Diabetes Insipidus
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Direct answer
Diabetes insipidus is a disorder of water balance producing large volumes of dilute urine, typically more than 3 litres a day, because antidiuretic hormone is deficient or ineffective. Central diabetes insipidus means the pituitary secretes too little vasopressin, and a water deprivation test followed by desmopressin separates it from primary polydipsia and nephrogenic forms. Head injury, neurosurgery and hypothalamic or pituitary tumours are among the commonest causes.
What you must remember
- Central DI: vasopressin deficiency; urine concentrates after desmopressin.
- Nephrogenic DI: vasopressin resistance; urine stays dilute after desmopressin.
- Primary polydipsia: low plasma osmolality, with urine that concentrates during water deprivation.
- Causes of central DI: head injury, neurosurgery, craniopharyngioma, germinoma, metastases, tuberculous meningitis and sarcoidosis.
- Desmopressin response: a rise in urine osmolality of about 50 per cent or more suggests central DI.
- Water deprivation test: supervised; stopped when weight falls about 3 per cent or plasma sodium moves outside the safe range.
- Treatment: desmopressin, with fluid intake guided by thirst to avoid hyponatraemia.
A 26-year-old after a skull base fracture
A 26-year-old man had a basal skull fracture three weeks ago and now passes six litres of urine a day. His serum sodium is 149 mmol/L and plasma osmolality is 302 mOsm/kg, with urine osmolality of 180 mOsm/kg.
- Run the supervised test: A supervised water deprivation test is performed. Over six hours his plasma osmolality rises to 312 mOsm/kg, his weight falls by about 2.5 per cent, and urine osmolality stays at about 200 mOsm/kg.
- Give desmopressin: Desmopressin is then given, and urine osmolality rises to about 520 mOsm/kg, an increase of well over 50 per cent. This pattern is central diabetes insipidus.
- Check the other axes: Before treatment, the rest of the pituitary axes are checked with cortisol, thyroid function, gonadal hormones, prolactin and IGF-1, because pituitary injury often affects more than one axis.
- Start desmopressin safely: Oral desmopressin is started, and fluid intake is guided by thirst so that sodium is kept in range. Serum sodium is checked regularly, since excessive desmopressin or excessive water intake can produce hyponatraemia.
- Image the pituitary: An MRI of the pituitary and hypothalamus is useful for the cause and for the follow-up of the stalk.
Where the exam tries to catch you
Diabetes insipidus questions are dominated by a few look-alikes and misreadings.
- Trap: Calling every polyuric patient diabetes insipidus. Correct: Primary polydipsia mimics it, but plasma osmolality is low and urine concentrates during water deprivation, so the test distinguishes the two.
- Trap: Mistaking nephrogenic for central diabetes insipidus. Correct: Central DI shows a clear rise in urine osmolality after desmopressin, whereas nephrogenic DI does not.
- Trap: Missing transient diabetes insipidus in pregnancy. Correct: It is caused by placental vasopressinase, which breaks down vasopressin, and usually resolves after delivery.
- Trap: Overdosing desmopressin in a patient who drinks freely. Correct: This is a recognised cause of hyponatraemia that candidates should anticipate.
A partial central deficiency can respond only partly to desmopressin, so a weak response does not exclude the diagnosis.
Frequently asked questions
What is the diagnostic value of the water deprivation test in diabetes insipidus?
The water deprivation test shows whether urine concentrates when plasma osmolality rises, which distinguishes diabetes insipidus from primary polydipsia. In diabetes insipidus, urine osmolality stays low despite raised plasma osmolality. Desmopressin is then given to separate central from nephrogenic forms.
How does urine osmolality respond to desmopressin in central diabetes insipidus?
In central diabetes insipidus, urine osmolality rises by about 50 per cent or more after desmopressin because the kidney still responds to the drug. This rise confirms vasopressin deficiency. Nephrogenic diabetes insipidus shows little or no rise.
Which pituitary and hypothalamic disorders can cause central diabetes insipidus?
Craniopharyngioma, germinoma, metastases, pituitary surgery, head injury, sarcoidosis and tuberculous meningitis can cause central diabetes insipidus. Histiocytosis and infiltrative disorders are also recognised. Investigation usually includes MRI and assessment of other pituitary axes.
How is primary polydipsia distinguished from central diabetes insipidus?
Primary polydipsia has low plasma osmolality and urine that concentrates during a water deprivation test, whereas central diabetes insipidus has raised plasma osmolality with dilute urine. The desmopressin response is also normal in primary polydipsia. Careful history and the water deprivation test together make the distinction.
What is the first-line treatment for central diabetes insipidus?
Desmopressin is the first-line treatment for central diabetes insipidus and is available in intranasal, oral and injectable forms. The dose is individualised to control urine output. Sodium is monitored because excess desmopressin or water intake can cause hyponatraemia.