Snapshot A 45-year-old woman presents to her primary care physician for persistent thirst. She has a past medical history of bipolar disorder and hypertension. She reports that the thirst began 4 weeks ago, along with increased trips to the bathroom. Her young cousin was recently diagnosed with diabetes after similar symptoms, and she is worried that she has diabetes. On physical exam, she has dry mucous membranes. A closer look at her medication list shows a new medication, lithium, started about 8 weeks ago. (Nephrogenic diabetes insipidus) Introduction Clinical definition diabetes insipidus (DI) characterized by excess free water loss and dilute urine Central vs Nephrogenic Diabetes Inspidus (DI)Central DINephrogenic DIDefinitionFailure to produce antidiuretic hormone (ADH)Insensitivity or resistance of the kidneys to ADHEtiologyPituitary tumorOther pituitary injuriesautoimmune diseasetraumasurgeryischemiaDrugslithiumdemeclocyclineamphotericin BCongenital (rare)Electrolyte abnormalitieshypercalcemiahypokalemiaPathogenesis↓ ADH↑ADHVasopressin (DDAVP) challenge↓ Urine volume and ↑ urine osmolalityNo change in urine volume or osmolality Presentation Symptoms polyuria polydipsia nocturia thirst Studies Diagnostic testing studies 24-hour urine studies best initial test ↓ urine osmolality ↓ urine sodium ↑ urine volume water deprivation challenge no change in urine osmolality or volume vasopressin challenge central DI ↓ urine volume and > 50% ↑ in urine osmolality with DDVAP nephrogenic DI lack of response to vasopressin electrolytes hypernatremia Differential Primary polydipsia distinguishing factor hyponatremia after trial of desmopressin decreased urine output with water deprivation test Treatment Management approach treat underlying cause when appropriate remove offending agent if possible Central DI first-line desmopressin (DDAVP) mechanism ADH analog other hydration Nephrogenic DI first-line hydrochlorothiazide mechanism enhances sodium excretion over water excretion indomethacin mechanism may increase urine osmolality and water reabsorption amiloride indication lithium-induced nephrogenic DI mechanism reduces lithium uptake in the kidney other hydration low-sodium diet Complications Hypernatremia Dehydration