Differential Diagnosis of Polyuria

Title: Differential Diagnosis of Polyuria
Author: Robertson, Gary
Publisher: Annual Review of Medicine
Date Published: January 01, 1988
Reference Number: 473
Diabetes insipidus (DI) is a syndrome characterized by chronic polyuria and polydipsia. It can result from any of three basic defects: (a) inadequate urinary concentration caused by a deficiency in the secretion or action of the antidiuretic hormone vasopressin (neurogenic or nephrogenic DI), or excessive intake of water caused by a defect in (b) thirst or (c) psychological function (dipsogenic or psychogenic DI). These four types of DI can be differentiated clinically only if they present in a complete and classical form. However, more sophisticated diagnostic approaches involving assays of plasma vasopressin or closely monitored trials of antidiuretic therapy usually are necessary when the patient has mild or incomplete defects in thirst or vasopressin function. Accurate diagnostic differentiation among the four basic types of DI is essential not only for safe and effective management but also for a proper understanding of the basic physiology and pathophysiology of water homeostasis.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

The two main symptoms of diabetes insipidus (DI) are polyuria (the chronic passage of large volumes of urine) and polydipsia (chronic, excessive thirst). There are four types of DI:

  1. nephrogenic DI (NDI) caused by the kidneys' inability to respond to the antidiuretic hormone, arginine vasopressin (AVP);
  2. neurogenic or pituitary DI (PDI), caused by a deficiency of or an inability to synthesize or secrete AVP;
  3. dipsogenic DI, caused by a defect in the thirst mechanism that lowers the point at which a person feels thirsty, resulting in excessive water drinking; and
  4. psychogenic DI, caused by a cognitive defect associated with mental illness which leads to compulsive water drinking.

Types 3 and 4 both fall under the heading of primary polydipsia (PP).

Since the primary symptoms of all four types of DI are the same - polyuria and polydipsia - clinicians diagnose carefully to determine which form of DI their patient has because each type requires different treatment. These four types can be differentiated clinically only when they occur in the patient in their complete and classical form. If the patient should have a mild or incomplete form of DI, then more sophisticated diagnostic approaches are needed.

If a patient has polyuria, he will void more than two liters of urine over a 24-hour period. Further, that urine will be dilute. That is, the amount of osmotically active particles in the urine (e.g. sodium, sugars) will be small in proportion to the solvent (free water) portion of the urine. This measure is expressed in terms of osmotically active particles per kilogram of urine. In polyuria, the urine will have an osmolality of less than 300 mosmoles/kg.

Once it has been established that the patient is polyuric, and that the polyuria is not caused by diabetes mellitus, then the clinician can proceed with the next diagnostic step. This involves measuring the patient's plasma osmolality (the ratio of osmotically active particles to plasma solvent) during a time when the patient has free access to water. Alternatively, the patient's plasma sodium concentration can be measured under the same conditions. If these measures fall above normal, i.e., if the plasma or sodium is excessively concentrated, it is an indicator of either NDI or PDI. The next step is to measure the concentration of AVP in the patient's plasma and/or the patient's reaction to a synthetically modified form of AVP called DDAVP.

If the patient shows no or low levels of AVP in his plasma and if he responds to DDAVP by increasing the concentration of his urine, this is indicative of PDI. If the patient shows normal to slightly elevated levels of plasma AVP and does not respond to DDAVP with an increase in urine concentration, it is indicative of NDI. But if the polyuric patient's initial plasma osmolality and sodium measurements do not lie above normal, then the patient must undergo a carefully monitored period of no longer than 8 hours where he abstains from water. This test can be risky if not done properly and in most cases is best performed by a specialist or other physician experienced in its use.

During the time of this water fast, the patient's body weight, urine and plasma (or sodium) osmolalities should be measured hourly. If the patient's urine does not become more concentrated (i.e. if it does not rise above 300 mosmols/kg) before his plasma or sodium concentrations rise above normal, then the patient doesn't have primary polydipsia and should be given AVP or DDAVP. If the patient's urine osmolality increases by more than 50% in response to this, he has PDI. If it does not, he has NDI.

However, sometimes a polyuric patient's urine concentration will increase in response to the period of water deprivation. If it does, the patient could have PP, partial PDI or partial NDI. To distinguish which type of DI he may have, the clinician can take one of two approaches:

  1. continue the patient's water fast until his plasma or sodium osmolality rises above normal, then measure plasma AVP and plasma and urine osmolality;
  2. if the patient cannot tolerate prolonged water deprivation, give him an infusion of hypertonic (3%) saline and an infusion of aqueous Pitressin (a form of vasopressin), then measure plasma AVP and plasma and urine osmolality. Then the clinician can define more fully the relationship of plasma AVP to plasma or urine osmolality and interpret it in the same way as in the normal dehydration test.