Diabetes insipidus is related to a hormone known as antidiuretic hormone (ADH). ADH is sometimes called vasopressin.
ADH is produced by the hypothalamus, a section in your brain that also controls mood and appetite. Until it is needed, ADH is stored in the pituitary gland, which is found just below your brain, behind the bridge of your nose.
The function of ADH is to regulate the level of water in your body by controlling the amount of urine that your kidneys produce. When the level of water in your body drops, your pituitary gland releases ADH to conserve water and stop the production of urine.
However, if you have diabetes insipidus, ADH fails to properly regulate your body's level of water, and allows too much urine to be produced and passed from your body.
In cranial diabetes insipidus, the body does not produce enough ADH, so excessive amounts of water are lost during urination.
In nephrogenic diabetes insipidus, ADH is produced at the right levels but, for a variety of possible reasons, the kidneys fail to respond to the ADH in the normal way.
Possible underlying causes for both types of diabetes insipidus are described below.
Causes of cranial diabetes insipidus
The three most common causes of cranial diabetes insipidus are:
- brain tumour that damages the hypothalamus or pituitary gland, which accounts for 25% of cases
- severe head injury that damages the hypothalamus or pituitary gland, which accounts for 16% of cases
- complications that occur during brain surgery, which account for 20% of cases
In about a third of cases, no apparent cause can be found for development of the condition. These types of cases, known as idiopathic cases, appear to be related to the immune system attacking healthy brain tissue by mistake. What causes the immune system to do this is unclear.
Less common causes of cranial diabetic insipidus include:
- cancers that spread from another part of the body, such as the lungs or the bone marrow, to the brain
- Wolfram syndrome, a rare genetic disorder that also causes sight and 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
Causes of nephrogenic diabetes insipidus
Your kidneys contain tubules called nephrons, which control how much water is reabsorbed into your body and how much is passed as urine.
In a healthy person, ADH signals to the nephrons to reabsorb water into the body. This does not occur in cases of nephrogenic diabetes insipidus, leading to the symptoms of constant thirst and excessive urine production.
The possible causes of nephrogenic diabetes insipidus are classed as either:
- congenital, which means the condition is present at birth
- acquired, which means the condition develops later in life due to an external factor
Congenital nephrogenic diabetes insipidus
Two genetic mutations (abnormal changes to the genes) have been identified that cause nephrogenic diabetes insipidus present at birth.
The first is known as the AVRP2 gene mutation and is responsible for 90% of all cases of congenital diabetes insipidus (although it is still very rare, occurring in an estimated 1 in every 250,000 births). This gene mutation can only be passed down by mothers (who are not 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
The most common cause of acquired nephrogenic diabetes insipidus is the medication lithium.
Lithium is widely used to treat bipolar disorder (manic depression), which is a mental health condition that can cause sudden and severe mood swings from a state of depression (feeling very sad) to a state of mania (feeling very happy and full of energy but acting irrationally).
Long-term use of lithium can damage the cells of the kidneys, meaning they no longer respond to ADH.
Just over half of all people on long-term lithium therapy will develop nephrogenic diabetes insipidus. Stopping treatment with lithium will often restore normal kidney function, though in many cases the damage to the kidneys is permanent.
Many people with bipolar disorder are willing to accept the risks associated with long-term lithium use as they feel they are outweighed by the improvement they experience with their mental health symptoms.
Due to the risks above, it is recommended that you have kidney function tests every three months if you are taking lithium. See the Health A-Z page on Bipolar disorder – treatment for more information.
Other causes of acquired nephrogenic diabetes insipidus include:
- hypercalcaemia, a condition where there is too much calcium in the blood (high calcium levels can damage the kidneys)
- hypokalemia, a condition where there is not enough potassium in the blood (all the cells in the body, including kidney cells, require potassium to function properly)
- the kidneys becoming damaged by infection (the medical term for kidney infection is pyelonephritis)
- ureteral obstruction, when one or both of the tubes that connect the kidneys to the bladder (the ureters) become blocked by an object such as a kidney stone, which can then damage the kidneys
