Alternative names for diabetes insipidus

DI; AVP deficiency

What is diabetes insipidus?

Diabetes insipidus is a condition caused by impaired body production of or response to anti-diuretic hormone (ADH). (also called vasopressin which is the term we will use in this article) is produced in the hypothalamus and then secreted by the pituitary gland into the bloodstream at the base of the brain.

Vasopressin stimulates the kidneys to produce more concentrated urine, thus reducing water loss and retaining water in the body. Vasopressin plays an important role in controlling the fluid balance in the body.
There are two main types of diabetes insipidus, cranial and nephrogenic. Cranial diabetes insipidus is a condition in which the hypothalamus does not produce enough anti-diuretic hormone and is the most common type. Nephrogenic diabetes insipidus is a condition in which the kidneys fail to respond to anti-diuretic hormone. Both conditions 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).

Other types of diabetes insipidus are gestational diabetes insipidus (which is experienced by some pregnant women) and primary polydipsia (caused by too much water intake).

Diabetes insipidus is not related to diabetes mellitus (’mellitus’ meaning ‘sweet’ and referring to high sugar levels that cause excess passing of urine).

What causes diabetes insipidus?

Both cranial and nephrogenic diabetes insipidus can be inherited or acquired. Approximately one in three cases of diabetes insipidus has no clear, definable cause. The recognised causes of diabetes insipidus that should be looked for include the following:

1. In cranial diabetes insipidus, the brain produces little or no vasopressin. This can be as a result of:

• head injuries, pituitary tumours or neurosurgery (in these patients, diabetes insipidus 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 (lung infection by bacteria called Mycobacterium tuberculosis bacteria) and meningitis (bacterial or viral infection in the central nervous system)
• genetic defects (very rare).

2. In nephrogenic diabetes insipidus, the brain is producing enough vasopressin but the kidneys are insensitive to it and are unable to concentrate the urine.

3. Gestational diabetes insipidus – this only occurs in pregnancy and is usually due to enzymes produced from the placenta breaking down anti-diuretic hormone.

4. In primary polydipsia, some individuals may have drunk too much water as they think drinking water is beneficial to their physical health.

What are the signs and symptoms of diabetes insipidus?

The symptoms of diabetes insipidus include:

1. Too much urine production (polyuria) ranging from 3–18 litres a day. Effectively, this means that the patient will need to go to the toilet a lot.

2. Excessive thirst (polydipsia). This means that the patient will need to drink considerably more than normal.

3. Passing urine too often at night (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 diabetes insipidus 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 is diabetes insipidus? 

Diabetes insipidus is 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 diabetes insipidus. A minority of individuals have persistent symptoms after pituitary surgery and head injury.

Genetic causes of diabetes insipidus are very rare.

Is diabetes insipidus inherited?

In most cases diabetes insipidus is not inherited. Very rarely, it 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 is diabetes insipidus diagnosed? 

Certain blood and urine tests can point to a diagnosis of diabetes insipidus such as a high sodium level (hypernatraemia) and high concentration of the blood (serum or plasma osmolality), along with a low urine concentration (urine osmolality).

To be certain of the diagnosis, a ‘water deprivation test’ was previously undertaken. This takes several hours and involves attending hospital early in the day and being deprived of any fluid intake. 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 diabetes insipidus.

To test if the diabetes insipidus is cranial or nephrogenic, 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 cranial diabetes insipidus is most likely. Patients with nephrogenic diabetes insipidus will have a poor response to the desmopressin injection.

These tests are very unpleasant if diabetes insipidus is truly present and there are newer ways of confirming the diagnosis such as by the measurement of a vasopressin-related substance called co-peptin.

If cranial diabetes insipidus 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).

How is diabetes insipidus treated?

In mild cases of cranial diabetes insipidus (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 cranial diabetes insipidus, 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 diabetes insipidus and the symptoms the patient has. Desmopressin works in the same way as anti-diuretic hormone but is less easily to be broken down in the body.

In mild cases of nephrogenic diabetes insipidus, 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 cranial diabetes insipidus, patients with nephrogenic diabetes insipidus will also be suggested to drink more water to prevent severe dehydration.

In severe cases of nephrogenic diabetes insipidus, 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 diabetes insipidus?

With appropriate treatment, patients with diabetes insipidus 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 cranial diabetes insipidus, 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 diabetes insipidus as they must be given fluids and desmopressin (in cranial D.I) to prevent severe dehydration.

Are there patient support groups for people with diabetes insipidus?

Pituitary Foundation may be able to provide advice and support to patients and their families dealing with diabetes insipidus. This is a move to change the name of diabetes insipidus to vasopressin deficiency and vasopressin resistance to avoid the confusion with diabetes mellitus.