This patient is suffering from diabetes insipidus (DI). In a standard desmopressin test, an increase in urine osmolality of greater than 10% is highly suggestive of a diagnosis of central DI.
Central DI is characterized by the failure of the hypothalamic-pituitary axis to produce and secrete sufficient levels of the hormone vasopressin (ADH). A desmopressin test is a highly useful diagnostic tool to differentiate between central (described above) and nephrogenic (resistance to ADH action in the kidneys) DI. The test involves injection of exogenous vasopressin. In central DI, injection of exogenous vasopressin will act to rectify the inappropriately low levels of endogenous ADH, leading to an increase in urine osmolality towards the normal range. In contrast, injection of ADH in the setting of nephrogenic ADH will not have any notable effect, as increasing ADH levels will not overcome the disease mechanism of renal resistance to ADH action.
Adam describes the diagnostic protocol of DI in which the desmopressin test can help distinguish neurogenic from nephrogenic cases of DI. The treatment of neurogenic DI may involve nasal administration of desmopressin while nephrogenic DI requires hydration and the administration of thiazides and amiloride.
Thompson et al. describe the normal physiological action of ADH, which is to recruit aquaporin channels in the renal distal tubules and collecting ducts, leading to increased reabsorption of water and an improved ability to excrete concentrated urine. Thus, both forms of diabetes insipidus manifest with symptoms of dehydration and inappropriate excretion of excessive volumes of dilute urine.
Illustration A depicts urine osmolality and response to water deprivation and desmopressin test in both central and nephrogenic DI.
Answer 1 & 2: Central DI should demonstrate an increase in urine osmolality of 10% or more in a standard water deprivation test.
Answer 3: Although this test result demonstrates a slight increase in urine osmolality, it is less than a 10% increase and therefore is indicative of nephrogenic DI.
Answer 5: This finding is characteristic of nephrogenic DI, as urine osmolality changes less than 10% during a standard desmopressin test. A normal or elevated level of ADH to accompany this desmopressin test result would increase suspicion of nephrogenic DI even further.
Adam P. Evaluation and management of diabetes insipidus. Am Fam Physician. 1997 May 1;55(6):2146-53.
PMID:9149642 (Link to Abstract)
Thompson C, Hoorn EJ. Hyponatraemia: an overview of frequency, clinical presentation and complications. Best Pract Res Clin Endocrinol Metab. 2012 Mar;26 Suppl 1:S1-6.
PMID:22469246 (Link to Abstract)
USMLE World Step 1 QBank Question #211. Copyright © USMLEWorld, LLC 2012