Arginine Vasopressin Deficiency (AVP-D)

Arginine Vasopressin Deficiency (AVP-D), previously known as cranial or central diabetes insipidus (DI), is a rare condition in which the body does not produce or release enough of the hormone arginine vasopressin (AVP).

AVP is essential for maintaining the body's water balance. When there is not enough AVP, the kidneys are unable to retain sufficient water. This results in the production of large amounts of dilute urine and causes excessive thirst and drinking.

AVP-D can occur at any age, although it is more commonly diagnosed in adults.

The condition is rare. International estimates suggest that AVP-D/diabetes insipidus affects approximately 1 in 25,000 people, although there is currently no national registry in Ireland providing reliable prevalence data for AVP-D.

Important: AVP-D is not the same as diabetes mellitus (diabetes). Despite the similar name, the two conditions are completely different.

What is AVP?

Arginine vasopressin (AVP) is also known as antidiuretic hormone (ADH).

AVP plays an essential role in regulating the amount of water in your body.

AVP is produced by specialised nerve cells in an area of the brain called the hypothalamus. It is transported to the posterior (back) part of the pituitary gland, where it is stored and released into the bloodstream when the body needs it.

Once released, AVP travels through the bloodstream to the kidneys. It signals the kidneys to conserve water and reduce the amount of water lost in urine.

The body also uses thirst as an important part of its water-balance system. When the body detects that it is becoming dehydrated, thirst encourages you to drink more while AVP helps the kidneys retain water.

These two mechanisms work together to keep the body's water and sodium levels within a safe range. (Cambridge University Hospitals⁠)

How does AVP-D affect the body?

A useful way of understanding water balance is to think of your body like a bath with a tap and a plug.

• Drinking fluids is like turning on the tap and adding water.
• The kidneys are like the plug, controlling how much water leaves the body.
• AVP helps keep the plug in by telling the kidneys to retain water.
• Thirst encourages you to turn the tap on when your body needs more water.

Normally, when the body has too little water, thirst increases and more AVP is released. This makes you drink more while your kidneys conserve water.

When the body has enough water, thirst decreases and less AVP is released, allowing the kidneys to remove more water in urine.

In AVP-D, there is insufficient AVP activity. The kidneys therefore continue to lose large amounts of water, producing large volumes of very dilute urine.

This loss of water causes increased thirst, encouraging the person to drink enough to replace the fluid being lost.
 

Symptoms of AVP-D

The main symptoms of AVP-D are:

• Excessive thirst (polydipsia)
• Passing large amounts of urine (polyuria)
• Frequent urination, including needing to get up repeatedly during the night
• Passing urine that is very pale or almost clear
• Drinking unusually large amounts of fluid
• A strong preference for very cold drinks
• Dry mouth, lips, skin or eyes
• Headaches
• Tiredness or exhaustion
• Shivering
• Nausea
• Weight loss
• Symptoms of dehydration

Some people may produce 4–10 litres of urine or more in 24 hours, although the amount varies between individuals.

The excessive thirst associated with AVP-D can be extremely difficult to ignore. Some people describe it as a persistent, intense thirst that does not disappear even after drinking substantial amounts of fluid.

Night-time symptoms

AVP-D can have a significant impact on sleep because of the need to drink and urinate frequently during the night.

Some people may wake several times each night to drink and pass urine, which can contribute to ongoing fatigue and exhaustion. (Pituitary Foundation⁠)

Dehydration

If the amount of water being lost is greater than the amount being replaced, dehydration can develop.

Symptoms may include:

• Very dry mouth
• Cracked lips
• Dry skin
• Dry or irritated eyes
• Headache
• Dizziness
• Weakness or exhaustion
• Nausea
• Shivering
• Increasing thirst

It is important not to deliberately restrict your fluid intake to reduce the amount of urine you pass. In untreated or inadequately treated AVP-D, restricting fluids can lead to serious dehydration and disturbances in blood sodium levels.

AVP-D and an absent thirst mechanism

Most people with AVP-D experience increased thirst, which helps protect the body from dehydration.

A small number of people have reduced or absent thirst, known as hypodipsia or adipsia.

When AVP-D occurs together with an impaired thirst mechanism, it can be particularly challenging because the normal warning signal to drink may be absent.

People affected by this combination require carefully planned fluid management and close medical supervision.

What causes AVP-D?

AVP-D occurs when the system responsible for producing, transporting, storing or releasing AVP is damaged or does not function properly.

Possible causes include conditions affecting the hypothalamus or pituitary gland, including:

• Pituitary surgery
• Brain surgery
• Head injury
• Tumours affecting the pituitary or hypothalamus
• Craniopharyngioma
• Other disorders affecting the hypothalamus or pituitary gland
• Certain inflammatory or autoimmune conditions
• Some infections
• Rare genetic conditions

In some people, no clear cause can be identified. This is sometimes referred to as idiopathic AVP-D. (nhs.uk⁠)

AVP-D can also occur following surgery or treatment involving the pituitary or surrounding structures.

AVP Resistance (AVP-R)

Arginine Vasopressin Resistance (AVP-R) was previously known as nephrogenic diabetes insipidus.

AVP-R is different from AVP-D and is not usually caused by a problem with the pituitary gland.

In AVP-R, the body produces AVP but the kidneys do not respond properly to its signal. As a result, the kidneys continue to lose excessive amounts of water.

The main symptoms are similar to AVP-D:

• Excessive thirst
• Excessive drinking
• Passing large amounts of dilute urine
• Frequent urination, including at night

AVP-R can be inherited or acquired during life.

Acquired AVP-R can be associated with certain medications, particularly lithium, as well as some kidney conditions and abnormalities in blood potassium or calcium levels. (nhs.uk⁠)

The distinction between AVP-D and AVP-R is important because their causes and treatments can be different.

How is AVP-D diagnosed?

AVP-D can be difficult to diagnose because excessive thirst and frequent urination can occur for many different reasons.

Your doctor may initially investigate more common causes of excessive urination and thirst, including diabetes mellitus.

If AVP-D is suspected, you may be referred to an endocrinologist for further investigation.

Tests may include:

24-hour urine collection

You may be asked to collect all the urine you produce over a 24-hour period.

This can establish how much urine you are producing and help confirm whether you have significant polyuria.

Blood tests

Blood tests may be used to assess:

• Sodium levels
• Blood osmolality
• Glucose
• Potassium
• Calcium
• Kidney function

Blood and urine results are often considered together when investigating AVP-D. (nhs.uk⁠)

Urine tests

Urine may be tested to determine how concentrated or dilute it is.

In AVP-D, urine is typically very dilute because the kidneys are unable to retain water effectively.

Water deprivation test

A water deprivation test may be used when the diagnosis is uncertain.

During this test, you are carefully monitored while fluids are withheld for a period of time under medical supervision. Your weight, urine output and blood and urine measurements are monitored.

Normally, when fluid intake stops, the body increases AVP activity and the kidneys concentrate the urine.

In AVP-D, the urine remains excessively dilute because there is insufficient AVP activity.

A dose of desmopressin, which acts like AVP, may then be given. If urine production falls and the urine becomes more concentrated, this can support a diagnosis of AVP-D. If the kidneys do not respond appropriately, AVP-R may be considered.

A water deprivation test should only be carried out under appropriate medical supervision because dehydration and changes in blood sodium can occur. (nhs.uk⁠)

MRI scan

If AVP-D is suspected to be related to the pituitary gland or hypothalamus, your endocrinologist may arrange an MRI scan of the brain and pituitary region.

The scan may help identify an underlying cause such as a pituitary or hypothalamic tumour or changes associated with previous surgery or injury. (nhs.uk⁠)

How is AVP-D treated?

The main treatment for AVP-D is desmopressin, a medication that acts in a similar way to natural AVP.

Desmopressin helps the kidneys retain water, reducing excessive urine production and helping control thirst.

It is also known by brand names including DDAVP®.

Treatment is individually tailored by your endocrinologist. The amount and frequency of desmopressin required can vary considerably between people.

Desmopressin preparations

Desmopressin may be available in several forms, including:

• Oral tablets
• Oral lyophilisates or wafers that dissolve in the mouth
• Nasal spray
• Nasal drops
• Injection

The most appropriate preparation depends on your individual circumstances, treatment requirements and preferences.

Injections are generally used in specific circumstances, including when oral or nasal treatment cannot be used, and may be administered in hospital or other clinical settings. (Pituitary Foundation⁠)

Your endocrinologist will advise you on the correct dose and timing.

Do not change your desmopressin dose or schedule without medical advice.

What is a "breakthrough"?

People living with AVP-D often use the term "breakthrough" to describe the return of symptoms as the effect of a dose of desmopressin begins to wear off.

You may notice:

• Increasing urine production
• Urine becoming paler
• Increasing thirst
• Needing to urinate more frequently

The timing of breakthrough varies from person to person and may change depending on illness, fluid intake, medication and other factors.

Some people deliberately allow a period of breakthrough as part of their individual treatment plan. This can allow excess water to be passed before the next dose.

However, the timing and management of breakthrough should be discussed with your endocrinologist, particularly if your usual pattern changes.

Desmopressin and low sodium levels

Desmopressin is generally very effective in controlling AVP-D, but it needs to be used carefully.

Because desmopressin causes the kidneys to retain water, taking too much medication or drinking excessive amounts of fluid while its effect is active can cause water to accumulate in the body.

This can result in hyponatraemia, meaning that the sodium concentration in the blood becomes too low.

Symptoms of hyponatraemia can include:

• Headache
• Nausea or vomiting
• Feeling unusually tired
• Confusion
• Drowsiness
• Muscle cramps or weakness

Severe hyponatraemia can be a medical emergency.

Your endocrinology team will advise you about your individual fluid intake, desmopressin dose and monitoring requirements.

Illness, vomiting and diarrhoea

Illness can make managing AVP-D more difficult.

Vomiting or diarrhoea can cause additional fluid loss and may affect how well oral medication is absorbed.

If you are unable to keep fluids or your usual medication down, you should seek urgent medical advice.

People who have AVP-D alongside other pituitary hormone deficiencies, particularly adrenal insufficiency, may have additional emergency medication and sick-day requirements.

If you have been prescribed emergency medication or given specific sick-day instructions by your endocrinology team, make sure you understand when and how to use them.

Changing between desmopressin products

Different formulations and brands of desmopressin may be available.

Although generic versions contain the same active medication, some people may notice a change in how long their medication appears to work or when breakthrough symptoms occur after a change in product or formulation.

If your desmopressin brand, formulation or prescription is changed and you notice a significant change in:

• Thirst
• Urine production
• Timing of breakthrough
• Fluid balance
• General wellbeing

contact your GP, pharmacist or endocrinology team for advice.

Do not make changes to your treatment yourself.

Living with AVP-D

With appropriate treatment and monitoring, many people with AVP-D are able to live full and active lives.

However, AVP-D requires ongoing awareness of fluid balance, medication and access to appropriate medical care.

It can be helpful to:

• Carry your medication with you
• Ensure you have enough medication when travelling
• Keep a record of your medication and dosing schedule
• Make sure family members or close friends understand your condition
• Tell healthcare professionals that you have AVP-D
• Wear or carry appropriate medical identification
• Discuss travel arrangements and emergency planning with your healthcare team

If you have AVP-D because of a pituitary condition or pituitary surgery, you may also have other hormone deficiencies requiring lifelong hormone replacement.

When should I seek medical help?

Contact your healthcare team if you experience a significant or unexplained change in your usual pattern of:

• Thirst
• Urine production
• Desmopressin response
• Breakthrough timing
• Fluid intake
• General wellbeing

Seek urgent medical attention if you are unable to drink, cannot keep your medication down, become severely dehydrated, or develop significant confusion, drowsiness, weakness or other concerning symptoms.

Remember

AVP-D is a lifelong condition for many people, but it can usually be managed effectively with appropriate treatment and monitoring.

If you have been diagnosed with AVP-D, your endocrinologist should provide an individual treatment plan explaining your desmopressin dose, fluid management, monitoring and what to do during illness or emergencies.

Never deliberately restrict fluids to try to reduce urination unless this has specifically been advised and is being medically supervised.

Medical information disclaimer

The information on this page is provided for general educational purposes and is not intended to replace advice from a qualified healthcare professional.

If you have symptoms that concern you, or if you are worried about your diagnosis or treatment, speak with your GP, endocrinologist, pharmacist or other appropriate healthcare professional.

Treatment should always be individualised to your circumstances.