The inability to produce concentrated urine due to either antidiuretic hormone deficiency or resistance, which leads to extreme thirst and polyuria. The diagnosis may be confirmed using a water deprivation test.
If the clinical suspicion is low, and electrolytes, pituitary function, glucose and paired osmolalities are normal, the patient may be reassured and discharged.
If clinical suspicion remains after the initial investigations, and if any offending drugs have been removed, and electrolyte disturbances have been corrected, proceed to a formal water deprivation test. If this is normal, the patient should be reassured and discharged with advice.
If water deprivation test is diagnostic of diabetes insipidus, start treatment.
Long term treatment is usually given as an intranasal spray (typical dose 1-2x10mcg inhalations on retiring).
Mild cases may be controlled with oral desmopressin (typical dose 100-300mcg on retiring), and top up oral doses may also be added during the day in those whose symptoms are not fully controlled with once daily treatment.
In patients with a normal thirst mechanism, treatment aims to relieve nocturia and extreme thirst. A short period of polyuria and thirst is allowed just before a dose to prevent water overload developing and to maintain normal serum biochemistry.
Long term monitoring of symptoms, urea and electrolytes, is usually all that is required. Hyponatraemia indicates excessive replacement, which should prompt consideration of dose reduction.
In patients with extensive hypothalamic damage and loss of the normal thirst mechanism, it may be necessary to calculate a fixed oral intake and DDAVP dose. This requires very close monitoring of fluid input and output as well as serum and urine biochemistry at the start of treatment. This should usually occur within a supervised hospital environment.
A formal water deprivation test is not necessary before starting treatment in the acute setting, for example in the hours or days following pituitary surgery. In this situation, if the patient is polyuric as evidenced by passing >150mls urine for two successive hours, serum electrolytes and spot urine and plasma osmolalites should be tested. If these are consistent with DI, start emergency treatment with subcutaneous doses of desmopressin (typical dose 1mcg).
Urea and electrolytes and paired urine and serum osmolalities should be performed daily in the acute phase to confirm the need for ongoing treatment and to prevent over-treatment.
Arrange clinical review, ideally by an endocrine specialist nurse, within a week to ensure that symptoms are controlled and to reassess serum electrolytes and paired osmolalities.
In patients on replacement therapy, nasal desmopressin tends to control symptoms for approximately 16 hours. Symptoms occurring before this time require an increase in the size or frequency of desmopressin dose.
If the patient does not experience at least a short period of thirst during the day, they are at risk of over-replacement and water overload. This should prompt dose reduction, as should hyponatraemia.
Where hypopituitarism is confirmed, hormone replacement therapy should be started immediately with glucocorticoid replacement therapy taking priority over all other treatments.
If there is possible GH or ACTH deficiency perform insulin, arginine-GHRH or glucagon stress testing.
Ensure that investigations into the cause of DI have been arranged and discussed in a multidisciplinary setting. Pituitary MRI scan, pituitary function, serum angiotensin converting enzyme, alfa feto protein, human choriotropic hormone, auto-antibody screen and chest radiograph are the minimum investigations required in all cases.
Future management depends on underlying diagnosis.
If no underlying diagnosis has been reached - baseline and dynamic pituitary function, MRI scan, tumour markers and auto-antibody screen are all normal - the patient will require a thorough review at a multidisciplinary meeting. They will then require clinical follow up within a week, then at three and six months with repeat electrolytes before each visit. Annual review thereafter is usually satisfactory.
Imaging is usually repeated on at least one further occasion, even where the initial results appear to be normal. The timing of this should be determined by the multidisciplinary team.
Blood pressure, volume status, symptoms and electrolytes and osmolalities should be assessed annually.
Ask the patient how long their thirst is controlled for after a dose of desmopressin, and how they felt if they have ever missed a dose. Nasal desmopressin tends to control symptoms for approximately 16 hours. Symptoms occurring before this time require an increase in the size or frequency of desmopressin dose. Lack of thirst and passage of very little urine may suggest over-replacement.
Pituitary function should also be repeated annually with dynamic testing as indicated. Repeat MRI scanning should be considered in all cases at one year or as determined by the multidisciplinary team.
This is usually managed by renal physicians.
Where this is secondary, the underlying cause should be treated i.e. remove the causative drug, or correct the electrolyte abnormality.
Where this is familial or idiopathic, standard treatment is with hydrochlorothiazide or amiloride but this is often unsatisfactory.
Non-steroidal anti-inflammatory drugs may also improve symptoms in some cases.
If there is a partial response to desmopressin on water deprivation testing, it may be appropriate to try high dose desmopressin.