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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Cranial DI: deficient ADH production (pituitary/hypothalamic damage — surgery, tumour, trauma, autoimmune, idiopathic)
- Nephrogenic DI: kidneys resistant to ADH (lithium is commonest drug cause; also: hypercalcaemia, hypokalaemia, CKD, genetic)
- Clinical: massive polyuria (3–20 L/day), polydipsia, nocturia. If access to water maintained → eunatraemic. If not → hypernatraemia, dehydration
- Diagnosis: paired serum and urine osmolality (serum high, urine inappropriately dilute). Water deprivation test ± desmopressin differentiates types
- Cranial DI: urine concentrates with desmopressin. Nephrogenic DI: urine does NOT concentrate with desmopressin
- Treatment: cranial DI → desmopressin (DDAVP). Nephrogenic DI → treat cause + thiazide diuretic (paradoxically reduces urine volume) + low-salt diet
Overview
Diabetes insipidus (DI) is characterised by the excretion of large volumes (>3 L/day in adults) of dilute urine, resulting from either inadequate secretion of antidiuretic hormone (ADH, vasopressin) from the posterior pituitary (cranial DI) or renal resistance to the action of ADH (nephrogenic DI). The term "arginine vasopressin deficiency" (AVP-D) for cranial DI and "arginine vasopressin resistance" (AVP-R) for nephrogenic DI has been proposed to avoid confusion with diabetes mellitus. Cranial causes include pituitary surgery, craniopharyngioma, trauma, sarcoidosis, histiocytosis, and autoimmune hypophysitis. Nephrogenic causes include lithium therapy (most common drug cause), hypercalcaemia, hypokalaemia, and inherited mutations (V2 receptor or aquaporin-2 genes).
Epidemiology
DI is uncommon, with a prevalence of approximately 1 in 25,000. Cranial DI is more common than nephrogenic. Post-neurosurgical DI (especially transsphenoidal pituitary surgery) is relatively common — transient DI occurs in up to 30% (usually resolves within days), permanent in ~5%. Lithium is the most common cause of drug-induced nephrogenic DI, affecting up to 40% of long-term lithium users to some degree. Primary polydipsia (psychogenic) is an important differential — must be excluded before diagnosing DI.
Clinical Features
Symptoms
Polyuria: large volumes of dilute urine (3–20 L/day), including nocturia
Polydipsia: intense thirst with craving for cold water
Nocturia disrupting sleep
Dehydration if water intake insufficient (especially post-operative, unconscious, or infant patients)
Symptoms of hypernatraemia if untreated: confusion, lethargy, irritability, seizures, coma
Signs
Dehydration (if water-deprived): dry mucous membranes, reduced skin turgor, tachycardia
Hypernatraemia if access to water is restricted
Signs of underlying cause: visual field defect (pituitary tumour), post-surgical
Investigations
First-line
Serum osmolalityHigh (>295 mOsm/kg) or high-normal
Urine osmolalityInappropriately low (<300 mOsm/kg, often <100) despite high serum osmolality. In DI, urine is dilute when it should be concentrated
Serum sodiumHigh or high-normal. Overt hypernatraemia (>145 mmol/L) if water intake insufficient
Urine volume24 h collection: >3 L/day confirms polyuria
Second-line
Water deprivation test (modified)Deprive water for 8 h (supervised, weigh regularly — stop if >5% weight loss). Measure urine osmolality. Then give desmopressin 2 mcg IM and recheck urine osmolality 2–4 h later
Interpretation of WDTCranial DI: urine dilute during deprivation → concentrates >600 after desmopressin. Nephrogenic DI: urine remains dilute (<300) even after desmopressin. Primary polydipsia: urine partially concentrates during deprivation (no ADH deficiency or resistance)
Specialist
Copeptin (AVP surrogate)Emerging test — copeptin is co-secreted with ADH. Low in cranial DI, normal/high in nephrogenic DI. May replace water deprivation test
MRI pituitaryIf cranial DI: assess for pituitary/hypothalamic pathology. Loss of posterior pituitary bright spot on T1 supports diagnosis
Anterior pituitary function testsCranial DI may be part of panhypopituitarism — assess cortisol, TFTs, gonadotrophins, IGF-1
Management
Endocrine Society; NICE CKS1
Cranial DI
- Desmopressin (DDAVP): synthetic ADH analogue. Intranasal (10–20 mcg), oral (100–400 mcg), or sublingual
- Titrate dose to control polyuria and thirst while avoiding hyponatraemia
- Monitor serum sodium regularly — risk of dilutional hyponatraemia if excessive desmopressin
- Teach patient: one "dry" period per week (allow breakthrough polyuria) to avoid water intoxication
- Treat underlying cause if identified (e.g. corticosteroids for sarcoidosis/histiocytosis)
2
Nephrogenic DI
- Remove/treat cause: stop lithium if possible (discuss with psychiatrist), correct hypercalcaemia, correct hypokalaemia
- Thiazide diuretic (e.g. bendroflumethiazide): paradoxically reduces urine volume by promoting proximal tubular reabsorption
- Low-sodium, low-protein diet (reduces solute load)
- Amiloride: particularly useful for lithium-induced NDI (blocks lithium entry into collecting duct cells)
- NSAIDs (indomethacin): can reduce urine volume (reduce prostaglandin-mediated antagonism of ADH)
- Ensure adequate fluid access at all times
Complications
- Hypernatraemia: If water intake restricted (post-operative, unconscious, infant) — can cause cerebral oedema if corrected too rapidly
- Dehydration: Particularly dangerous in elderly or immobile patients
- Hyponatraemia: From excessive desmopressin therapy (water intoxication)
- Sleep disruption: From severe nocturia
UKMLA Exam Tips
- 1DI = high serum osmolality + low urine osmolality (dilute urine when serum is concentrated). SIADH = the OPPOSITE
- 2Water deprivation test: cranial DI responds to desmopressin (urine concentrates). Nephrogenic does NOT respond
- 3Lithium = most common DRUG cause of nephrogenic DI. Also causes hypothyroidism and nephrotoxicity
- 4Post-neurosurgery polyuria: consider cranial DI — check Na⁺ and urine osmolality urgently
- 5Primary polydipsia: serum osmolality is LOW-normal (not high), urine partially concentrates on water deprivation
- 6Posterior pituitary bright spot absent on MRI T1 = supports cranial DI diagnosis
- 7Desmopressin for cranial DI — but monitor Na⁺ closely (risk of hyponatraemia from excess dosing)
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