Diabetes insipidus - Causes of diabetes insipidus

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

ADH is produced by the hypothalamus and it's 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.

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 ADH to conserve water and stop the production of urine.

However, in 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 doesn't 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 don't respond to it in the normal way.

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

Cranial diabetes insipidus

The three most common causes of cranial diabetes insipidus are:

a brain tumour that damages the hypothalamus or pituitary gland – this accounts for around one in four cases
a severe head injury that damages the hypothalamus or pituitary gland – this accounts for around one in six cases
complications that occur during brain surgery – this accounts for one in five cases

No cause can be found for about a third of all cases of cranial diabetes insipidus. These cases, known as idiopathic, appear to be related to the immune system attacking healthy brain tissue by mistake. It's unclear what causes the immune system to do this.

Less common causes of cranial 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 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. In nephrogenic diabetes insipidus this doesn't occur, leading to excessive thirst and urine production.

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 gene changes) have been identified that cause congenital nephrogenic diabetes insipidus.

The first, known as the AVPR2 gene mutation, is responsible for 90% of all cases of congenital diabetes insipidus. However, it's still rare, occurring in an estimated one in 250,000 births.

The AVPR2 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 that they no longer respond to ADH.

Just over half of all people on long-term lithium therapy will develop some degree of nephrogenic diabetes insipidus. Stopping lithium treatment will often restore 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.

Read more about the treatment of bipolar disorder.

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

Brain: The brain controls thought, memory and emotion. It sends messages to the body controlling movement, speech and senses.
Genetic: Genetic is a term that refers to genes, the characteristics inherited from a family member.
Kidney: Kidneys are a pair of bean-shaped organs located at the back of the abdomen, which remove waste and extra fluid from the blood and pass them out of the body as urine.
Pituitary gland: The pituitary gland is a pea-sized gland in the centre of the head, which hangs below the brain and produces hormones.