🧪 Vasopressin (antidiuretic hormone, ADH; arginine vasopressin, AVP) is a nonapeptide synthesised in the hypothalamus and stored in the posterior pituitary. 💧 It is the key regulator of water reabsorption in the distal nephron. 📈 A rise in plasma osmolality of as little as 1% (threshold ~280–285 mOsm/kg H₂O) triggers AVP release → water retention + concentrated urine.

📖 About

Produced in the supraoptic & paraventricular nuclei of the hypothalamus, stored in the posterior pituitary.
Diabetes Insipidus (DI) = failure of AVP secretion or action → inability to concentrate urine → polyuria, polydipsia, hypernatraemia risk.
👉 Cranial DI: Impaired secretion.
👉 Nephrogenic DI: Kidneys unresponsive.
Severe DI: urine output can exceed 10–12 L/day.

⚙️ Physiology

AVP release is controlled by plasma osmolality & blood volume/pressure.
Acts via V2 receptors on collecting duct principal cells.
Activates cAMP–PKA pathway → insertion of aquaporin-2 channels.
Effect: ↑ water reabsorption, ↓ urine output, concentrated urine.

🧬 Aetiology

Loss of AVP action → uncontrolled free water loss.
If water intake inadequate → ⚠️ rapid dehydration & hypernatraemia.
Note: >80–90% hypothalamic neuron loss needed before symptoms appear.

🧠 Cranial (Central) DI – Causes

Idiopathic (most common in adults).
Trauma, neurosurgery, craniopharyngioma.
Sarcoidosis, TB, histiocytosis X.
Meningitis, encephalitis, subarachnoid haemorrhage.
Familial (rare, AD inheritance).
Syndromic (e.g. DIDMOAD: DI, DM, optic atrophy, deafness).

🧩 Nephrogenic DI – Causes

💊 Drugs: Lithium, demeclocycline.
⚡ Electrolytes: Hypercalcaemia, hypokalaemia.
CKD: Pyelonephritis, obstruction, amyloidosis, PKD.
Inherited mutations: V2 receptor or aquaporin-2 defects.
Systemic: Sickle cell disease, sarcoidosis.

📋 Clinical Features

💧 Polyuria: large volumes of dilute urine.
🚰 Polydipsia, intense thirst.
⚠️ Hypernatraemia if fluid intake inadequate → confusion, seizures, coma.
↑ VTE risk from haemoconcentration.

🔬 Investigations

🩺 Bloods: U&E (↑ Na⁺), ↑ plasma osmolality.
🧪 Urine: low osmolality despite high volume.
💡 Water deprivation test: confirms DI.
– Central DI: urine concentrates after desmopressin.
– Nephrogenic DI: no response to desmopressin.
Consider MRI brain (pituitary/hypothalamus).

🔎 Differential of Polyuria

Diabetes mellitus (osmotic diuresis).
Hypercalcaemia.
Diuretics.
Psychogenic polydipsia (excessive fluid intake).
CKD.
Post-obstructive diuresis.

💊 Management

Cranial DI: Desmopressin (DDAVP) – intranasal, oral, or injection. ⚠️ Monitor for hyponatraemia.
Nephrogenic DI: Low-salt diet, thiazides ± amiloride. NSAIDs (indomethacin) can ↓ urine output.
Lithium-induced DI: Amiloride (blocks lithium uptake in collecting duct). Stop lithium if possible.
General: Careful correction of hypernatraemia – avoid rapid shifts (risk of cerebral oedema).

📚 Teaching Pearls

💡 Exam buzzwords: Polyuria + hypernatraemia + low urine osmolality. 💡 Always distinguish from diabetes mellitus (check urine glucose). 💡 Water deprivation + desmopressin test = gold standard. 💡 In psychiatry patients with polydipsia, always consider psychogenic vs DI.

📚 References

Cases — Diabetes Insipidus (DI)

Case 1 — Central DI after Pituitary Surgery 🧠: A 45-year-old woman develops sudden-onset polyuria (8 L/day) and polydipsia following transsphenoidal surgery for a pituitary macroadenoma. Urine: very dilute (osmolality 80 mOsm/kg). Plasma sodium: 152 mmol/L. Diagnosis: Central diabetes insipidus (loss of ADH secretion). Management: Desmopressin (DDAVP); fluid replacement; monitor electrolytes closely.
Case 2 — Nephrogenic DI from Lithium 💊: A 60-year-old man with bipolar disorder on long-term lithium presents with excessive thirst and nocturia. Urine remains dilute despite rising serum osmolality. Water deprivation test: no response to desmopressin. Diagnosis: Nephrogenic diabetes insipidus secondary to lithium. Management: Stop lithium if possible; consider amiloride/thiazide + NSAIDs; low-salt, low-protein diet.
Case 3 — Primary Polydipsia Mimicking DI 🚰: A 30-year-old woman reports constant thirst and drinking >6 L/day. Exam: normal. Labs: low-normal plasma sodium, urine osmolality increases significantly with water deprivation test. Diagnosis: Psychogenic (dipsogenic) polydipsia, not true DI. Management: Behavioural modification, psychiatric input; avoid unnecessary desmopressin (risk of hyponatraemia).

Teaching Commentary 🧠

Diabetes insipidus = impaired water reabsorption due to ADH deficiency (central) or renal resistance (nephrogenic). - Central DI: trauma, surgery, pituitary tumour, idiopathic. - Nephrogenic DI: lithium, hypercalcaemia, hypokalaemia, inherited. - Dipsogenic: excessive fluid intake mimics DI. Dx: Water deprivation test → central DI responds to desmopressin, nephrogenic does not, primary polydipsia concentrates with deprivation alone. Mx: Desmopressin for central; remove offending drugs + thiazides/amiloride for nephrogenic; behavioural therapy for dipsogenic.

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Diabetes Insipidus (AVP Deficiency)