Diabetes insipidus (central and nephrogenic) !
Diabetes insipidus causes large amounts of dilute urine and intense thirst, from a lack of the water-saving hormone or kidney resistance to it.
Updated 2026-11-01
Structures involved
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In embryology
Why it happens
- The posterior pituitary: ADH and oxytocin
- ADH, thirst and water balance
- The countercurrent mechanism, urea recycling and urine concentration
- Urine dilution, free water and osmotic diuresis
- Pituitary: adenohypophysis and neurohypophysis
What it is
A disorder of water balance in which the kidneys cannot concentrate urine, because of deficient secretion of vasopressin (antidiuretic hormone) or kidney resistance to it. New names are arginine vasopressin deficiency (central) and resistance (nephrogenic). It is unrelated to diabetes mellitus.
Who gets it
Rare. Central forms follow head injury, neurosurgery or pituitary and hypothalamic lesions; nephrogenic forms are most often acquired, from lithium, hypercalcaemia or hypokalaemia.
Causes
- Central: idiopathic or autoimmune, neurosurgery or traumatic brain injury
- Central: tumours (craniopharyngioma, metastases), infiltrative diseases (Langerhans cell histiocytosis, sarcoidosis), infection
- Nephrogenic: lithium, hypercalcaemia, hypokalaemia, chronic kidney disease
- Nephrogenic: inherited mutations of the vasopressin V2 receptor or aquaporin-2
- Gestational: placental breakdown of vasopressin
Risk factors
- Pituitary or hypothalamic surgery and head trauma
- Long-term lithium therapy
- Pituitary or sellar tumours
- Family history of nephrogenic diabetes insipidus
Pathophysiology
Vasopressin is made in the hypothalamus, stored in the posterior pituitary and acts on V2 receptors in the collecting duct to insert aquaporin-2 water channels. Without the hormone or without a kidney response, water is not reabsorbed and large volumes of dilute urine are lost. Thirst keeps sodium near normal; if access to water is limited, hypernatraemia develops.
Classification
- Central (arginine vasopressin deficiency)
- Nephrogenic (arginine vasopressin resistance)
- Gestational
- Complete or partial
Symptoms and signs
- Polyuria with large volumes of dilute urine, usually more than 3 litres a day in adults
- Intense thirst, with a preference for cold water
- Nocturia and disturbed sleep
- In infants: irritability, poor feeding, fever and poor growth
Diagnosis
- Clinical
- Confirm true polyuria with a 24-hour urine volume, then exclude hyperglycaemia, hypercalcaemia and hypokalaemia, and separate it from primary polydipsia.
- Tests
- Low urine osmolality with high-normal or high serum sodium and osmolality. Water deprivation test followed by desmopressin: urine concentrates after desmopressin in central disease and not in nephrogenic. Plasma copeptin (basal in nephrogenic, after stimulation for central versus primary polydipsia) is increasingly used.
- Imaging
- Pituitary and hypothalamic MRI in central forms: the posterior pituitary bright spot is usually lost; look for thickened stalk or tumour.
Differential diagnosis
- Primary (psychogenic) polydipsia
- Diabetes mellitus with osmotic diuresis
- Hypercalcaemia
- Post-obstructive or recovery-phase diuresis
- Diuretic use
Goal of treatment
Reduce urine output and thirst to tolerable levels, keep serum sodium normal, and treat the underlying cause.
Treatment
- Medical
- Central: desmopressin, a synthetic vasopressin analogue (oral, nasal or injected), adjusted to avoid hyponatraemia.
- Medical
- Nephrogenic: treat the cause (stop lithium if possible, correct calcium and potassium), thiazide diuretics, and sometimes amiloride for lithium-related disease or NSAIDs.
- Lifestyle
- Free access to water and, in nephrogenic forms, a low-salt, moderate-protein diet to reduce urine volume.
- Follow-up
- Strict intake and output, daily weight, urine specific gravity and serum sodium; nursing priority after neurosurgery is early detection of sudden polyuria.
- Surgical
- Surgery or radiotherapy for a causative sellar or hypothalamic tumour.
Complications
- Hypernatraemic dehydration with seizures or brain injury
- Hyponatraemia from excessive desmopressin
- Bladder distension and hydronephrosis in long-standing high urine volumes
- Growth failure in children
Prognosis
With access to water and treatment, most people live normally. Prognosis depends on the cause; transient central forms after surgery may resolve.
Test yourself
Think of the answer, then tap the question to see it.
How does the desmopressin test separate central from nephrogenic diabetes insipidus?
After water deprivation, urine osmolality rises clearly after desmopressin in central DI and changes little in nephrogenic DI.
Which drug is the classic cause of acquired nephrogenic diabetes insipidus?
Lithium.
What is the typical urine and serum pattern in diabetes insipidus?
Dilute urine (low osmolality and specific gravity) with high-normal or high serum sodium and osmolality.
What is the triple-phase response after pituitary surgery?
Initial DI, then a phase of inappropriate ADH release (SIADH) with hyponatraemia, then permanent DI.
Related conditions
- Pituitary adenoma
- Traumatic brain injury
- Primary hyperparathyroidism
- Chronic kidney disease
- Type 2 diabetes mellitus
- Type 1 diabetes mellitus
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Diabetes insipidus (MedlinePlus Medical Encyclopedia (U.S. National Library of Medicine), 2025).
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