A 35-year-old woman comes to the office due to frequent urination. She describes drinking excessive amounts of water due to unquenchable thirst. She does not take any medications. Her blood glucose level is 86 mg/dL. A standard water deprivation test is performed. The results of urine osmolality during 4 hours of dehydration are presented in the table below. The patient's plasma osmolality after 3 hours of water deprivation was found to be 298 mOsm/L, and vasopressin was then administered subcutaneously.
Time (hours) 1 2 3 4 Urine osmolality (mOsm/L) 90 100 100 790
Which of the following is the most likely diagnosis in this patient?
Show Explanatory Sources
The collecting duct is impermeable to water in the absence of vasopressin (antidiuretic hormone [ADH]). ADH activates G protein-coupled V2 receptors on the basolateral tubular cell membrane, stimulating phosphorylation of intracellular proteins. This causes fusion of vesicles containing aquaporin 2 to the luminal membrane, where aquaporin serves as a water channel and allows water reabsorption in the collecting duct.
Diabetes insipidus (DI) is caused by either ADH deficiency (central DI) or complete/partial unresponsiveness of the kidneys to ADH (nephrogenic DI). The end result is free water loss in the urine with production of dilute urine (low specific gravity and urine osmolality) and dehydration that causes excessive thirst. A water deprivation test with desmopressin (DDAVP) administration can differentiate between central and nephrogenic DI. In patients with central DI and complete nephrogenic DI, the urine osmolality is persistently low despite an increase in serum osmolality with water deprivation. When desmopressin is administered, patients with central DI show a rapid increase in urine osmolality and reduction in urine volume, whereas those with complete nephrogenic DI do not (Choice B).
(Choice C) Patients with partial nephrogenic DI have a slow but steady rise in urine osmolality with increasing serum osmolality after water deprivation. There is no further increase in urine osmolality with DDAVP, and the urine osmolality remains low (<500 mOsm/L).
(Choice D) Relief of urinary obstruction (eg, Foley catheterization in patients with benign prostatic hyperplasia) may result in post-obstructive diuresis as the kidneys act to normalize fluid volume and solute levels. It is mostly seen in patients with a history of reduced urine output from chronic urinary obstruction. Urine osmolality remains within normal limits.
(Choice E) Patients with primary polydipsia exhibit an increase in serum and urine osmolality on water deprivation that is similar to partial nephrogenic DI. However, the correction in primary polydipsia is more rapid, and the urine osmolality returns to a level closer to normal (but still submaximal due to washout of the medullary osmotic gradient). A history of psychiatric disorders or medication-induced xerostomia is usually present.
Educational objective:
Patients with diabetes insipidus (DI) are unable to concentrate their urine in response to dehydration. Following desmopressin administration during the water deprivation test, urine osmolality increases to normal levels in central DI but does not change in complete nephrogenic DI.