmopressin is very safe to use and has few side effects.

However, possible side effects can include:

  • headache
  • stomach pain
  • feeling sick
  • blocked or runny nose
  • nosebleeds

If you take too much desmopressin or drink too much fluid while taking it, it can cause your body to retain too much water.

This can result in:

  • headaches
  • dizziness
  • feeling bloated
  • hyponatremia – a low level of sodium (salt) in your blood

Symptoms of hyponatremia include:

  • a severe or prolonged headache
  • confusion
  • nausea and vomiting

If you think you may have hyponatremia, stop taking desmopressin immediately and call your doctor for advice.

Nephrogenic diabetes insipidus

In some cases, nephrogenic diabetes insipidus goes away after treatment of the cause. For example, switching medications or taking steps to balance the amount of calcium or potassium in the patient’s body may resolve the problem.

As nephrogenic diabetes insipidus is caused by your kidneys not responding to vasopressin, rather than a shortage of vasopressin, it usually can’t be treated with desmopressin. However, it’s still important to drink plenty of water to avoid dehydration.

If your condition is mild, your doctor or endocrinologist may suggest reducing the amount of salt and protein in your diet, which will help your kidneys produce less urine. This may mean eating less salt and protein-rich food, such as processed foods, meat, eggs and nuts. Don’t alter your diet without first seeking medical advice. Your doctor or endocrinologist will be able to advise you about which foods to cut down on.

If you have more severe nephrogenic diabetes insipidus, you may be prescribed a combination of thiazide diuretics and an NSAID to help reduce the amount of urine your kidneys produce.

Medications for nephrogenic diabetes insipidus include diuretics, either alone or combined with aspirin or ibuprofen. Health care providers commonly prescribe diuretics to help patients’ kidneys remove fluid from the body. Paradoxically, in people with nephrogenic diabetes insipidus, a class of diuretics called thiazides reduces urine production and helps patients’ kidneys concentrate urine. Aspirin or ibuprofen also helps reduce urine volume.

Thiazide diuretics

Thiazide diuretics can reduce the rate the kidney filters blood, which reduces the amount of urine passed from the body over time.

Side effects are uncommon but include:

  • dizziness when standing
  • indigestion
  • very sensitive skin
  • erectile dysfunction (impotence) in men

This last side effect is usually temporary and should resolve itself if you stop taking the medication.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, help reduce urine volume further when they’re used in combination with thiazide diuretics.

However, long-term use of NSAIDs increases your risk of developing a stomach ulcer. To counter this increased risk, an additional medication called a proton pump inhibitor (PPI) may be prescribed. PPIs help protect your stomach lining against the harmful effects of NSAIDs, reducing the risk of ulcers forming.

Dipsogenic diabetes insipidus

Researchers have not yet found an effective treatment for dipsogenic diabetes insipidus. People can try sucking on ice chips or sour candies to moisten their mouths and increase saliva flow, which may reduce the desire to drink. For a person who wakes multiple times at night to urinate because of dipsogenic diabetes insipidus, taking a small dose of desmopressin at bedtime may help. Initially, the health care provider will monitor the patient’s blood sodium levels to prevent hyponatremia, or low sodium levels in the blood.

Gestational diabetes insipidus

A health care provider can prescribe desmopressin for women with gestational diabetes insipidus. An expecting mother’s placenta does not destroy desmopressin as it does vasopressin. Most women will not need treatment after delivery.

Most people with diabetes insipidus can prevent serious problems and live a normal life if they follow the health care provider’s recommendations and keep their symptoms under control.

Lifestyle and home remedies

If you have diabetes insipidus:

  • Prevent dehydration. As long as you take your medication and have access to water when the medication’s effects wear off, you’ll prevent serious problems. Plan ahead by carrying water with you wherever you go, and keep a supply of medication in your travel bag, at work or at school.
  • Wear a medical alert bracelet or carry a medical alert card in your wallet. If you have a medical emergency, a health care professional will recognize immediately your need for special treatment.

Eating, Diet, and Nutrition

Researchers have not found that eating, diet, and nutrition play a role in causing or preventing diabetes insipidus.