Alternative names for diabetes insipidus
AVP-Deficiency and AVP-Resistance; Cranial Diabetes Insipidus; Nephrogenic Diabetes Insipidus; Diabetes Insipidus; Vasopressin Related Polyuria; AVP-Related Polyuria
What is Vasopressin Related Polyuria?
Vasopressin Related Polyuria is a condition caused by impaired production of, or a response to, vasopressin (AVP) which is also known as ADH (Antidiuretic hormone). We will use the terms AVP and AVP-Related Polyuria throughout this article, rather than ADH and Diabetes Inspidus.
AVP is a hormone produced and stored in the hypothalamus. It is then transported and secreted into the posterior pituitary gland from which is enters the bloodstream when stimulated by ‘osmoreceptors’ that detect when the body is dehydrated. AVP stimulates the kidneys to produce more concentrated urine to reduce water loss and retain water in the body. AVP therefore plays an important role in controlling the fluid balance in the body.
What is the difference between AVP-Deficiency and AVP-Resistance?
There are two main types of AVP-Related Polyuria. AVP-Deficiency (previously known as Cranial Diabetes Insipidus) and AVP-Resistance (also known as AVP-R or previously known as Nephrogenic Diabetes Insipidus).
AVP-Deficiency (AVP-D) is a condition in which the hypothalamus does not produce enough AVP and is the most common type, usually due to pituitary disease. AVP-Deficiency can occur in pregnancy (called gestational AVP-D), and may also be inherited.
AVP-Resistance (AVP-R) is a condition in which the kidneys fail to respond to AVP. This may be due to kidney disease or abnormal electrolytes such as low potassium or high calcium levels in the blood. It can also occasionally be inherited.
Both AVP-Deficiency and AVP-Resistance mean that the kidneys are unable to retain water, leading to the passing of too much dilute urine (pale urine). In severe cases, up to 20 litres of urine are passed in one day. This can occur even when the body is dehydrated and should be trying to save fluid by producing concentrated urine (dark urine).
Patients with psychological disease may have a behavioural desire to drink an abnormally high amount of water (called Primary Polydipsia). It is important to distinguish Primary Polydipsia from AVP-Related Polyuria as getting the wrong diagnosis may lead to incorrect treatment i.e. the administration of synthetic AVP (called desmopressin) which can cause low sodium levels and even seizures.
What causes AVP-Deficiency and AVP-Resistance?
AVP-Deficiency and AVP-Resistance can be inherited or acquired. Approximately one in three cases have no clear, definable cause. The recognised causes that should be looked for include the following:
- In AVP-Deficiency, the brain produces little or no AVP. This can be as a result of:
- Head injuries, pituitary tumours or neurosurgery (in these patients, AVP-Deficiency may only be short-term).
- Conditions that spread through the body (known as infiltrating) such as haemochromatosis (where patients accumulate too much iron in the body) and sarcoidosis (where patients have clumps of immune cells in several organs).
- Infections such as tuberculosis (a lung infection caused by bacteria called Mycobacterium tuberculosis bacteria) and meningitis (bacterial or viral infection in the central nervous system).
- In very rare cases, genetic defects (very rare).
- In AVP-Resistance, the brain is producing enough AVP but the kidneys are insensitive to it and are unable to concentrate urine. Common causes are kidney disease and abnormal electrolytes such as low potassium or high calcium levels in the blood.
- Gestational AVP-Deficiency – this only occurs in pregnancy and is usually due to enzymes produced from the placenta breaking down anti-diuretic hormone.
What are the signs and symptoms of AVP-Deficiency and AVP-Resistance?
The symptoms include:
- Too much urine production (called polyuria) ranging from 3–18 litres a day (anything more than 50ml/Kg/day is considered abnormally high). Effectively, this means that the patient will need to go to the toilet a lot.
- Excessive thirst (called polydipsia). This means that the patient will need to drink considerably more than normal.
- Passing urine too often at night (called nocturia). This will affect sleep as the patient will need to get out of bed frequently during the night to pass urine.
These symptoms are similar to those of diabetes mellitus, but there is no sugar present in the urine and blood sugar levels are normal.
Providing there is adequate provision of water to satisfy the excess thirst, the signs of AVP-Deficiency and AVP-Resistance can be minimal. Dehydration can occur if fluid intake cannot keep pace with the amount of urine passed. This can result in an imbalance of electrolytes in the blood, possibly causing symptoms such as headache, fatigue or muscle pain.
How common are AVP-Deficiency and AVP-Resistance?
AVP-Deficiency and AVP-Resistance are rare in the general population, affecting approximately one in 25,000 people. In patients who have had pituitary surgery, 10–20% can experience symptoms temporarily after the operation. A similar percentage of patients who have had a severe head injury develop short-term AVP-Deficiency. A minority of individuals have persistent symptoms after pituitary surgery and head injury.
Are AVP-Deficiency and AVP-Resistance inherited?
In most cases AVP-Deficiency and AVP-Resistance are not inherited. Very rarely, they can be due to inherited conditions such as a mutation (defect) in the genes that produce anti-diuretic hormone or faults in the genes that produce receptors (which normally recognise vasopressin) within the kidney cells that enable anti-diuretic hormone to function.
How are AVP-Deficiency and AVP-Resistance diagnosed?
Certain blood and urine tests can point to a diagnosis of Vasopressin Related Polyuria, but usually the baseline tests are normal. The key to making the diagnosis is in taking a good history and confirming the presence of polyuria (more than 50ml/kg/day) as well as dilute urine.
In patients that are unwell and very dehydrated, there may be a high sodium level (called hypernatraemia) and high concentration of the blood (serum or plasma osmolality), along with a low urine concentration (urine osmolality).
To be certain, a ‘water deprivation test’ can be undertaken, but these have been replaced by better and less unpleasant tests based on the measurement of a peptide called Co-peptin which gives an estimation of AVP levels.
What happens during a Water Deprivation Test (WDT)?
A water deprivation test takes several hours and involves attending hospital early in the day and being deprived of any fluid intake.
First part of the water deprivation test:
Initial blood and urine tests are done to measure the concentration and salt levels in both. At hourly intervals, the same tests are repeated along with measurements such as blood pressure, weight and the amount of urine passed. If the blood sodium or concentration levels rise significantly above normal along with low urine concentration, then it is likely that the patient has Vasopressin Related Polyuria.
Second part of water deprivation test:
To test if the patient has AVP-Deficiency or AVP-Resistance, an injection of desmopressin (a manufactured form of anti-diuretic hormone) is given. An hour after this injection is given, the urine concentration is tested again. If there is an increased concentration of more than 50% then AVP-Deficiency is most likely. Patients with AVP-Resistance will have a poor response to the desmopressin injection.
Co-peptin based tests:
Water Deprivation Tests are very unpleasant if a person has AVP-Deficiency or AVP-Resistance. There are newer ways of confirming the diagnosis such as by the measurement of a vasopressin-related substance called Co-peptin. Co-peptin is one of the breakdown products of AVP. A low level indicates AVP-Deficiency whilst a high level indicates AVP-Resistance. In borderline cases there are Co-peptin stimulation tests, the most accurate being the hypertonic saline test.
Imaging tests:
If AVP-Deficiency is diagnosed, an MRI scan of the head may be performed to look for any obvious abnormality in the hypothalamus (the region of the brain which makes anti-diuretic hormone) or in the pituitary gland (which releases anti-diuretic hormone).
In AVP-Deficiency there may the absence of the posterior pituitary bright spot (a bright area seen on certain types of brain scans and usually indicates the presence of AVP) which indicates the lack of AVP-secreting neurones).
How is AVP-Deficiency treated?
In mild cases of AVP-Deficiency (where the amount of urine passed per 24 hours is around 3-4 litres), treatment is not always needed. Those patients might just need to increase the amount of water they drink to compensate for the increased fluid loss through urination.
In more severe cases of AVP-Deficiency, patients can be prescribed with desmopressin, a manufactured version of anti-diuretic hormone, by the GP or an endocrinologist. Desmopressin can be given in the form of a nasal spray or a tablet. The dose given and how often medication needs to be taken, will depend on the severity of AVP-Deficiency and the symptoms the patient has. Desmopressin works in the same way as anti-diuretic hormone but is less easily broken down in the body.
How is AVP-Resistance Treated?
In mild cases of AVP-Resistance, patients may be asked to reduce the intake of salt and protein in their diet so that the kidneys will produce less urine. Similar to the patients with mild cases of AVP-Deficiency, patients with AVP-Resistance will also be suggested to drink more water to prevent severe dehydration.
In severe cases of AVP-Resistance, a water tablet (diuretic) called hydrochlorothiazide or amiloride may help, but desmopressin will not (as the body is irresponsive to anti-diuretic hormone). Diuretic drugs may be prescribed in combination with a non-steroidal anti-inflammatory drug (NSAID) called ibuprofen, to further reduce the amount of urine passed over time.
Are there any side-effects to the treatment?
Side-effects are very rare and vary depending on the treatment. Too much desmopressin can lead to low salt levels in the blood and a gathering of excess fluid in the body. This occurs because the desmopressin prevents the kidneys from excreting enough urine. These patients may experience headaches, nausea and vomiting. On the other hand, patients who are prescribed with diuretics and NSAIDs may experience dizziness and indigestion.
It is important to note that if the patient is concerned about any side-effects, he or she should talk to their endocrinologist or GP.
What are the longer-term implications of AVP-Deficiency?
With appropriate treatment, patients with AVP-Deficiency should be able to pursue a normal lifestyle. However, it is possible they will require long-term monitoring by their GP and/or endocrinologist. Patients need to be careful to avoid dehydration. In AVP-Deficiency, desmopressin is a life-sustaining therapy and should only be stopped following specialist advice, especially when patients are admitted to hospital for any reason.
It is really important that health professionals know when someone has AVP-Deficiency as they must be given fluids and desmopressin to prevent severe dehydration.
Are there patient support groups for people with AVP-Deficiency?
Pituitary Foundation may be able to provide advice and support to patients and their families dealing with AVP-Deficiency.