ADH deficiency (central) or renal resistance (nephrogenic) causing dilute polyuria and hypernatremia if water access limited.
Also known as: diabetes insipidus, DI, central DI, nephrogenic DI, AVP deficiency, AVP resistance
Overview
Disorder of water balance defined by hypotonic polyuria due to either deficient secretion of arginine vasopressin (central DI, also called AVP deficiency) or renal resistance to AVP (nephrogenic DI, AVP resistance). Recent guidelines favor these descriptive names over 'diabetes insipidus' to prevent confusion with diabetes mellitus.
Epidemiology
Uncommon overall. Central DI more common than nephrogenic. Post-neurosurgical or traumatic CDI is the most common form encountered in hospitals. Lithium-induced nephrogenic DI is the most common drug cause. Congenital nephrogenic DI is rare and usually X-linked (AVPR2 mutation).
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Question 1EndocrineMedium
A 42-year-old woman is seen on postoperative day 3 after transsphenoidal resection of a pituitary macroadenoma. Over the past 24 hours she has had relentless thirst with a craving for ice water and has voided 6.5 L of urine. Vital signs show heart rate 104/min and blood pressure 102/64 mm Hg. Serum sodium is 149 mEq/L, serum osmolality is 304 mOsm/kg, and urine osmolality is 110 mOsm/kg. Serum glucose and calcium are normal. Which of the following is the most likely diagnosis?
AGlucose-driven osmotic diuresis
BAcute central diabetes insipidus
CNephrogenic diabetes insipidus
DCompulsive psychogenic polydipsia
Reveal answer & full explanation
Correct answer: B — Acute central diabetes insipidus
AGlucose-driven osmotic diuresis
BAcute central diabetes insipidus✓
CNephrogenic diabetes insipidus
DCompulsive psychogenic polydipsia
Why Acute central diabetes insipidus is correct
Sudden, massive hypotonic polyuria (greater than 5 L/day) appearing days after pituitary/hypothalamic surgery is central DI (AVP deficiency) until proven otherwise — the surgery disrupts AVP-producing neurons and the pituitary stalk.
The labs confirm true DI: dilute urine (osm 110 mOsm/kg) that is inappropriately lower than the serum osmolality (304 mOsm/kg) despite a rising serum sodium (149 mEq/L), meaning the kidney cannot concentrate urine in the face of free-water loss.
Craving for ice water is a classic central DI feature; treatment is desmopressin, a V2-selective AVP analog.
Why the others are wrong
Nephrogenic diabetes insipidus — renal resistance to AVP also gives dilute polyuria, but it points to a renal/drug cause (lithium, hypercalcemia, hypokalemia); here the abrupt onset right after pituitary surgery, with normal calcium, points to a central rather than renal cause.
Glucose-driven osmotic diuresis — glucosuria pulls water into the urine, but the urine is NOT dilute and serum glucose would be high; this patient has normal glucose and very dilute urine (osm 110 mOsm/kg).
Compulsive psychogenic polydipsia — excessive water intake drives polyuria, but AVP is appropriately suppressed and the patient is water-loaded, so serum sodium and osmolality run low-normal, not elevated (Na 149, osm 304) as seen here.
Question 2EndocrineMedium
A 34-year-old man reports 3 weeks of excessive thirst and urinating roughly 6 L per day, including waking several times nightly. He takes no medications and has no psychiatric history. Serum sodium is 147 mEq/L, glucose 92 mg/dL, and calcium 9.4 mg/dL. A supervised water deprivation test is performed: urine osmolality plateaus at 220 mOsm/kg while serum sodium rises to 150 mEq/L, and after subcutaneous desmopressin the urine osmolality increases to 610 mOsm/kg. Which of the following diagnoses do these findings best support?
ANephrogenic diabetes insipidus
BOsmotic diuresis from glucosuria
CPrimary psychogenic polydipsia
DCentral type diabetes insipidus
Reveal answer & full explanation
Correct answer: D — Central type diabetes insipidus
ANephrogenic diabetes insipidus
BOsmotic diuresis from glucosuria
CPrimary psychogenic polydipsia
DCentral type diabetes insipidus✓
Why Central type diabetes insipidus is correct
During water deprivation the urine stays inappropriately dilute (220 mOsm/kg) despite a rising serum sodium of 150 mEq/L, so the kidney cannot concentrate on its own.
After desmopressin (a V2-selective AVP analog) the urine osmolality rises by far more than 50% (220 to 610 mOsm/kg), meaning the collecting duct responds normally once exogenous AVP is supplied; the defect is deficient AVP secretion, the hallmark of central DI.
The high-normal baseline sodium (147 mEq/L) with hypotonic polyuria and normal glucose and calcium fits true DI rather than a mimic.
Why the others are wrong
Nephrogenic diabetes insipidus also fails to concentrate during deprivation, but urine shows minimal or no rise after desmopressin because the kidney resists AVP; a greater than 50% increase argues against it.
Primary psychogenic polydipsia retains AVP responsiveness, so urine concentrates above 600 mOsm/kg with deprivation alone and changes little after desmopressin; here the urine stayed dilute during deprivation.
Osmotic diuresis from glucosuria produces high-solute, non-dilute urine and requires hyperglycemia and glucosuria; this patient has a normal glucose of 92 mg/dL.
Per Endocrine Society guidance, the water-deprivation-plus-desmopressin pattern (or hypertonic saline-stimulated copeptin testing) distinguishes DI subtypes, and pituitary MRI to evaluate for a stalk or hypothalamic lesion is the appropriate next step once central DI is confirmed.
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Gestational DI: placental vasopressinase degradation of AVP (responds to desmopressin)
Primary polydipsia (compulsive water intake or low set-point) — not true DI but mimics it
Pathophysiology
AVP is synthesized in the supraoptic and paraventricular nuclei, transported down the pituitary stalk, and stored in the posterior pituitary. Plasma osmolality is sensed by hypothalamic osmoreceptors; AVP release increases water reabsorption in collecting ducts via V2 receptors and aquaporin-2. Loss of AVP secretion or V2 receptor/AQP2 function produces dilute polyuria. As long as thirst is intact and water access is unrestricted, serum sodium remains near normal; if not, severe hypernatremia develops.
Clinical presentation
Symptoms
Polyuria (often >3 L/day, can be much more), nocturia, polydipsia
Preference for ice water (classic in CDI)
Fatigue, weakness, irritability
Severe cases: confusion, lethargy, seizure (hypernatremia)
Signs / physical exam
Dehydration if access to water restricted
Hypotension, tachycardia (volume depletion)
Altered mental status with severe hypernatremia
Children: failure to thrive, fever, irritability
Classic findings
Adult with sudden onset of severe polyuria (>5 L/day) and polydipsia after pituitary surgery — CDI until proven otherwise. Lithium user with polyuria — nephrogenic DI.
Differential diagnosis
Primary polydipsia (psychogenic, dipsogenic) — Polydipsia drives polyuria; suppressed AVP appropriately; water deprivation test shows ability to concentrate urine (>600 mOsm/kg)
Resolving acute kidney injury (polyuric phase) — Self-limited; supportive care
Diagnostic workup
Diagnostic criteria
Polyuria + dilute urine (osm < serum osm) + appropriate response (or lack thereof) to water deprivation and DDAVP.
Labs
Simultaneous serum and urine osmolality
Serum Na (often high-normal or elevated in true DI; normal/low in primary polydipsia)
Plasma copeptin (a stable surrogate for AVP) — emerging tool to differentiate DI subtypes
BMP, calcium, glucose (rule out mimics)
Lithium level if applicable
24-hour urine volume to confirm polyuria (>3 L/day or >50 mL/kg/day)
Imaging
Pituitary MRI for suspected central DI — look for absence of posterior pituitary 'bright spot,' pituitary stalk thickening, mass, or infiltration
Renal ultrasound if obstructive uropathy or other renal pathology suspected
Diagnostic algorithm
Test
Central DI
Nephrogenic DI
Primary polydipsia
Baseline serum Na
High-normal / high
High-normal / high
Low-normal / low
Baseline urine osm
Low (<300)
Low (<300)
Low (<300)
After water deprivation, urine osm
Remains low
Remains low
Rises >600
After DDAVP, urine osm
Rises >50%
Minimal rise (<10-50%)
No further rise
Copeptin (basal or hypertonic-stim)
Low
High
Normal / appropriate
MRI posterior pituitary bright spot
Absent
Present
Present
Differentiating central DI, nephrogenic DI, and primary polydipsia.
Complications
Severe hypernatremia → altered mentation, seizure, intracranial bleed, death
Hypovolemic shock
Cerebral edema from too-rapid correction of hypernatremia
Hyponatremia from desmopressin over-treatment
Bladder atony from chronic polyuria
Failure to thrive in infants with congenital NDI
PANCE pearls
Pituitary surgery causes a classic 'triphasic response': polyuria (1st week) → SIADH (transient inappropriate retention, ~days 5-10) → permanent DI (or recovery). Watch for hyponatremia between phases.
Lithium is the most common acquired cause of nephrogenic DI; can persist after lithium discontinuation.
Primary polydipsia and DI BOTH cause polyuria — water deprivation test or copeptin testing distinguishes.
Hypernatremia correction must be SLOW (≤10-12 mEq/L per 24 h) to prevent cerebral edema.
Thiazides treat nephrogenic DI by paradoxically reducing urine volume (volume contraction enhances proximal sodium and water reabsorption).
After pituitary surgery, daily Na and ins/outs are essential for the first 7-10 days.
References
Working Group 2022 — Renaming of Diabetes Insipidus to AVP-Deficiency and AVP-Resistance (Working Group on Renaming Diabetes Insipidus, J Clin Endocrinol Metab 2022)
European Consensus 2022 — Diagnosis and Management of Central Diabetes Insipidus in Adults (Garrahy et al., J Clin Endocrinol Metab 2022)
Endocrine Society — Posterior pituitary disorders guidelines — multiple statements on hyponatremia and hypernatremia management
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