💧 Diabetes Insipidus (DI), now often termed arginine vasopressin deficiency or arginine vasopressin resistance, is a disorder of water balance caused by impaired vasopressin/ADH secretion or impaired renal response to vasopressin.
It causes inability to concentrate urine → polyuria, polydipsia, nocturia and risk of dehydration/hypernatraemia.
🧠 Pathophysiology
- ADH/vasopressin is synthesised in the supraoptic and paraventricular nuclei of the hypothalamus.
- It is stored and released from the posterior pituitary.
- It acts on V2 receptors in collecting duct principal cells.
- This activates the cAMP → PKA pathway → insertion of aquaporin-2 water channels.
- Normal effect: ↑ water reabsorption, ↓ urine output and concentrated urine.
- In DI, failure of this pathway causes excessive free-water loss and dilute urine.
📂 Classification
- 🧠 Central/Cranial DI — reduced vasopressin secretion; also called arginine vasopressin deficiency.
- 🧩 Nephrogenic DI — renal resistance to vasopressin; also called arginine vasopressin resistance.
- 🚰 Primary/dipsogenic polydipsia — excessive fluid intake suppresses vasopressin and lowers plasma osmolality.
- 🤰 Gestational DI — pregnancy-related excess vasopressinase causing increased vasopressin breakdown.
🧠 Central DI — Causes
- Post-pituitary or hypothalamic surgery
- Head trauma
- Pituitary/hypothalamic tumours, including craniopharyngioma and metastases
- Idiopathic or autoimmune
- Infiltrative/inflammatory disease: sarcoidosis, TB, Langerhans cell histiocytosis
- CNS infection, meningitis or subarachnoid haemorrhage
- Familial causes, rarely autosomal dominant
🧩 Nephrogenic DI — Causes
- 💊 Lithium — common acquired cause
- Demeclocycline
- Hypercalcaemia
- Hypokalaemia
- CKD or obstructive uropathy
- Inherited V2 receptor or aquaporin-2 mutations
- Sickle cell disease
🤰 Gestational DI
- Usually occurs in late pregnancy.
- The placenta produces vasopressinase, which degrades endogenous vasopressin.
- Risk is increased in multiple pregnancy, pre-eclampsia and liver dysfunction.
- Usually resolves postpartum.
- Treated with desmopressin, which is resistant to vasopressinase.
📋 Clinical Features
- 💧 Polyuria: usually >3 L/day in adults; severe cases may exceed 10 L/day.
- 🚰 Polydipsia and preference for cold drinks.
- 🌙 Nocturia and sleep disturbance.
- ⚠️ Hypernatraemia and dehydration if water intake is inadequate.
- 🧠 Severe hypernatraemia may cause confusion, seizures, reduced consciousness or coma.
🔬 Investigations
- Exclude common mimics first: check capillary/serum glucose, U&E, calcium, potassium, renal function and medication history.
- Confirm hypotonic polyuria: 24-hour urine volume if needed, paired serum and urine osmolality, and serum sodium.
- Typical DI pattern: high or high-normal plasma osmolality, high or high-normal sodium, and inappropriately dilute urine, often urine osmolality <300 mOsm/kg.
- Water deprivation test: specialist/supervised test only. It assesses whether urine concentrates during dehydration and then after desmopressin.
- Interpretation:
- Central DI: urine remains dilute during deprivation but concentrates after desmopressin.
- Nephrogenic DI: urine remains dilute and shows little/no response to desmopressin.
- Primary polydipsia: urine concentrates with deprivation alone.
- Copeptin testing may be used in specialist centres to help distinguish DI from primary polydipsia.
- MRI pituitary/hypothalamus if central DI is suspected.
💊 Management of Diabetes Insipidus
- 🚰 General principles:
Ensure free access to water if conscious, alert and able to drink. Monitor fluid balance, urine output, daily weight, serum sodium and plasma/urine osmolality where appropriate. Assess for dehydration, hypernatraemia, AKI, reduced consciousness and inability to self-administer desmopressin. Monitor abnormal sodium closely, especially in hospital or if IV fluids are being given. Avoid rapid sodium shifts.
- 🧠 Central DI / Arginine Vasopressin Deficiency:
Treat with desmopressin, titrated to thirst, urine output and serum sodium.
- Oral/sublingual desmopressin: 100–200 micrograms, usually once to three times daily.
- Intranasal desmopressin: 10–20 micrograms daily, sometimes in divided doses.
- IV/IM/SC desmopressin: 1–2 micrograms if acutely unwell, unable to take oral/nasal treatment, peri-operative or severely hypernatraemic.
- 🚨 Unwell inpatient with known central DI:
Treat as high-risk: do not omit or delay established desmopressin. If unable to drink, vomiting, nil by mouth, reduced consciousness or hypernatraemic, give appropriate IV fluid replacement with senior endocrine/medical advice. Use strict fluid balance and frequent serum sodium monitoring; during active resuscitation, sodium may need checking every 4 hours. Fluid replacement takes priority if clinically dehydrated, but avoid rapid overcorrection once desmopressin is given.
- 🧂 Nephrogenic DI / Arginine Vasopressin Resistance:
Desmopressin is usually ineffective because the kidney is resistant to vasopressin. Treat the cause: hypercalcaemia, hypokalaemia, renal disease, obstructive uropathy or drugs such as lithium. Ensure adequate water intake and consider a low-salt/low-solute diet. Consider thiazide diuretic ± amiloride to reduce polyuria. NSAIDs such as indomethacin may reduce urine output but should be used cautiously because of renal, GI and cardiovascular toxicity.
- 💊 Lithium-induced nephrogenic DI:
Stop or reduce lithium if possible, but only after psychiatric advice and risk assessment. Amiloride is preferred because it reduces lithium entry into collecting duct cells. Monitor lithium level, renal function, sodium and volume status.
- 🤰 Gestational DI:
Treat with desmopressin; it is resistant to placental vasopressinase and is usually effective. It usually resolves postpartum, but monitor sodium and fluid balance.
- ⚠️ Severe hypernatraemia:
Assess volume status and replace intravascular volume first if shocked or severely dehydrated. Correct gradually, usually aiming for a fall in serum sodium of no more than about 10 mmol/L per 24 hours. Use senior endocrine, renal or critical care advice if severe, acute, symptomatic or associated with impaired consciousness.
🧠 High-Yield Exam Points
💡 Polyuria + hypernatraemia/high plasma osmolality + low urine osmolality = think DI.
💡 Always exclude diabetes mellitus first: check glucose.
💡 Desmopressin response helps distinguish central from nephrogenic DI.
💡 Lithium is a common acquired cause of nephrogenic DI.
💡 Gestational DI = vasopressinase excess in pregnancy and responds to desmopressin.
💡 In hospital, omission of established desmopressin in cranial DI can be dangerous.
