Diabetes insipidus

Question 1

The two main symptoms of diabetes insipidus are

Answer 1

polydipsia (thirst) and polyuria (need to pass urine very frequently)

Question 2

subtypes of diabetes insipidus

Answer 2

• Pituitary (cranial) diabetes insipidus, where there is an insufficiency of antidiuretic hormone (ADH) in the body
• Nephrogenic
  diabetes insipidus where the kidneys fail to respond adequately to ADH.

Question 3

Antidiuretic Hormone (ADH)

Answer 3

ADH is also known as vasopressin. The role of ADH is to regulate the amount of fluid in the
body, it is produced in the hypothalamus and then passes to the pituitary gland where it is
stored until needed.
ADH is released from the pituitary gland when the amount of water in the body is too low
and helps retain water in the body by reducing the amount of water excreted through the
kidneys. This results in the production of more concentrated urine.

Question 4

Causes of diabetes insipidus

Answer 4

The causes can be idiopathic, familial or vascular. It can be caused as a result of tumours, infections, infiltrations or inflammation. It may also occur post-surgery, post radiotherapy (cranial) or as a result of trauma.

Question 5

Diagnosis

Answer 5

This is derived from assessing symptoms, complex tests and investigations which may
include;
 Urinalysis
 Fluid deprivation test
 Anti-diuretic hormone (ADH) test
 MRI scan

Question 6

What can be used in the differential diagnosis of diabetes insipidus

Answer 6

• Desmopressin

Question 7

Pituitary (cranial) Diabetes Insipidus

Answer 7

This is the most common type of diabetes insipidus.

Causes; damage to the hypothalamus or pituitary gland, e.g. after a head injury or surgery.
However in 1 in 3 cases there is no identifiable reason as to why the hypothalamus stops producing ADH.

Question 8

Pituitary (cranial) Diabetes Insipidus - Treatment

Answer 8

In mild cases (if produce 3-4 litres of urine in 24 hours) pharmacological treatment may not be required. Instead, patients may be advised by an endocrinologist to increase the amount of fluid drunk each day in order to reduce symptoms. Treatment is with vasopressin by
subcutaneous or intramuscular injection. Desmopressin is also used for treatment and can
be given orally, sublingually, intranasally or by subcutaneous, intramuscular or intravenous
injection. See current BNF for side effects and usual dose regimens.
In partial pituitary diabetes insipidus benefit may be gained from the paradoxical
antidiuretic effect of thiazides e.g. chlortalidone. Carbamazepine is sometimes useful
(unlicensed use).

Question 9

Nephrogenic Diabetes Insipidus

Answer 9

In nephrogenic diabetes insipidus the renal tubules are resistant to normal or high levels of plasma vasopressin.

Question 10

Nephrogenic Diabetes Insipidus - causes

Answer 10

Nephrogenic diabetes insipidus may be familial, idiopathic or can be acquired as a result of renal disease, sickle cell disease, drug ingestion (e.g. lithium), hypercalcaemia or hypokalaemia

Question 11

Nephrogenic Diabetes Insipidus - treatment

Answer 11

Where possible reverse the cause.
In mild cases it may be possible to ease symptoms with dietary changes, for example
decreasing the amount of salt and protein in the diet will result in the kidneys producing less
urine. This should only be advised by an endocrinologist or GP. Benefit may be gained from
the paradoxical antidiuretic effect of thiazides, e.g. chlortalidone. See current BNF for
further information.

Question 12

What is diabetes insipidus (DI) and why do we get it?

Answer 12

Diabetes insipidus (DI) is caused by a problem with either the production, or action, of the hormone vasopressin (AVP). If you have DI your kidneys are unable to retain water. This leads to the production of large volumes of urine and, in turn, greatly increased thirst. DI can occur at any age, but is mostly found in adults. It is a rare disorder, affecting only about 1 in 25,000 people.

To understand DI we need to understand a little about how the body regulates water balance - the difference between how much water the body takes in and how much it passes out. Water balance is very important for the body. A large proportion of what we are is made up of water. In addition, the amount of water we have in our circulation is a large factor in determining the balance of salt in our bodies. As with any function that is important, the body has a sensitive mechanism for regulating water balance. Like any good mechanism it is also simple, involving two key components:
• Vasopressin (AVP or ADH - antidiuretic hormone) - which regulates the amount of water passed out of the body in urine.
• Thirst and drinking - which determines the amount of water the body takes in.

AVP (sometimes called Anti-diuretic hormone or ADH) is a hormone released from the rear most part of the pituitary gland (the posterior pituitary). This gland is located at the base of the brain, and is about 3 to 5 centimetres behind the bridge of the nose. AVP circulates in the bloodstream and acts on the kidneys to reduce the amount of water that is passed out in urine.

How AVP and thirst work together is best described with the help of the bath tub analogy. As with a bath tub, the body likes to keep the level of water it contains at the right level for its purposes. There are only two ways the level of water can be altered:
• Water can be let in to the bath through turning the taps on; just as thirst and drinking can allow more water into the body 4 Diabetes insipidus
• Water can be let out of the bath through taking the plug out; just as the body can let more water out by reducing the amount of AVP produced and so letting more water to be passed out of the body as urine

Unlike a bath tub, the body is very good at sensing the level of water it has on board. If it does not have enough and is dehydrated, it triggers us to drink more through activating the thirst (turning on the taps). At the same time, it makes more AVP and so reduces water loss in urine (it puts the plug in). On the other hand, if the body senses the level of water is too much, it turns the thirst off (turning taps off) and makes less AVP (taking the plug out of the plug hole). The level of water is therefore maintained through a combined approach.

Together, AVP and thirst maintain water balance very effectively in both situations where water is either easy to find, or is scarce. DI occurs when this mechanism regulating water balance breaks down

Question 13

How is it diagnosed?

Answer 13

What tests are carried out and how will these feel?
Investigation methods for patients with excessive urine production would be:
• Measurement of 24 hour urine output
• Measurement of plasma osmolality from a blood test (a measure of sodium and glucose circulating in the blood)
• Water deprivation test (described below)
• Therapeutic trial of desmopressin (DDAVP®)

Question 14

What can be used in the treatment of hyponatraemia resulting from inappropriate secretion of antidiuretic hormone, if fluid restriction alone does not restore sodium concentration or is not tolerable

Answer 14

Demeclocycline hydrochloride - Initially 0.9–1.2 g daily in divided doses, maintenance 600–900 mg daily.

Question 15

licensed for the treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion

Answer 15

Tolvaptan is a vasopressin V2-receptor antagonist - Initially 15 mg once daily, increased if necessary up to 60 mg once daily, a reduced starting dose of 7.5 mg once daily should be considered for patients at risk of overly rapid correction of serum-sodium concentration.