endocrine and metabolic disorders
ArginineVasopressin Deficiency (Central Diabetes Insipidus)
Diagnosis ofArginineVasopressinDeficiency
Water deprivation test Sometimesvasopressinor copeptin levels Argininevasopressindeficiency must be differentiated from other causes of polyuria, particularly primary polydipsia (see table) andargininevasopressinresistance. All tests forargininevasopressindeficiency (and forargininevasopressinresistance) are based on the principle that increasing the plasma osmolality in normal people will lead to decreased excretion of urine with increased urine osmolality. Mechanism Example Vasopressin-sensitive polyuria Vasopressin-sensitive polyuria Decreased synthesis ofvasopressin Primaryargininevasopressindeficiency, hereditary (usually autosomal dominant) Acquired (secondary)argininevasopressindeficiency (causes outlined in text) Primary diabetes insipidus, hereditary associated with diabetes mellitus, optic nerve atrophy, nerve deafness, and atonia of bladder and ureters (Wolfram syndrome) Decreased release ofvasopressin Primary polydipsia (dipsogenic diabetes insipidus) Vasopressin-resistant polyuria Vasopressin-resistant polyuria Renal resistance tovasopressin Congenital Nephrogenic Diabetes Insipidus (usually X-linked recessive trait) resistance: Chronic Kidney Disease , systemic or metabolic disease (eg, Osmotic diuresis Hyperglycemia (in Diabetes Mellitus (DM) ) Poorly resorbed solutes (mannitol,sorbitol,urea) Water deprivation test None The test is started in the morning by weighing the patient, obtaining venous blood to determine electrolyte concentrations and osmolality, and measuring urinary osmolality. Voided urine is collected hourly, and its specific gravity or, preferably, osmolality is measured. Dehydration is continued until orthostatic hypotension and postural tachycardia appear,≥5% of the initial body weight has been lost, or the urinary concentration does not increase>0.001 specific gravity or>30 mOsm/L in sequentially voided specimens. Serum electrolytes and osmolality are again determined. Exogenousvasopressinis then given (5 units of aqueousvasopressinsubcutaneously, 10 mcgdesmopressin[DDAVP] intranasally, or 4 mcg IM or IV). Urine for specific gravity or osmolality measurement is collected one final time 60 minutes postinjection, and the test is terminated. A normal response produces maximum urine osmolality after dehydration (often>1.020 specific gravity or>700 mOsm/kg [700 mmol/kg]), exceeding the plasma osmolality; osmolality does not increase more than an additional 5% after injection ofvasopressin. Patients withargininevasopressindeficiency are generally unable to concentrate urine to greater than the plasma osmolality but are able to increase their urine osmolality by>50 to > 100% after exogenousvasopressinadministration. Patients with partialargininevasopressindeficiency are often able to concentrate urine to above the plasma osmolality but show a rise in urine osmolality of 15 to 50% aftervasopressinadministration. Patients withargininevasopressinresistance are unable to concentrate urine to greater than the plasma osmolality and show no additional response tovasopressinadministration (see table). Measurement of circulatingvasopressinor copeptin, the C-terminal peptide end ofvasopressin, is the most direct method of diagnosingargininevasopressindeficiency; levels ofvasopressinand copeptin at the end of the water deprivation test (before thevasopressininjection) are low inargininevasopressindeficiency and appropriately elevated inargininevasopressinresistance. However,vasopressinand copeptin levels are difficult to measure, and the tests are not routinely available. In addition, the physiologic response to water deprivation is so accurate that direct measurement ofvasopressinor copeptin is unnecessary. Plasmavasopressinor copeptin levels are only diagnostic after either dehydration or infusion of hypertonic saline. The water deprivation test should be done while the patient is under constant supervision because serious dehydration may occur. Parameter Normal CompleteArginineVasopressinDeficiency PartialArginineVasopressinDeficiency CompleteArginineVasopressinResistance PartialArginineVasopressinResistance Primary Polydipsia Uosm after dehydration (step 1) Very high (> 700–800 mOsm/kg [> 700–800 mmol/kg]) Very low (less than plasma osmolality) Low (≥ 300 mOsm/kg [≥ 300 mmol/kg]) Very low (less than plasma osmolality) Very low (less than plasma osmolality) High (500–600 mOsm/kg [500–600 mmol/kg]) Uosm increase aftervasopressin(step 2) Minimal (< 5%) 50 to > 100% 15–50% < 50 mOsm/kg (<50> Up to 45% No change Uosm = urine osmolality. resistance, patients with primary polydipsia usually do not have nocturia, nor does their thirst wake them at night. Continued ingestion of large volumes of water in this situation can lead to life-threatening Hyponatremia . Patients with acute excessive water drinking are able to concentrate their urine during water deprivation. However, because chronic water intake diminishes medullary tonicity in the kidneys, patients with long-standing polydipsia are not able to concentrate their urine to maximal levels during water deprivation, a response similar to that of patients with partialargininevasopressindeficiency. However, unlikeargininevasopressindeficiency, patients with primary polydipsia show no response to exogenousvasopressinafter water deprivation. This response resembles that ofargininevasopressinresistance, except that basalvasopressinlevels are low compared with the elevated levels present inargininevasopressinresistance. After prolonged restriction of fluid intake to≤2 L/day, normal concentrating ability returns within several weeks. 