A patient on lithium therapy for bipolar disorder develops polyuria of 6 litres/day with dilute urine (osmolality 120 mOsm/kg). Urine osmolality does not rise after intranasal desmopressin. This presentation is consistent with:
- A Central diabetes insipidus from lithium-induced hypothalamic toxicity
- B Psychogenic polydipsia with urinary concentration failure
- C Nephrogenic diabetes insipidus (NDI) due to lithium-induced aquaporin-2 downregulation ✓
- D Medullary washout from primary polydipsia
Correct answer: C. Nephrogenic diabetes insipidus (NDI) due to lithium-induced aquaporin-2 downregulation
Explanation
Lithium induces nephrogenic DI by impairing renal collecting duct response to ADH — specifically by downregulating aquaporin-2 (AQP2) water channels via inhibition of glycogen synthase kinase-3β (GSK-3β) — blunting cAMP-mediated AQP2 trafficking. The failure of desmopressin to raise urine osmolality confirms renal (nephrogenic) resistance to ADH, not central deficiency. Central DI would respond to desmopressin. Psychogenic polydipsia does respond to desmopressin but urine osmolality is >300 initially.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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