STEPTRACKERENDOCRINE + RENAL | PATHOLOGY + PHYSIOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Posterior Pituitary & Water Balance

Too little ADH, too little response to it, or too much of it — sorted by serum sodium, urine osmolality and the water deprivation test.

FOCUS ON
Diabetes insipidus: polyuria of dilute urine with high-normal serum Na⁺. Central (no ADH) responds to desmopressin; nephrogenic (lithium, hypercalcemia, hypokalemia) doesn't — treat with thiazides/amiloride. SIADH: euvolemic hyponatremia with inappropriately concentrated urine (small cell lung cancer, CNS, drugs). Correct chronic hyponatremia slowly → avoid osmotic demyelination.
DISORDER
MECHANISM · CAUSE
FINDINGS
TREATMENT · CLUE
ADH physiology
Made in supraoptic and paraventricular nuclei; released from posterior pituitary; V2 receptor → cAMP → aquaporin-2 in collecting duct
Released when plasma osmolality rises or volume falls
V1 receptor → vasoconstriction
Central DI
↓ ADH: idiopathic, head trauma, pituitary surgery, tumors (craniopharyngioma, germinoma), LCH, sarcoid, hypoxic brain injury
Polyuria, polydipsia (likes ice water), urine osm < 300, serum Na⁺ high-normal/↑
Desmopressin → urine concentrates
Nephrogenic DI
Collecting duct resistance: lithium, demeclocycline, hypercalcemia, hypokalemia, X-linked AVPR2 or AQP2 mutations
Same picture; ADH level normal or ↑
No response to desmopressin · thiazides, amiloride (lithium), NSAIDs, low-salt diet
Primary polydipsia
Excess water intake (psychiatric illness)
Dilute urine but low serum Na⁺/osmolality
Urine concentrates with water deprivation
SIADH
ADH released without osmotic or volume stimulus → water retention → dilutional hyponatremia; natriuresis keeps volume normal
Euvolemic hyponatremia, serum osm low, urine osm > 100 (inappropriately concentrated), urine Na⁺ > 40, low uric acid
Fluid restriction, salt tablets, tolvaptan/conivaptan, demeclocycline
SIADH — causes
Ectopic or excess ADH
Small cell lung cancer, CNS (trauma, stroke, SAH, meningitis), lung disease (pneumonia, TB), drugs (SSRIs, carbamazepine, cyclophosphamide, vincristine), pain, nausea, surgery
Think small cell in a smoker
Severe symptomatic hyponatremia
Water moves into brain cells → cerebral edema
Headache, confusion, seizures, coma
Hypertonic (3%) saline in small boluses
Osmotic demyelination syndrome
Chronic hyponatremia corrected too fast (> 8–10 mEq/L/day) → oligodendrocyte injury, pons
Days later: dysarthria, dysphagia, quadriparesis, "locked-in"
"From low to high, your pons will die"
Hypovolemic hyponatremia
Volume loss → appropriate ADH release: diarrhea, vomiting, diuretics (thiazides), adrenal insufficiency, cerebral salt wasting (SAH)
Dry; urine Na⁺ low (GI) or high (renal, thiazide, Addison)
Isotonic saline
Hypervolemic hyponatremia
↓ effective circulating volume → ADH + RAAS
Edema: heart failure, cirrhosis, nephrotic syndrome; urine Na⁺ low
Fluid and salt restriction, diuretics
Low-solute hyponatremia
Too little solute to excrete free water: beer potomania, "tea and toast"
Very dilute urine (osm < 100)
Rapid overcorrection risk when solute given

Mechanism — ADH and the collecting duct

↑ Plasma osmolalityOsmoreceptors
→
HypothalamusSupraoptic nucleus
→
Posterior pituitaryADH released
→
V2 → cAMPAquaporin-2 inserted
→
Water reabsorbedConcentrated urine

Lithium enters principal cells through ENaC and blocks the V2 pathway — amiloride (ENaC blocker) keeps it out.

Water deprivation test

DIAGNOSIS
AFTER DEPRIVATION
AFTER DESMOPRESSIN
Normal
Urine osm rises
Little further change
Primary polydipsia
Urine osm rises
Little further change
Central DI
Stays dilute
Rises > 50%
Nephrogenic DI
Stays dilute
No change

How it's tested

COMMON CONFUSIONPrimary polydipsia and DI both cause polyuria of dilute urine. Low serum sodium points to polydipsia; high-normal sodium points to DI.
THE TRAPThiazides treat nephrogenic DI (volume contraction ↑ proximal reabsorption) yet cause hyponatremia in others. Same drug, opposite context.
YOUR APPROACHSerum Na⁺ and osm → volume status → urine osm and Na⁺ → cause (drug, tumor, CNS, lung) → correct at a safe rate.

If you see… think…

Polyuria after pituitary surgery, urine concentrates with desmopressin → central DI
Bipolar patient on lithium with polyuria, no response to desmopressin → nephrogenic DI — amiloride
Polyuria with serum Ca²⁺ 13 → hypercalcemia-induced nephrogenic DI
Schizophrenic with polyuria and Na⁺ 128 → primary polydipsia
Smoker with Na⁺ 122, euvolemic, urine osm 500 → SIADH (small cell lung cancer)
Hyponatremia after starting sertraline in an older woman → SSRI-induced SIADH
Seizing patient with Na⁺ 112 → hypertonic saline bolus
Quadriparesis and dysarthria 3 days after Na⁺ 110 → 128 → osmotic demyelination
SAH patient, hyponatremic and dehydrated, high urine Na⁺ → cerebral salt wasting
V2 receptor antagonist for SIADH → tolvaptan / conivaptan