Diabetes Insipidus

Last updated 17 August 2026.

Key points

Diabetes insipidus (DI): passage of large volumes of dilute urine due to impaired ADH (vasopressin) secretion - cranial DI - or renal resistance to ADH - nephrogenic DI.
Cranial causes: idiopathic, pituitary or hypothalamic tumours, pituitary surgery or trauma, Sheehan syndrome, infiltrative disease, and familial forms.
Nephrogenic causes: lithium is the classic cause; also hypercalcaemia, hypokalaemia, chronic kidney disease and the X-linked AVPR2 mutation.
Presentation: polyuria, polydipsia and nocturia. Risk of severe dehydration and hypernatraemia if fluid access is restricted, e.g. post-operatively or with reduced consciousness.
Diagnosis: high or high-normal plasma osmolality with inappropriately dilute urine is the key clue. Confirm with a water deprivation test followed by desmopressin, which distinguishes cranial from nephrogenic DI.
Management: cranial DI - desmopressin. Nephrogenic DI - treat the cause (stop lithium if possible), thiazide diuretics, NSAIDs, and a low salt/protein diet.
Key differential: primary (psychogenic) polydipsia, where urine concentrates on fluid deprivation alone without desmopressin, and poorly controlled diabetes mellitus, where glucose drives an osmotic diuresis.
Danger of over-treatment: excess desmopressin causes dilutional hyponatraemia. DI can also occur transiently in pregnancy from placental vasopressinase.

Introduction

Diabetes insipidus is the passage of abnormally large volumes of dilute urine, caused either by impaired secretion of antidiuretic hormone (ADH, also called arginine vasopressin) from the posterior pituitary - cranial (central) DI - or by resistance of the renal collecting duct to ADH - nephrogenic DI.¹

Normally, ADH released from the posterior pituitary acts on V2 receptors in the renal collecting duct, inserting aquaporin-2 water channels and allowing water reabsorption. Without effective ADH action, the collecting duct remains impermeable to water, and large volumes of dilute urine are lost regardless of the body's hydration state.

Aetiology

Causes of cranial and nephrogenic diabetes insipidus.
Type	Causes
Cranial (central)	Idiopathic (up to half of cases); pituitary or hypothalamic tumours (craniopharyngioma, germinoma, pituitary adenoma); pituitary/hypothalamic surgery or trauma; traumatic brain injury; Sheehan syndrome; infiltrative disease - sarcoidosis, Langerhans cell histiocytosis, lymphocytic infundibulo-neurohypophysitis; infection - meningitis, encephalitis; familial - autosomal dominant AVP gene mutations; congenital malformations such as septo-optic dysplasia
Nephrogenic	Lithium - the classic and commonest acquired cause, affecting up to 40% of long-term users; hypercalcaemia; hypokalaemia; chronic kidney disease and tubulointerstitial disease; relief of chronic urinary tract obstruction; genetic - X-linked AVPR2 mutation (the majority of congenital cases, presenting in male infants) or autosomal aquaporin-2 (AQP2) mutation

The triphasic response after pituitary surgery

DI after trans-sphenoidal pituitary surgery classically follows three phases, and failing to anticipate the second phase leads to iatrogenic hyponatraemia.

Phase 1 (hours to days): DI - surgical trauma stuns the posterior pituitary/stalk, ADH release stops, and polyuria begins
Phase 2 (days 5-10): transient antidiuresis - stored ADH leaks uncontrollably from dying neurons, urine output falls, and desmopressin plus free water can cause dangerous hyponatraemia if not withdrawn or reduced
Phase 3: either permanent DI (if enough of the neurohypophysis is destroyed) or resolution, depending on the extent of injury
Because of this pattern, sodium and fluid balance need close monitoring for at least 1-2 weeks after pituitary surgery, not just in the first day or two

Diabetes insipidus in pregnancy is a distinct, usually transient entity: the placenta produces an enzyme, vasopressinase, that degrades circulating ADH. It typically resolves within weeks of delivery, and is managed with desmopressin, which is resistant to vasopressinase and safe in pregnancy.

Clinical features

Polyuria (often several litres a day, sometimes exceeding 10 litres in severe cases), polydipsia and nocturia are the cardinal features.⁵ Patients often describe an unusual craving for cold water. Urine is pale and dilute.

Differential diagnosis

The essential differential for polyuria and polydipsia is threefold, and distinguishing between them is the entire point of the investigation pathway.

Distinguishing diabetes insipidus, primary polydipsia and diabetes mellitus.
Condition	Mechanism	Key distinguishing feature
Cranial/nephrogenic DI	Failure of ADH secretion or action	Plasma osmolality high or high-normal; urine fails to concentrate on fluid deprivation
Primary (psychogenic) polydipsia	Excessive water intake driving physiological suppression of ADH	Plasma osmolality low-normal; urine does concentrate on fluid deprivation, without needing desmopressin
Diabetes mellitus	Osmotic diuresis from glycosuria	Glucose present in the urine; plasma glucose raised; a completely different mechanism, but can also present with polyuria and polydipsia

Investigations

Initial tests

Paired plasma and urine osmolality is the key first step. The combination of a high or high-normal plasma osmolality with an inappropriately dilute urine osmolality (relative to the plasma) strongly suggests DI, and if plasma osmolality is already high with dilute urine, a formal water deprivation test may not even be needed. Also check U&Es (sodium, calcium, potassium), glucose (to exclude diabetes mellitus) and a drug history, particularly lithium.²

Water deprivation test

Performed under close supervision when initial osmolalities are equivocal. Fluids are withheld, and plasma and urine osmolality are measured hourly along with weight, stopping if more than 3% of body weight is lost. Desmopressin is then given at the end of the test, and the response distinguishes the cause.

Interpreting the water deprivation test.
Diagnosis	Urine osmolality after fluid deprivation	Response to desmopressin
Normal	Concentrates appropriately (typically over 600 mosm/kg)	Little further change
Cranial DI	Remains inappropriately dilute	Urine concentrates significantly (classically by more than 50%) - ADH is deficient but the kidney can still respond
Nephrogenic DI	Remains inappropriately dilute	No significant concentration - the kidney cannot respond to ADH regardless of the source
Primary polydipsia	Concentrates on deprivation alone, without desmopressin (though the maximum achieved may be blunted by chronic medullary washout)	Little further change

Imaging

MRI pituitary is used for suspected cranial DI, looking for a structural cause and for loss of the normal posterior pituitary 'bright spot' on unenhanced T1-weighted imaging - a signal thought to reflect stored vasopressin, which is characteristically absent in cranial DI.³

Sagittal unenhanced T1-weighted MRI of the brain showing the pituitary gland, with the posterior pituitary appearing as a bright signal (arrow) and the anterior pituitary indicated separately (arrowhead). — Normal sagittal T1-weighted MRI showing the posterior pituitary 'bright spot' (arrow), thought to represent stored vasopressin. This bright spot is characteristically absent in cranial diabetes insipidus.Hellerhoff, CC BY-SA 3.0, via Wikimedia Commons

Management

Management by type.
Type	Management
Cranial DI	Desmopressin (DDAVP)⁴ - oral, intranasal or subcutaneous, titrated to symptoms, urine output and sodium. Also treat the underlying cause where identifiable (e.g. resect a tumour).
Nephrogenic DI	Treat/remove the cause - stop lithium if clinically possible (in discussion with psychiatry), correct hypercalcaemia or hypokalaemia. Thiazide diuretics paradoxically reduce urine volume by causing mild volume depletion, which increases proximal tubular water and sodium reabsorption. NSAIDs reduce renal prostaglandins, which normally antagonise ADH, and can further reduce urine volume. A low-salt, low-protein diet reduces the osmotic load that must be excreted.

Complications

Severe dehydration and hypernatraemia if fluid access is lost, which can cause confusion, seizures and death
Dilutional hyponatraemia from over-treatment with desmopressin
Hydronephrosis and a dilated, poorly contractile bladder from chronically high urine volumes in longstanding untreated disease
Sleep disruption from severe nocturia
Complications of the underlying cause - tumour, TBI, infiltrative disease

Red flags

Act on these

Polyuria with reduced consciousness, post-operative status, or in an infant - no reliable thirst response; ensure fluid replacement is prescribed rather than relying on the patient to drink
New polyuria in the days after pituitary surgery followed a week or so later by falling urine output - anticipate the triphasic response and monitor sodium closely rather than assuming DI has simply resolved
Confusion, seizures or a rapidly rising sodium in a patient with known DI - severe hypernatraemic dehydration; correct gradually to avoid cerebral oedema from over-rapid correction
A patient on desmopressin who becomes confused with normal or expanding fluid intake - consider dilutional hyponatraemia from over-treatment
Polyuria plus polydipsia with glycosuria - check plasma glucose; do not assume DI without excluding diabetes mellitus first

Prognosis

With adequate desmopressin replacement, patients with cranial DI can expect normal fluid balance, normal sodium and an essentially normal life, provided they have reliable access to water and medication. Nephrogenic DI caused by lithium may improve after stopping the drug, though recovery can be incomplete after long-term use, and DI from irreversible structural causes (e.g. destructive tumour, severe TBI) is usually permanent.

Pregnancy-related DI from placental vasopressinase resolves within weeks of delivery. The main determinant of long-term outcome is reliable access to water and medication, and patient education about sick day management and the risks of both under- and over-treatment with desmopressin.

References

NICE Clinical Knowledge Summaries. Diabetes insipidus. Available here
Society for Endocrinology. Clinical practice guidance - disorders of water balance. Available here
Di Iorgi N, Napoli F, Allegri AE et al. Diabetes insipidus - diagnosis and management. Hormone Research in Paediatrics. 2012. Available here
BNF. Desmopressin acetate. Available here
NHS. Diabetes insipidus. Available here
Hellerhoff, CC BY-SA 3.0, via Wikimedia Commons. Available here

This article is written for revision and education. It is not clinical guidance and must not be used to make decisions about the care of a patient. Always check current NICE guidance and local protocols.