Snapshot A 30-year-old woman presents to her primary care physician for increased frequency of urinating, thirst, and urinating at night. She was in a car accident about a month ago, where she had head trauma. Since then, she reports that she has noticed this increased frequency of urination. At that time, head imaging had been normal. Her physician decides to conduct a vasopressin challenge. The results show decreased urine volume and increased urine osmolality. Based on these results, she decides to start the patient on desmopressin. (Central diabetes insipidis) Introduction Clinical definition diabetes insipidus (DI) characterized by excess free water loss and dilute urine Central vs Nephrogenic Diabetes Inspidus (DI) Central DI Definition Failure to produce antidiuretic hormone (ADH) Insensitivity or resistance of the kidneys to ADH in the collecting duct Etiology Pituitary tumor, where vasopressin is released Other pituitary injuries autoimmune disease trauma surgery ischemia Drugs lithium demeclocycline amphotericin B Congenital (rare) Electrolyte abnormalities hypercalcemia hypokalemia Pathogenesis ↓ ADH, resulting in increased extracellular fluid osmolarity ↑ADH Vasopressin (DDAVP) challenge ↓ Urine volume and ↑ urine osmolality No change in urine volume or osmolality Presentation Symptoms polyuria polydipsia nocturia thirst Studies Serum labs ↑ serum osmolarity (central DI) electrolytes hypernatremia Other tests 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 Differential Primary polydipsia distinguishing factor hyponatremia after trial of desmopressin increased urine osmolality with water deprivation test Treatment Lifestyle hydration low sodium diet nephrogenic DI Medical desmopressin (DDAVP) mechanism ADH analog that act on the renal tubular cells to increased water permeability this, in turn, increases water retention indication central DI hydrochlorothiazide mechanism induces mild hypovolemia induces an increase in proximal water and sodium reabsorption indication nephrogenic DI indomethacin mechanism inhibits prostaglandin synthesis prostaglandin synthsis are ADH antagonists indication nephrogenic DI amiloride mechanism epithelial sodium channel inhibitor and is believed to impair lithium entry into the renal pricipal cells indication nephrogenic DI secondary to lithium toxicity Complications Hypernatremia Dehydration