Diabetes insipidus occurs due to:
- A lack of antidiuretic hormone (cranial diabetes insipidus)
- A lack of response to antidiuretic hormone (nephrogenic diabetes insipidus)
Antidiuretic hormone is produced in the hypothalamus and secreted by the posterior pituitary gland. It is also known as vasopressin. ADH stimulates water reabsorption from the collecting ducts in the kidneys.
With diabetes insipidus, the kidneys are unable to reabsorb water and concentrate the urine, leading to:
- Polyuria (excessive amounts of urine)
- Polydipsia (excessive thirst)
Primary polydipsia is when the patient has a normally functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria). This is not diabetes insipidus.
Nephrogenic Diabetes Insipidus
Nephrogenic diabetes insipidus is when the collecting ducts of the kidneys do not respond to ADH. It can be idiopathic, without a clear cause, or it can be caused by:
- Medications, particularly lithium (used in bipolar affective disorder)
- Genetic mutations in the ADH receptor gene (X-linked recessive inheritance)
- Hypercalcaemia (high calcium)
- Hypokalaemia (low potassium)
- Kidney diseases (e.g., polycystic kidney disease)
Cranial Diabetes Insipidus
Cranial diabetes insipidus is when the hypothalamus does not produce ADH for the pituitary gland to secrete. It can be idiopathic, without a clear cause, or it can be caused by:
- Brain tumours
- Brain injury
- Brain surgery
- Brain infections (e.g., meningitis or encephalitis)
- Genetic mutations in the ADH gene (autosomal dominant inheritance)
- Wolfram syndrome (a genetic condition also causing optic atrophy, deafness and diabetes mellitus)
Presentation
Presenting features of diabetes insipidus are:
- Polyuria (producing more than 3 litres of urine per day)
- Polydipsia (excessive thirst)
- Dehydration
- Postural hypotension
Investigations
Investigations show:
- Low urine osmolality (lots of water diluting the urine)
- High/normal serum osmolality (water loss may be balanced by increased intake)
- More than 3 litres on a 24-hour urine collection
The water deprivation test is the test of choice for diagnosing diabetes insipidus.
Water Deprivation Test
The water deprivation test is also known as the desmopressin stimulation test. Times may vary depending on the local protocol.
The patient avoids all fluids for up to 8 hours before the test (water deprivation). After water deprivation, urine osmolality is measured. If the urine osmolality is low, synthetic ADH (desmopressin) is given. Urine osmolality is measured over the 2-4 hours following desmopressin.
In primary polydipsia, water deprivation will cause urine osmolality to be high. Desmopressin does not need to be given. A high urine osmolality after water deprivation rules out diabetes insipidus.
In cranial diabetes insipidus, the patient lacks ADH. The kidneys are still capable of responding to ADH. Initially, the urine osmolality remains low as it continues to be diluted by the excessive water lost in the urine. After desmopressin is given, the kidneys respond by reabsorbing water and concentrating the urine. The urine osmolality will be high.
In nephrogenic diabetes insipidus, the patient is unable to respond to ADH. The urine osmolality will be low both before and after the desmopressin is given.
|
Urine Osmolality After Water Deprivation |
Urine Osmolality After Desmopressin |
|
|
Primary Polydipsia |
High |
Not required |
|
Cranial Diabetes Insipidus |
Low |
High |
|
Nephrogenic Diabetes Insipidus |
Low |
Low |
Management
The underlying cause should be treated (e.g., stopping lithium). Mild cases may be managed conservatively.
Desmopressin (synthetic ADH) can be used in cranial diabetes insipidus to replace the absent antidiuretic hormone. The serum sodium needs to be monitored, as there is a risk of hyponatraemia (low sodium) with desmopressin.
Nephrogenic diabetes insipidus is less straightforward to treat. Management options include:
- Ensuring access to plenty of water
- High-dose desmopressin
- Thiazide diuretics
- NSAIDs
Last updated March 2023
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