Diabetes Insipidus

Question 1

What is diabetes insipidus?

Answer 1

Diabetes insipidus is a lack of antidiuretic hormone (ADH) or a lack of response to ADH.

This prevents the kidneys from being able to concentrate the urine leading to polyuria (excessive amounts of urine) and polydipsia (excessive thirst).

It can be classified as nephrogenic or cranial.

Question 2

Nephrogenic Diabetes Insipidus

What is it?

Causes?

Answer 2

Nephrogenic diabetes insipidus is when the collecting ducts of the kidneys do not respond to ADH. It can also be caused by:

Causes:
- Drugs, particularly lithium used in bipolar affective disorder

• Mutations in the AVPR2 gene on the X chromosome that codes for the ADH receptor
• Intrinsic kidney disease
• Electrolyte disturbance (hypokalaemia and hypercalcaemia)

Question 3

Cranial Diabetes Insipidus

What is it?

Causes?

Associations

Answer 3

Cranial diabetes insipidus is when the hypothalamus does not produce ADH for the pituitary gland to secrete.

Causes:
Idiopathic
Brain tumours
Head injury
Brain malformations
Brain infections (meningitis, encephalitis and tuberculosis)
Brain surgery or radiotherapy

Associated with Sarcoidosis (erythema nodusum, dry cough, bilateral hilar lyphadenopathy)

Question 4

Clinical Features

Answer 4

Polyuria (excessive urine production)
Polydipsia (excessive thirst)
Dehydration
Postural hypotension
Hypernatraemia

Question 5

Investigations

Answer 5

Low urine osmolality
High serum osmolality
Water deprivation test (a.k.a desmopressin stimulation test)

Question 6

Water deprivation test (a.k.a desmopressin stimulation test)

Method

Answer 6

Fluid deprivation: patient not to have any fluids for 8 hours before the test

Urine Osmolality measured

Then desmopressin (synthetic ADH) given

Then 8 hours later: urine osmolality measured

Question 7

Water deprivation test results

Cranial vs nephrogenic DI

Answer 7

Cranial diabetes insipidus: The kidneys are still capable of responding to ADH.
- Initially the urine osmolality remains low as it continues to be diluted by excessive water secretion in the kidneys.

• Then when synthetic ADH is given the kidneys respond by reabsorbing water and concentrating the urine so the urine osmolality will be high.

Nephrogenic diabetes insipidus: patient is unable to respond to ADH
- Therefore the urine osmolality will be low initially and remain low even after the synthetic ADH is given.

Question 8

Management

Answer 8

Cranial DI:

• MRI (head)
• test anterior pituitary function (p232)
• Give desm- opressin, a synthetic analogue of ADH (eg Desmomelt® tablets).

Nephrogenic:

• Treat the cause
• If it persists, try bendroflumethiazide 5mg PO/24h
• NSAIDS lower urine volume and plasma Na+ by inhibiting prostaglandin synthase: prostaglandins locally inhibit the action of ADH

Question 9

Emergency Management

Answer 9

• Do urgent plasma U&E, and serum and urine osmolalities
• Monitor urine output carefully and check U&E twice a day initially.
• IVI to keep up with urine output. If severe hypernatraemia, do not lower Na+ rapidly
  as this may cause cerebral oedema and brain injury
• If Na+ is ≥170, use 0.9% saline initially—this contains 150mmol/L of sodium. Aim to reduce Na+ at a rate of less than 12mmol/L per day. Use of 0.45% saline can be dangerous.
• Desmopressin 2mcg IM (lasts 12–24h) may be used as a therapeutic trial.