A 22-year-old man reports polyuria of 8 liters per day and polydipsia. During a supervised water deprivation test, urine osmolality fails to rise above 150 mOsm/kg despite a plasma osmolality of 305 mOsm/kg. After subcutaneous desmopressin, urine osmolality rises to 520 mOsm/kg. What is the underlying defect?
- A Destruction of ADH-producing magnocellular neurons of the supraoptic and paraventricular nuclei ✓
- B Mutation of the vasopressin V2 receptor on renal collecting duct cells
- C Loss of aquaporin-2 expression due to chronic lithium exposure
- D Osmoreceptor failure resetting the threshold for ADH release
Correct answer: A. Destruction of ADH-producing magnocellular neurons of the supraoptic and paraventricular nuclei
Explanation
Inability to concentrate urine after dehydration with a prompt rise in urine osmolality after desmopressin defines central diabetes insipidus, caused by deficient ADH synthesis or release from the hypothalamic magnocellular neurons. Nephrogenic diabetes insipidus, whether from V2 receptor mutation or lithium-induced aquaporin-2 downregulation, shows no osmotic response to exogenous desmopressin, which kills options B and C.
Reference: Ganong's Review of Medical Physiology, 26th ed.
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