Professor Peter Baylis
University of Newcastle

Normal water balance in the body is controlled principally by Anti-diuretic Hormone (ADH), which is synthesised in the Hypothalamus and released by the posterior Pituitary gland, a healthy kidney responsive to ADH and an intact thirst mechanism. When water is lost from the body, the concentration of sodium in the blood rises. This stimulates the release of ADH, which acts on the kidneys to stop the water loss. Our urge to drink also increases when sodium levels in the blood rise. When sodium levels fall below normal, the pituitary gland switches off ADH release, and the kidneys increase the amount of water passed in urine.

Hypothalamic Diabetes Insipidus (DI) is a disorder of urine concentration which results from deficient secretion of ADH. This causes the passage of large volumes of dilute urine (polyuria) and an excessive thirst (polydipsia). Some of the common causes are trauma (head injury, neurosurgery), tumours (pituitary tumours) and infection (meningitis); other cases are Idiopathic (cause unknown). In some patients DI will last only for 24 hours following surgery or can even last for 2-4 years and then resolve, although this is rare.

Investigations

1. Prior to carrying out specific tests for DI, urine volume should be measured; more than 3 litres should be passed in 24 hours before proceeding to further tests.
2. Water deprivation test, plus administration of Desmopressin (DDAVP): the patient is allowed to drink normally overnight and then deprived of fluid for up to 8 hours. During this test the patient is carefully monitored, weighed regularly, has blood sampled every 4 hours, and urine volume and osmolality checked every 2 hours. After dehydration the patient is given DDAVP and urine volume and osmolality are again measured overnight for about 16 hours.
3. In a small number of endocrine units, ADH levels in the blood are measured whilst the patient is given an infusion of hypertonic saline; this test takes 2 hours.
4. If ADH levels cannot be measured or the results of water deprivation are equivocal, the patient may be given a trial of low dose DDAVP for 2 weeks. Close supervision is needed during this time.

Some people have excessive thirst which is not due to ADH deficiency. This can be diagnosed using a test dose of DDAVP. If they continue to drink excessively their serum sodium level falls. This can be caused by a hypothalamic tumour or by certain drugs which cause a dry mouth. Lack of response to ADH by the kidney also causes polyuria.

Treatment

Mild DI (urine volume of less than 4 litres per 24 hours) may not require any therapy; patients should drink sufficient fluids to quench their thirst. DDAVP, the treatment of choice, is usually taken orally (100-1,000 mg per day) or intranasally (10-120 g per day) in divided doses. Some people cannot control their DI with oral DDAVP because it is absorbed erratically through the digestive system. Rates of absorption can vary from day to day and can be affected by what has been eaten etc; this can cause variation in control. If too much DDAVP is taken, you will be unable to pass adequate amounts of urine and may notice an increase in your weight. If this happens you should reduce the amount you drink and wait for the effects of DDAVP to wear off. Dr Baylis advises his patients to regularly have a day when they reduce their DDAVP and so pass large volumes of urine, to prevent chronic overdose of the drug.

Hyponatraemia

Having too little sodium in the blood (hyponatraemia) can be dangerous. The patient will feel very ill and may suffer cramps, nausea, fits and eventually coma. Hyponatraemia can be caused by taking too much DDAVP, or by drinking more than usual whilst taking the same amount of DDAVP.

Comments from the audience

1. If going out for the evening at the pub, don't take DDAVP until all the fluids consumed have been passed out in urine, to avoid hyponatraemia.
2. Desmospray may be stored at room temperature (up to 25C). However, DDAVP/Desmopressin Intranasal and DDAVP/Desmopressin Injection still need to be refrigerated.
3. It is possible to get a disabled toilet key from social services.
4. More help and advice can be sought through local continence advisors.
5. Some insurers do not distinguish between DI and diabetes mellitus, so leading to increased premiums.
   Professor Baylis advised that you should inform the companies that you have 'Vasopressin or ADH deficiency'.