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Diagnosis and characterization of diabetes insipidus
Diagnosis of psychogenic water intoxication
As an adjunct in the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone secretion (SIADH), including ectopic arginine vasopressin production
Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a hypothalamic polypeptide that is transported along the axons of the synthesizing neurons into the posterior pituitary gland. From there it is released into the systemic circulation after appropriate stimuli. The main regulators of AVP secretion are osmotic stimuli, provided by osmoreceptors located in the anteromedial hypothalamus, and volume stimuli, provided by receptors in neck vessels and heart. Under physiological conditions, volume stimuli always override osmotic stimuli.
The absence or presence of AVP is the major physiologic determinant of urinary free water excretion or retention. AVP acts principally on renal collecting tubules to increase water reabsorption. The antidiuretic effects of AVP are mediated by V2 vasopressin receptors. AVP can also increase vascular resistance through stimulation of V1 receptors.
Diabetes insipidus (DI) is characterized by the inability to appropriately concentrate urine in response to volume and osmol stimuli. The main causes for DI are decreased AVP production (central DI) or decreased renal response to AVP (nephrogenic DI).
AVP can also be secreted inappropriately in certain situations, particularly in elderly patients, leading to water retention and dilutional hyponatremia. Inappropriate AVP secretion might be observed with central nervous system pathology, such as head injury, stroke, or cerebral tumor, or as a side effect of central acting drugs that interfere with the hypothalamic regulation or AVP. Noncentral causes of inappropriate AVP secretion include peripheral stimuli that mimic central vascular hypovolemia, in particular severe low-output cardiac failure, and ectopic AVP secretion (usually by a bronchogenic carcinoma).
Adults: <1.7 pg/mL
Reference values were determined on platelet-poor EDTA plasma from individuals fasting no longer than overnight.
Central DI can be differentiated from nephrogenic DI by measuring arginine vasopressin (AVP) during a state of maximal, or near maximal, stimulus for AVP release (water deprivation test: perform under medical supervision; stop once plasma osmolality >295 mOsm/kg water or > or =5% loss in body weight) and assessing the antidiuretic response to exogenous administration of the AVP at the conclusion of a water deprivation test:
-If AVP is low despite elevated serum osmolality, and the urine osmolality increases significantly after administration of exogenous AVP, the diagnosis is compatible with central DI.
-If stimulated AVP is elevated and the administration of exogenous AVP results in little or no increase in urine concentration, the patient likely has nephrogenic DI.
-Mixed forms of DI can exist, and both central and peripheral DI may be incomplete, complicating the interpretation of results.
Patients with psychogenic polydipsia will either have a normal response to water deprivation or, in particular in long-standing cases, will show a pattern suggestive of mild nephrogenic DI due to loss of concentrating gradient across the nephron as a result of salt-washout by long-standing polydipsia.
An elevated plasma AVP level in a hyponatremic, euvolemic patient might be indicative of SIADH. Confirmation of euvolemia is critical in such patients, since an elevated AVP level represents a physiological response to hypovolemia.
Seizures, cerebral hemorrhages, cerebral trauma, cerebral tumors, neurosurgery, electroconvulsive therapy, central nervous system acting drugs, and a variety of conditions that reduce apparent blood volume or pressure in central vessels (eg, severe low output cardiac failure) can all result in inappropriate AVP elevations. Depending on the clinical course, these might be short lived. If none of these conditions is present, ectopic AVP secretion, most commonly caused by bronchial carcinoma, should be suspected.
Reference values were determined on platelet-poor EDTA plasma from individuals fasting no longer than overnight. A significant amount of circulating arginine vasopressin (AVP) is associated with platelets. Therefore, various conditions affecting platelets may also affect AVP levels. Platelet-rich specimens have been shown to have AVP levels on the order of 10 times the value of platelet-poor specimens.
AVP levels obtained in the process of a water deprivation test can be difficult to interpret because of the many non standardized variables in this test. Expert consultation is recommended in these circumstances.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. A recommended time period before collection cannot be made because it will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive samples received in the laboratory will be held and assayed after the radioactivity has sufficiently decayed. This will result in a test delay.
Robertson GL: Antidiuretic hormone. Normal and disordered function. Endocrinol Metab Clin North Am 2001 September;30(3):671-694