π§ͺ Vasopressin (antidiuretic hormone, ADH; arginine vasopressin, AVP) is a nonapeptide synthesised in the hypothalamus and stored in the posterior pituitary.
π§ It is the key regulator of water reabsorption in the distal nephron.
π A rise in plasma osmolality of as little as 1% (threshold ~280β285 mOsm/kg HβO) triggers AVP release β water retention + concentrated urine.
π About
- Produced in the supraoptic & paraventricular nuclei of the hypothalamus, stored in the posterior pituitary.
- Diabetes Insipidus (DI) = failure of AVP secretion or action β inability to concentrate urine β polyuria, polydipsia, hypernatraemia risk.
- π Cranial DI: Impaired secretion.
π Nephrogenic DI: Kidneys unresponsive.
- Severe DI: urine output can exceed 10β12 L/day.
βοΈ Physiology
- AVP release is controlled by plasma osmolality & blood volume/pressure.
- Acts via V2 receptors on collecting duct principal cells.
- Activates cAMPβPKA pathway β insertion of aquaporin-2 channels.
- Effect: β water reabsorption, β urine output, concentrated urine.
𧬠Aetiology
- Loss of AVP action β uncontrolled free water loss.
- If water intake inadequate β β οΈ rapid dehydration & hypernatraemia.
- Note: >80β90% hypothalamic neuron loss needed before symptoms appear.
π§ Cranial (Central) DI β 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).
π§© Nephrogenic DI β Causes
- π Drugs: Lithium, demeclocycline.
- β‘ Electrolytes: Hypercalcaemia, hypokalaemia.
- CKD: Pyelonephritis, obstruction, amyloidosis, PKD.
- Inherited mutations: V2 receptor or aquaporin-2 defects.
- Systemic: Sickle cell disease, sarcoidosis.
π Clinical Features
- π§ Polyuria: large volumes of dilute urine.
- π° Polydipsia, intense thirst.
- β οΈ Hypernatraemia if fluid intake inadequate β confusion, seizures, coma.
- β VTE risk from haemoconcentration.
π¬ Investigations
- π©Ί Bloods: U&E (β NaβΊ), β plasma osmolality.
- π§ͺ Urine: low osmolality despite high volume.
- π‘ Water deprivation test: confirms DI.
β Central DI: urine concentrates after desmopressin.
β Nephrogenic DI: no response to desmopressin.
- Consider MRI brain (pituitary/hypothalamus).
π Differential of Polyuria
- Diabetes mellitus (osmotic diuresis).
- Hypercalcaemia.
- Diuretics.
- Psychogenic polydipsia (excessive fluid intake).
- CKD.
- Post-obstructive diuresis.
π Management
- Cranial DI: Desmopressin (DDAVP) β intranasal, oral, or injection. β οΈ Monitor for hyponatraemia.
- Nephrogenic DI: Low-salt diet, thiazides Β± amiloride. NSAIDs (indomethacin) can β urine output.
- Lithium-induced DI: Amiloride (blocks lithium uptake in collecting duct). Stop lithium if possible.
- General: Careful correction of hypernatraemia β avoid rapid shifts (risk of cerebral oedema).
π Teaching Pearls
π‘ Exam buzzwords: Polyuria + hypernatraemia + low urine osmolality.
π‘ Always distinguish from diabetes mellitus (check urine glucose).
π‘ Water deprivation + desmopressin test = gold standard.
π‘ In psychiatry patients with polydipsia, always consider psychogenic vs DI.
π References
Cases β Diabetes Insipidus (DI)
- Case 1 β Central DI after Pituitary Surgery π§ :
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 β Nephrogenic DI from Lithium π:
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 β Primary Polydipsia Mimicking DI π°:
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 π§
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 β 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.