Copyright © 2003 The Diabetes Insipidus Foundation, Inc.

 

Polyuria and Polydipsia

Think of Diabetes Insipidus (DI) -

not just Diabetes Mellitus

Importance

    Although diabetes mellitus is widely recognized as the commonest cause of polyuria and polydipsia, the possibility of diabetes insipidus (DI) is too often overlooked by physicians.  It is very important to bear DI in mind because missing the diagnosis can lead to needless suffering by patients and their families; indeed, failure to make the diagnosis can result in severe dehydration with irreversible brain damage, even death.  Moreover, DI can be an early sign of serious underlying disease, such as a brain tumor.

    Experiences by patients with DI have been gathered by three organizations: The Diabetes Insipidus Foundation, Inc. (DiF), the Nephrogenic Diabetes Insipidus Foundation ((NDIF), and the NDI Network.  The histories attest to numerous instances where the diagnosis of DI was missed - sometimes for years -  when ultimately the correct diagnosis led to effective treatment.

    Beyond the need for correct diagnosis and treatment, it is important for physicians to be aware of DI because current research utilizing molecular and cell-biological techniques is providing new insights into DI that could soon lead to more specific and more effective treatment.

Forms of DI

    The term Diabetes Insipidus refers to an abnormal state of water diuresis (as opposed to an abnormal state of osmotic diuresis, as in diabetes mellitus); DI is characterized by a large volume of dilute urine (hypotonic polyuria) associated with increased fluid intake (polydipsia).  It is now known that there are four types of DI: (1) neurogenic (or central) DI, where the water diuresis results from a deficiency of the antidiuretic hormone (ADH), often referred to as AVP (arginine vasopressin); (2) nephrogenic DI, where water diuresis results from an inability of the kidneys to respond to ADH; (3) primary polydipsic DI (or primary polydipsia) in which the water diuresis is due to suppression of ADH by excessive fluid intake [the high intake can result from abnormal thirst (dipsogenic DI), from psychological or emotional disturbances (psychogenic DI) or from fashionable - but scientifically unproven - beliefs in the benefits of a high fluid intake (iatrongenic DI)]; (4) gestagenic DI, which occurs only during pregnancy and is due to destruction of vasopressin by the placenta.

Causes of DI

Among some of the major causes are the following:

  1. Neurogenic: acquired: brain tumors; head trauma; granulomatous diseases; autoimmunity; idiopathic inherited: autosomal dominant or recessive mutation in the vasopressin gene; X-linked recessive mutation in an unknown gene

  2. Nephrogenic: acquired: hypokalemia; hypercalcemia; lithium inherited: X-linked recessive mutation in vasopressin receptor; autosomal recessive or dominant   mutation in water channel

  3. Polydipsic: acquired: idiopathic (most); chronic meningitis; granulomatous diseases; multiple sclerosis or   other diffuse pathology of the brain; psychiatric illness

  4. Gestagenic: acquired: pregnancy

Guidelines for Diagnosis

Urinary frequency, nocturia, enuresis, and frequent or constant thirst should arouse suspicion of DI.

Caution: Nephrogenic DI commonly occurs at birth, when thirst and polyuria will be signaled as unexplained fussiness or inconsolable crying, unusually wet diapers, frequent nursing often accompanied by fever, dry skin with cool extremities, and failure to thrive.  These signs and symptoms should arouse suspicion of polyuria/polydipsia in any infant or young child who cannot yet verbalize her/his complaints.

On the basis of a good history and appropriate tests, rule out diabetes mellitus, the most common cause of polyuria/polydipsia.  Usually, absence of glucose in the urine, as determined by Dipstick, will suffice.

If possible, collect 24-hour urine into clean, 1 gallon, plastic milk containers during ad libitum fluid and food intake.  A total volume of more than 3 quarts (40 ml/kg body weight per day or higher in adults and older children) with an osmolality below 300 mOsm/kg H20 (specific gravity <1.010) warrants further evaluation for DI.  In infants or young children who are not yet toilet trained, it may be easier to measure fluid intake; an intake of approximately 1 1/2 to 2 quarts per day (100 ml/kg body weight per day or more) will be strongly suggestive of DI.  An effort should then be made to differentiate among the forms of DI, as follows:

Measure plasma sodium concentration during ad libitum fluid and food intake.

If plasma sodium is above normal while urine osmolality is below 300 mOsm/kg H20:

Measure the urine osmolality of a spontaneously voided urine sample.  Immediately thereafter, give an injection of desamino, d-arginine vasopressin (dDAVP) -- 1 to 3 micrograms subcutaneously (depending on age and body weight) and measure urine osmolality 1 to 2 hours later (or of the next spontaneously voided sample).

If the urine osmolality rises by 50% or more (e.g., from 280 mOsm/kg H20 before dDAVP to 420 mOsm/kg H20 or higher after dDAVP), then a diagnosis of neurogenic DI (pituitary or central DI) is likely.

If the urine osmolality rises by less than 50%, then nephrogenic DI may be present.

If plasma sodium is normal while urine osmolality is below 300 mOsm/kg H20, additional procedures, including a water deprivation test (sometimes with hypertonic saline infusion), will be needed for differential diagnosis.  A protocol for this test can be found on this website.

However, because this test can be difficult - it usually requires constant monitoring with serial, simultaneous measurement of plasma sodium and plasma osmolality, plasma vasopressin, body weight, and urine osmolality - we recommend that it be performed by an experienced specialist.  Information about medical centers equipped to carry out and interpret the water deprivation test can be obtained through the following websites, which also provide useful information and support for DI patients and their families:

The DiF

the NDIF

It is also important to look for the cause of DI.  If it is neurogenic or dipsogenic, and MRI  of the brain and tests of anterior pituitary function are usually indicated.  If the DI began during infancy or childhood or affects other family members, a genetic analysis should be performed.

References

Bichet, D.G. Diabetes insipidus and vasopressin.  In: Diagnostic Endocrinology, 2nd ed, edited by W.T. Moore and R.C. Eastman.  St. Louis: Mosby-Year Book, 1996, pp 157-175.

Moses, A.M., B. Clayton, and L. Hochhauser.  Use of T1-weighted MR imaging to differentiate between primary polydipsia and central diabetes insipidus.  Am J Neuro Res 13:1273-1277, 1992.

Robertson, G.L., Disorders of Neurohypophysis. In: Harrison's Principles of Internal Medicine, edited by E. Braunwald, A.S. Fauci, D.L. Kasper, S.L. Hauser, D.L. Longo, and J.L. Jameson.  New York: McGraw-Hill, 2001, pp 2052-2060.
Last Updated December 2006