💧 Diabetes Insipidus (DI) is a disorder of water balance caused by impaired vasopressin (ADH) secretion or renal response to ADH.
It results in inability to concentrate urine → polyuria, polydipsia, and risk of hypernatraemia.
🧠 Pathophysiology
- ADH (vasopressin) is synthesised in the supraoptic & paraventricular nuclei of the hypothalamus.
- Stored and released from the posterior pituitary.
- Acts on V2 receptors in collecting duct principal cells.
- Activates cAMP → PKA pathway → insertion of aquaporin-2 channels.
- Effect: ↑ water reabsorption, ↓ urine output, concentrated urine.
- In DI: failure of this pathway → excessive free water loss.
📂 Classification
- 🧠 Central (Cranial) DI – reduced ADH secretion.
- 🧩 Nephrogenic DI – renal resistance to ADH.
- 🚰 Primary (Dipsogenic) Polydipsia – excessive fluid intake suppresses ADH.
- 🤰 Gestational DI – pregnancy-related excess vasopressinase.
🧠 Central DI – Causes
- Idiopathic (commonest in adults)
- Post-pituitary surgery
- Head trauma
- Craniopharyngioma
- Sarcoidosis, TB, Langerhans cell histiocytosis
- Meningitis, SAH
- Familial (rare, AD inheritance)
🧩 Nephrogenic DI – Causes
- 💊 Lithium (commonest acquired cause)
- Demeclocycline
- Hypercalcaemia
- Hypokalaemia
- CKD, obstructive uropathy
- Inherited V2 receptor or aquaporin-2 mutations
- Sickle cell disease
🤰 Gestational DI
- Occurs in late pregnancy.
- Placenta produces vasopressinase which degrades ADH.
- More common in multiple pregnancy & pre-eclampsia.
- Resolves postpartum.
- Treated with desmopressin (resistant to vasopressinase).
📋 Clinical Features
- 💧 Polyuria (>3 L/day; severe cases >10–12 L/day)
- 🚰 Polydipsia
- Nocturia
- ⚠️ Hypernatraemia if water intake insufficient
- Neurological signs if severe: confusion, seizures, coma
🔬 Investigations
- ↑ Plasma osmolality
- ↑ Serum sodium
- Low urine osmolality (<300 mOsm/kg)
- Water deprivation test:
- Central DI → urine concentrates after desmopressin
- Nephrogenic DI → no response
- Primary polydipsia → concentrates with deprivation alone
- MRI pituitary if central cause suspected
💊 Management
- Central DI: Desmopressin (oral/intranasal). Monitor sodium.
- Nephrogenic DI: Treat cause; low-salt diet; thiazide ± amiloride; NSAIDs (indomethacin).
- Lithium-induced: Stop lithium if possible; amiloride preferred.
- Gestational DI: Desmopressin; resolves postpartum.
- Severe hypernatraemia: Correct slowly (≤10 mmol/L per 24h).
🧠 High-Yield Exam Points
💡 Polyuria + hypernatraemia + low urine osmolality = think DI.
💡 Always exclude diabetes mellitus first (check glucose).
💡 Desmopressin response distinguishes central from nephrogenic.
💡 Lithium is the commonest acquired nephrogenic cause.
💡 Gestational DI = vasopressinase excess in pregnancy.
