Diabetes Insipidus

Contents

What is Diabetes Insipidus?

Diabetes Insipidus (DI) is a condition where there is an excessive production of diluted urine. Most people with DI are also very thirsty and drink large amounts of water. It should not be confused with Diabetes Mellitus, often referred to as ‘sugar diabetes’, which is a problem with the way insulin is produced or handled by the body. The word ‘diabetes’ means ‘to siphon’ or to ‘pass through’, and this term refers to the increased amount of urine produced by the body. The word ‘insipidus’ means ‘diluted’ or ‘weak’, and this was coined when doctors in ancient Greece performed taste-tests on the urine of their patients and found that the urine in DI was tasteless!


DI may be ‘central’, where the problem that causes DI is in the brain. It may also be ‘nephrogenic’, where the problem is with the kidneys inability to concentrate urine. Some people produce a lot of urine because they drink too much fluid and this is known as ‘psychogenic polydipsia’. These people do not have DI because if they stopped drinking, the amount of urine they make would decrease. People with DI cannot stop passing large amounts of urine even if they stop drinking and this can make them dehydrated and unwell.

Control of blood concentration:

The concentration or osmolality of blood is controlled by the human brain. An area of the brain known as the hypothalamus is able to sense that the blood is too concentrated and produce a hormone called arginine vasopressin or antidiuretic hormone (ADH). The ADH is then released into the bloodstream by another part of the brain, the posterior pituitary. The kidney is then able to respond to the ADH in the bloodstream by increasing the amount of water that is reabsorbed and kept in the circulation. When the blood becomes more diluted (the osmolality decreases), the hypothalamus stops the production and release of ADH and the kidneys are able to release more water into the urine.


The hypothalamus and pituitary are very important parts of the brain. The hypothalamus is important for many bodily functions, including thirst, hunger, sleep, body temperature, nervous system responses and hormone synthesis and secretion. The posterior pituitary, along with secreting ADH, also secretes a hormone called oxytocin which is involved in pregnancy and breastfeeding.

Nephrogenic Diabetes Insipidus
The majority of this article will discuss central DI. Only a brief explanation of nephrogenic DI is provided here. In nephrogenic DI, the receptors that usually allow the kidney to react to ADH are not properly working. The brain will continue to make large amounts of ADH, however no matter how much ADH is in the body the kidneys are not able to respond to it. This form of DI is usually genetic, meaning that it is passed down in families and therapy involves medications other than ADH.

Central Diabetes Insipidus
In central DI there is a lack of ADH in the body. The brain is not able to properly respond to an increased blood concentration by secreting ADH. In contrast to nephrogenic DI, the kidneys are still able to respond normally to ADH in the bloodstream.

Causes of Central Diabetes Insipidus in children

Central DI is usually the result of damage to or abnormal development of the hypothalamus. DI can also be passed down in families, although this is much less common. Causes of DI include:
  • Congenital hypopituitarism with or without optic nerve hypoplasia
  • Langerhan’s cell histiocytosis
  • Head injury
  • Inherited problems -  abnormalities in the gene responsible for making ADH as part of a syndrome such as Wolfram syndrome
  • Pituitary stalk damage after surgery (more common in adults)
  • Inflammatory conditions – lymphocytic hypophysitis associated with pituitary cystic lesions or hypothalamic tumours such as germinoma

In a large Australian Paediatric Endocrinology clinic, central DI was due to head trauma (approximately 21%), familial causes (21%), tumours of the central nervous system (13%), malformations of the central nervous system (10%), histiocytosis (7%), hypoxia (5%) and infection (5%), with 18% of cases undiagnosed. In an Italian cohort, approximately 51% of central DI was due to an unknown cause, 23% due to intracranial tumour, 15% due to histiocytosis, 6% familial, 3% due to head trauma and 1% due to autoimmune polyendocrinopathy.


Symptoms of Diabetes Insipidus

DI is usually easier to diagnose in older children and those who are able to verbally express their complaints.

In these people, DI typically causes symptoms including:

  • Extreme thirst, particularly for ice-cold fluids
  • Frequent passage of urine
  • Bed-wetting, especially in a child who was previously dry at night


 In younger children and those unable to complain of thirst, DI may cause a variety of general symptoms such as:

  • Irritability
  • Vomiting
  • Fever
  • Frequent, very wet, overflowing nappies
  • Poor growth


 The non-specific nature of these symptoms means that DI is often more difficult to diagnose in young children and those unable to speak.

Complications of DI

Young children and those unable to speak are more at risk of developing complications of DI. Also at increased risk are those children with DI who are unable to sense thirst. These children have often had a craniopharyngioma, other brain tumours or brain injury affecting the hypothalamus. All these patient groups are unable to react to the increased blood concentration by increasing their fluid intake, putting them at increased risk of complications.

Potential complications of DI include:

  • Dehydration
  • Poor growth, as children with excessive fluid intake have no room left for food
  • Electrolyte abnormalities -  the passage of large amounts of undiluted urine causes an increase in the sodium (often called salt) concentration of the blood (known as hypernatraemia) this may result in seizures and damage to the brain
  • Overhydration – especially if hospitalised and given intravenous fluids that cannot be passed as urine if on DI medication (see below).

Diagnosis of DI

In DI, the urine is diluted, known as a low urine osmolality. At the same time, the blood is very concentrated and has a high plasma osmolality. A low urine osmolality at the same time as a high plasma osmolality is diagnostic for DI.

To confirm the diagnosis, patients may be asked to take a water deprivation test. In this test, patients will be brought into hospital after breakfast. No water will be given. Doctors and nurses will monitor the patient’s blood and urine concentration very regularly. They will also frequently weigh the patient and check how much urine they are producing. If the patient is unable to reduce the amount of urine they produce after stopping drinking, this will cause the plasma osmolality to rise further whilst the urine will be unchanged. If this occurs, the patient will be given a dose of synthetic or artificial ADH. This helps to separate the diagnoses of central and nephrogenic DI.


In central DI, there is a lack of ADH produced but the kidneys are ready to respond to ADH, so that a dose of ADH from outside the body will stimulate the kidneys to concentrate the urine. In nephrogenic DI, there is already ADH in the body however the kidneys are unable to react to it, so a dose of extra ADH will not help and diluted urine will continue to be produced. This sounds relatively simple in theory, however in practice many patients have ‘partial’ DI meaning that there is some ADH present in the body but not enough to properly concentrate the urine. These patients may concentrate their urine a little during the test and may not have as marked a response to extra ADH, making diagnosis a little more difficult.
As DI is often due to an abnormality or trauma to the brain, most doctors will suggest an MRI scan of the brain.

Treatment of Diabetes Insipidus

Synthetic ADH (DDAVP – D-arginine vasopressin) is available for the treatment of DI. It may be given as a tablet, a spray up the nose or through an intravenous drip in hospital.


A healthy diet is also important in DI. A low salt, low protein diet is often recommended. More fluids will be required in certain situations, such as extreme heat, exercise and illness. Parents should also monitor their children’s fluid intake and urine output.


For patients who are unable to sense thirst, a fluid ‘prescription’ is required from the doctor or dietician. These patients are unable to control their fluid intake at all which puts them more at risk of complications of DI. The fluid prescription is usually a fixed amount of fluid that needs to be given over the course of the day, with changes in fluid intake for situations such as extreme weather, exercise and illness.


Caring for children when they are sick can be complicated for those who have DI. When children have a fever, a frequent cough, have diarrhoea or are vomiting they will require more fluids. Young children and those unable to sense thirst are particularly at risk. Children should be given access to free water and encouraged to drink, but should not be force-fed fluids. If the child is unable to tolerate fluids or appears very unwell they should be reviewed urgently by a doctor. Their hydration level should be checked and they may require blood tests to review blood sodium content. It is important to tell the doctor that the child has DI and they are being treated with DDAVP, as this may change the way fluids are given to the child.


If children are at school, it is important to tell the teacher that they have DI. The teacher should be encouraged to allow extra toilet breaks and can assist the parents in monitoring fluid intake and output. Children should be encouraged to wear a medical alert such as a bracelet, so that in the event of an emergency the persons caring for the child will know that they have DI.


It is important for children with DI to be seen regularly by their specialist to monitor how well DDAVP is working. It is also very important to take the DDAVP exactly the way it is prescribed by the doctor. Too much DAVP will cause the body to retain fluid. This will cause the body sodium to go too low, which can cause serious symptoms such as seizures. If the DDAVP dose is too low, this will mean the symptoms of DI will still be present and there is a risk of dehydration.

SUMMARY
DI may be central or nephrogenic. In central DI, the brain is unable to respond to an increased blood concentration (plasma osmolality) by producing ADH as it normally would. In nephrogenic DI, the brain is able to produce ADH however the kidney is unable to respond to the presence of ADH in the circulation.


The most common symptoms of DI are extreme thirst and the passage of large amounts of urine. Young children are not able to express these symptoms. There are also some patients with an abnormality of the brain that makes them unable to sense thirst. These groups of patients have non-specific symptoms such as dehydration, irritability, fever and poor growth. They may also present with complications of DI such as high blood sodium causing seizures.

DI is usually diagnosed by a water deprivation test. Even when water is withheld, children with DI are unable to reduce the amount of urine they produce. A dose of synthetic ADH (DDAVP) will help distinguish between central and nephrogenic DI. An MRI scan may also be performed to look at the patient’s brain.


Children with central DI are treated with Desmopressin. They should also have their fluid intake and output monitored. Young children and those unable to sense thirst will require a fluid prescription. Sick day management of children with DI can be difficult and it is important to tell the doctor that the child has DI and is taking DDAVP. Regular contact with a health professional is important. 


References:
APEG Hormones and Me Booklet Series. Diabetes Insipidus. 2000
APEG Hormones and Me Booklet Series. Craniopharyngioma. 2000
Melmed S et al. Williams Textbook of Endocrinology 12th Edition 2011. Elselvier Saunders
Sperling MA. Pediatric Endocrinology 3rd Edition 2008. Elselvier Saunders
Al-Agha AE et al. Acquired central diabetes insipidus in children: a 12-year Brisbane experience. Journal of Paediatrics and Child Health 2001; 37(2): 172-5
Maghnie M et al. Central diabetes insipidus in children and young adults. New England Journal of Medicine 2000; 343(14): 998-1007