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Flushing out the truth about diabetes insipidus

Simmons, Susan PhD, RN, ARNP-BC

doi: 10.1097/01.NURSE.0000365921.24254.4a

Refresh your knowledge of what to do when your patient's fluids are out of balance.

Susan Simmons is a nurse practitioner at the Walk-In Healthcare of Olathe, Kan., and Quivera Family Care in Overland Park, Kan.

Here's what to do when your patient's fluids get out of balance.



JOHN, 20, IS IN THE ICU after suffering a head injury in a motor vehicle crash. His urine output, which averaged 30 to 50 mL/hour, has suddenly increased to more than 300 mL/hour over the past 2 hours, and the urine specific gravity has dropped to less than 1.005.

Mary, 42, arrives in the ED complaining of weakness, dizziness, fatigue, and urinary frequency. Her urine specific gravity is less than 1.005. She has a longstanding history of bipolar disorder, which has been treated with lithium.

What do these two patients have in common besides polyuria and a low urine specific gravity? Both patients have diabetes insipidus (DI). John's case of DI is central, related to a recent head trauma; Mary's case is nephrogenic in origin and a result of lithium toxicity.

Fortunately, DI is rare, affecting only 1 in 25,000 patients, but if it occurs, you'll need to be ready to intervene quickly to prevent cardiovascular collapse and death. This articlewill describe how to recognize and respond to these two common types of DI in adults.

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Defining DI

In a healthy patient, antidiuretic hormone (ADH, also called arginine vasopressin) is produced in the hypothalamus, stored in the posterior pituitary, and secreted to maintain serum osmolality. For example, ADH is released in response to conditions that cause an increase in serum osmolality, such as dehydration, hypotension, electrolyte imbalances, and even hypoxia. The hormone targets the kidney's cortical and medullary collecting tubules by increasing their permeability to water, leading to water retention. This increase in free water in turn increases intravascular volume and BP, and returns serum osmolality to normal.1

DI results from an abnormal decrease in secretion or action of ADH. There are several types; this article will focus on the two most common. Central DI occurs when osmoreceptors located on the hypothalamus become damaged and serum osmolality can't be maintained. (For causes of two common types of DI, see Upsetting the balance.) In some cases, central DI can also result when the posterior pituitary can't release ADH. Central DI is the more common form. It's typically idiopathic or results from surgery or trauma to the head in the area of the pituitary or hypothalamus.

Central DI can be transient, permanent, or (most often) triphasic. The first phase of triphasic DI lasts 4 to 5 days and is characterized by polyuria and a falling urine specific gravity. The second phase lasts 5 to 6 days and is associated with antidiuresis as stored ADH is released. In the third phase, ADH can no longer be released, either because stores are exhausted or the damaged hypothalamus can't produce more ADH. The third stage, if not treated, can lead to permanent DI.

Nephrogenic DI occurs if the kidney becomes resistant to ADH's urine-concentrating properties. This less-common form of DI usually is related to lithium use or hypercalcemia in adults.

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Recognizing the signs and symptoms

Whether the cause of DI is central or nephrogenic, you'll see the same signs and symptoms:

  • polydipsia (excessive thirst)
  • polyuria (excessive urination, defined as more than 3 L/day of urine in an adult.)2 Normal urine output in an adult is 1 to 1.5 L/day. Lab testing will reveal decreased urine specific gravity (normal range is 1.005 to 1.030) and decreased urine osmolality (average normal range is 200 to 800 mOsm/kg H2O mOsm/L).
  • signs and symptoms of dehydration such as dry, cracked lips; inability to produce tears; fever; orthostatic hypotension; weakness; dizziness; fatigue; and weight loss
  • signs and symptoms of hypernatremia secondary to increased serum osmolality, including restlessness, agitation, decreased deep tendon reflexes, and seizures. Normal serum sodium is 135 to 145 mEq/L; normal serum osmolality is 280 to 300 mOsm/kg. In a patient with DI, serum sodium will exceed 145 mEq/L and serum osmolality will be above 300 mOsm/kg.

When a clinician suspects DI, the diagnosis is confirmed via lab and other diagnostic testing. In cases in which the cause of DI may not be known, magnetic resonance imaging of the brain and pituitary may be done to rule out other causes, such as a tumor. To distinguish between central and nephrogenic DI, the clinician may order one of two tests:

  • In the water deprivation test, all water is withheld from the patient and urine osmolality and weight are measured hourly. When two sequential urine osmolality readings vary by less than 30 mOsm (or less than 10%) or the patient's weight drops 3%, aqueous vasopressin is administered. A final urine specimen is taken 60 minutes later for an osmolality measurement. Weight loss and decreased serum osmolality indicate that the kidneys can't concentrate urine and DI is nephrogenic. If the kidneys can concentrate urine, the DI is central.3

This test shouldn't be performed in critically ill patients who'd be at risk for cardiovascular collapse from severe volume loss.1

  • In the ADH test, the patient is given exogenous ADH (as above, but without fluids being withheld) and urine volume is measured before and after the challenge. Findings indicative of DI are similar to those above with the water deprivation test. Fluid intake should be consistent. Although this test is less likely than the water deprivation test to lead to severe dehydration, it's still not considered an appropriate test for critically ill patients.1
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Treatment goals

Treatment goals for a patient with DI include identifying and treating the underlying cause of the DI if possible; maintaining adequate hydration and electrolyte balance; and avoiding hyperglycemia, fluid overload, and too-rapid correction of hypernatremia.1,3,4 (Correcting hypernatremia too rapidly can lead to cerebral edema or myelinolysis.) Monitor the patient's intake, output, and urine specific gravity hourly.

The first 50% of the patient's water deficit is replaced over the first 12 to 24 hours, with the remaining 50% given over the following 1 to 2 days. The choice of fluid used for fluid replacement depends on the patient's water deficit and his serum and urine electrolytes. The patient's sodium levels are brought to normal via fluid replacement aimed at reducing sodium levels by about 0.5 mmol/L/hour. Monitor the patient's blood glucose to avoid hyperglycemia, which increases urine output via glycosuria and can be confused with polyuria caused by DI.



A patient with central DI will need ADH replacement, which typically is given via intranasal desmopressin acetate (DDAVP). Other routes of administration are available, but the intranasal route is less likely to cause hypertension or dysrhythmias because intranasal desmopressin acetate has no effect on smooth muscle. The intranasal form also is better absorbed and hasn't been found to lead to the production of antivasopressin antibodies. Oral desmopressin must be taken on an empty stomach or absorption is reduced by 40% to 50%.1,4

Treatment of nephrogenic DI can include the use of thiazide diuretics or nonsteroidal anti-inflammatory drugs (NSAIDs). Thiazide diuretics decrease urinary volume when ADH is absent, leading to sodium and water retention. Diuretics also may let water be reabsorbed at the proximal tubule rather than in the collecting ducts, where water reabsorption is under the influence of ADH.

NSAIDs, through prostaglandin inhibition, reduce the urine volume by reducing solute delivery to the distal tubules. Not all NSAIDs are equally effective in each patient, and so trial and error may be needed to find the appropriate agent.4

Patients with nephrogenic DI also should be put on a low-sodium (2.3 g/day) and low-protein diet (1 g/kg/day or less). In combination with medications, this diet can reduce urine output up to 50%. A greater response to thiazide therapy can be achieved by adding a potassium-sparing diuretic such as amiloride. This combination is particularly helpful in patients whose DI is related to lithium overload, because the drugs keep lithium from entering the collecting tubules and blocking the action of ADH.4,5

Chlorpropamide and, rarely, clofibrate may be used to treat nephrogenic DI. Chlorpropamide helps sensitize the kidneys to ADH; both drugs help relieve thirst and decrease urine output by up to 50%.3,4 Monitor blood glucose levels closely if the patient is taking chlorpropamide, and be prepared to intervene quickly if signs and symptoms of hypoglycemia develop.

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Monitoring your patient

Assess your patient's vital signs frequently and monitor intake and output and urine specific gravity hourly. Also assess hourly for signs and symptoms of fluid volume overload, such as pulmonary crackles. Lab monitoring includes serum chemistries (including blood urea nitrogen, creatinine, sodium, and potassium) and urine specific gravity.1 As DI resolves, the patient will need less fluid resuscitation and medication.

If the cause of the DI is identified, treated appropriately, and can be reversed, the patient may fully recover from DI. If the cause can't be identified or reversed, the patient may develop chronic DI, and will need lifelong medication. Teach patients to carefully monitor their weight, medications, and alcohol use, and to see their healthcare provider regularly. Although chronic DI can be frightening for patients, it hasn't been found to shorten lifespan.1

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Wrapping things up

Now let's return to the patients we met at the beginning of this article. John, who has a head injury, is in the ICU and on mechanical ventilation. A pulmonary artery (PA) catheter was placed to monitor his hemodynamic status; monitor him carefully to avoid fluid volume overload that could lead to cerebral and pulmonary edema. Administer fluid replacement as ordered. Closely monitor his level of consciousness, vital signs, PA pressures, urine output, urine osmolarity, and volume status.

John is administered intranasal desmopressin to treat his central DI. Monitor his electrolytes, renal function, and serum glucose closely. His DI resolves, and he remains in the ICU for treatment of his head injury.

Mary, who has nephrogenic DI, is admitted to the ICU for close monitoring. In taking her history, you learn that she recently doubled her dose of lithium without telling her psychiatrist and without having her lithium levels checked. The higher dose of lithium led to DI. Her psychiatrist is notified and will consider prescribing another medication for Mary's bipolar disease.

Because NSAIDs may increase lithium levels, they're not indicated to treat Mary's DI. Using a hypoglycemic agent is also considered risky because of the risk of hypoglycemia.

After 4 days in the ICU, Mary's DI resolves and she's transferred to a monitored unit, where she'll learn about her diet, fluid intake, new medications, and how to avoid relapses of DI. She'll be followed closely after discharge by her psychiatrist and her primary care provider.

By understanding these two types of DI and how their treatment differs, you can help patients recover from acute DI and manage chronic DI.

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Upsetting the balance6,7

Causes of central DI

  • Idiopathic
  • Head: neurotrauma, neurosurgery, tumors, anoxic encephalopathy, cerebral aneurysm, cavernous sinus thrombosis
  • Infections affecting the central nervous system: tuberculosis, syphilis, mycoses, toxoplasmosis, encephalitis, meningitis
  • Infiltrative disorders: sarcoidosis, histiocytosis X (multifocal Langerhans cell granulomatosis)
  • Pregnancy-related: vasopressinase-induced, acute fatty liver of pregnancy
  • Congenital and familial: Wolfram syndrome
  • Other: post-supraventricular tachycardia, anorexia nervosa
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Causes of nephrogenic DI

  • Medications: lithium, amphotericin B, phenytoin, corticosteroids, anticholinergics, rifampin, aminoglycosides
  • Alcohol
  • Electrolyte imbalances: hypercalcemia, hypokalemia
  • Chronic tubulointerstitial diseases: analgesic nephropathy, sickle-cell disease, multiple myeloma, amyloidosis, sarcoidosis, Sjogren syndrome, systemic lupus erythematosus, polycystic kidney disease, pyelonephritis, medullary cystic disease, acute tubular necrosis
  • Congenital: vasopressin V2 receptor defect, aquaporin-2 water channel defect
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1. Holcomb SS. Diabetes insipidus. Dimens Crit Care Nurs. 2002;2194–2197.
2. Rose BD, Bichet DG. Diagnosis of polyuria and diabetes insipidus. UpToDate. January 7, 2009 .
3. Cooperman M. Diabetes insipidus .
4. Rose BD. Treatment of central diabetes insipidus. UpToDate. January 7, 2009 .
5. Rose BD, Bichet DG. Treatment of nephrogenic diabetes insipidus. UpToDate. January 2, 2009 .
6. Rose BD. Causes of nephrogenic diabetes insipidus. UpToDate. May 27, 2009 .
7. Rose BD. Causes of central diabetes insipidus. UpToDate. November 3, 2008 .
© 2010 Lippincott Williams & Wilkins, Inc.