A 55-year-old man on lithium therapy for bipolar disorder for 12 years reports polyuria of 7 litres per day and polydipsia. After a supervised water deprivation test, urine osmolality rises only to 190 mOsm/kg. Desmopressin is administered subcutaneously, and urine osmolality remains below 220 mOsm/kg. Serum sodium is 144 mEq/L. What is the mechanism of his condition?
- A Downregulation of the thiazide-sensitive cotransporter causing impaired medullary tonicity
- B Destruction of magnocellular neurons of the supraoptic and paraventricular nuclei
- C Osmotic diuresis from lithium induced glycosuria
- D Impaired renal responsiveness to vasopressin due to reduced aquaporin-2 expression in the collecting duct ✓
Explanation
Chronic lithium accumulates in collecting duct principal cells and impairs vasopressin signalling by reducing aquaporin-2 synthesis and apical trafficking, producing nephrogenic diabetes insipidus. The diagnostic signature is failure of urine osmolality to rise by more than 50 percent after desmopressin during a water deprivation test, exactly as seen here. Central diabetes insipidus would respond briskly to desmopressin, and glycosuria would show glucose positivity on urinalysis, which is absent. Thiazides are actually used paradoxically to reduce urine volume in this condition.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.