A 65-year-old man on long-term lithium therapy presents with polyuria (6 litres/day) and polydipsia. Serum sodium 148 mmol/L, serum osmolality 310 mosm/kg, urine osmolality 140 mosm/kg, urine sodium 20 mmol/L. Water deprivation test: urine osmolality increases to only 165 mosm/kg. After desmopressin injection: urine osmolality 175 mosm/kg (increase <10%). This pattern is consistent with:
- A Central diabetes insipidus (CDI)
- B Primary polydipsia (psychogenic polydipsia)
- C Nephrogenic diabetes insipidus (NDI) caused by lithium-induced downregulation of AQP2 ✓
- D Osmotic diuresis from uncontrolled diabetes mellitus
Explanation
Lithium causes nephrogenic diabetes insipidus (NDI) by inhibiting adenylate cyclase in collecting duct principal cells, reducing cAMP generation in response to ADH, and directly downregulating aquaporin-2 (AQP2) water channel expression. In NDI, the kidney is unresponsive to ADH; therefore, urine does not concentrate with water deprivation or after exogenous desmopressin (DDAVP) — response is <50% increase or absolute urine osmolality remains dilute. In CDI, desmopressin causes a marked increase (>50%) in urine osmolality. Primary polydipsia shows urine osmolality >300 after water deprivation. Osmotic diuresis would have elevated urine glucose/sodium.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.