DIABETES INSIPIDUS

DEFINITION: Diabetes insipidus is a condition in which the body cannot retain enough water. The patient is excessively thirsty and excretes large amounts of extremely diluted urine - a reduction in fluid intake does not reduce amounts and consistency of urine excretion. It is a rare condition, affecting approximately 1 in every 25,000 people. Diabetes insipidus is not related to diabetes mellitus (sugar diabetes). The term diabetes on its own nearly always refers to diabetes mellitus In most cases diabetes insipidus occurs because the body does not properly produce, store or release a key hormone - arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). It may also occur when the kidneys do not respond properly to ADH (antidiuretic hormone).

According to Medilexicon's medical dictionary:

Diabetes insipidus is "Chronic excretion of very large amounts of pale urine of low specific gravity, causing dehydration and extreme thirst; ordinarily results from inadequate output of pituitary antidiuretic hormone; the urine abnormalities may be mimicked as a result of excessive fluid intake, as in psychogenic polydipsia. Two types exist: central and nephrogenic. Autosomal dominant [MIM*125700, *125800, *192340], X-linked [MIM*304800 and *304900], and even autosomal recessive forms [MIM*222000] have been described." DIFFERENT TYPES Central Diabetes Insipidus The most common form of serious diabetes insipidus, central diabetes insipidus, results from damage to the pituitary gland, which disrupts the normal storage and release of ADH. Damage to the pituitary gland can be caused by different diseases as well as by head injuries, neurosurgery, or genetic disorders. To treat the ADH deficiency that results from any kind of damage to the hypothalamus or pituitary, a synthetic hormone called desmopressin can be taken by an injection, a nasal spray, or a pill. While taking desmopressin, a person should drink fluids only when thirsty and not at other times. The drug prevents water excretion, and water can build up now that the kidneys are making less urine and are less responsive to changes in body fluids. Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus results when the kidneys are unable to respond to ADH. The kidneys' ability to respond to ADH can be impaired by drugs-like lithium, for example-and by chronic disorders including polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders. Sometimes the cause of nephrogenic diabetes insipidus is never discovered. Desmopressin will not work for this form of diabetes insipidus. Instead, a person with nephrogenic diabetes insipidus may be given hydrochlorothiazide (HCTZ) or indomethacin. HCTZ is sometimes combined with another drug called amiloride. The combination of HCTZ and amiloride is sold under the brand name Moduretic. Again, with this combination of drugs, one should drink fluids only when thirsty and not at other times. Dipsogenic Diabetes insipidus Dipsogenic diabetes insipidus is caused by a defect in or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Desmopressin or other drugs should not be used to treat dipsogenic diabetes insipidus because they may decrease urine output but not thirst and fluid intake. This fluid overload can lead to water intoxication, a condition that lowers the concentration of

sodium in the blood and can seriously damage the brain. Scientists have not yet found an effective treatment for dipsogenic diabetes insipidus. Gestational Diabetes Insipidus Gestational diabetes insipidus occurs only during pregnancy and results when an enzyme made by the placenta destroys ADH in the mother. The placenta is the system of blood vessels and other tissue that develops with the fetus. The placenta allows exchange of nutrients and waste products between mother and fetus. Most cases of gestational diabetes insipidus can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational diabetes insipidus, and desmopressin should not be used. CAUSE & RISK FACTORS: Diabetes insipidus has several causes. In some people, a part of the brain (called the hypothalamus) doesn't make enough antidiuretic hormone (ADH). ADH helps your body balance water in the urine and blood. In other cases, the pituitary gland (which is responsible for releasing the ADH into the body) doesn't release enough of the hormone. Damage to either the hypothalamus or the pituitary gland can cause diabetes insipidus. This can occur after a head injury, during brain surgery or when a tumor grows on the glands. Abnormalities in the kidneys can also cause diabetes insipidus. If the kidneys are abnormal, it can affect the way they process ADH. Diabetes insipidus can be caused by some medicines, such as lithium. About 30% of the time, doctors can't find the cause. ADH controls the amount of water reabsorbed by the kidneys. ADH is made in the hypothalamus of the brain. The pituitary gland , at the base of the brain, stores and releases ADH.

The following factors increase your chance of developing diabetes insipidus:

Damage to the hypothalamus due to surgery, infection, tumor, or head injury Polycystic kidney disease or another kidney disease that may affect the filtration process Use of certain medications such as lithium, amphotericin B, or demeclocycline High blood levels of calcium Low blood levels of potassium

Nephrogenic diabetes insipidus that's present at or shortly after birth usually has a genetic cause that permanently alters the kidneys' ability to concentrate the urine. Nephrogenic DI usually affects males, though women can pass the gene on to their children. SIGN AND SYMPTOMS: A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign. The main signs and symptoms of diabetes insipidus include:

Extreme thirst - patients find themselves having to drink water all the time. The constant thirst and a dry feeling are persistent; even after consuming large quantities of water. Polyuria - excretion of very large quantities of urine (diluted). Urine output can range from 2.5 liters (2.6 quarts) per day to 15 liters (16 quarts) per day, compared to about 1.5 to 2.5 liters per day in other adults without the condition.

Patients may find that they need to pass pale, watery urine as often as every 15 to 20 minutes. This may make it very hard to be out of the house if there is no toilet nearby. In the UK patients may receive a toilet facility card which allows them to use toilets in non-public places.

The following signs and symptoms are also possible:

Nocturia - having to get up from sleep to urinate. Disrupted sleeping patterns can lead to fatigue (tiredness, irritability, and concentration problems. Enuresis - bed-wetting Feeling unwell - patients commonly feel run down for much of the time.

The following signs and symptoms may be present among young children with diabetes insipidus:

Cool hands and feet Delayed growth (failure to thrive) Diapers (UK: nappies) which are excessively wet Diarrhea Dry skin Fever Inconsolable crying Unexplained fussiness Vomiting Weight loss (failure to thrive)

Anybody who has excessive thirst and urination should see their doctor as soon as possible. DIAGNOSTIC TESTS: Because diabetes mellitus is more common and because diabetes mellitus and diabetes insipidus have similar symptoms, a health care provider may suspect that a patient with diabetes insipidus has diabetes mellitus. But testing should make the diagnosis clear. A doctor must determine which type of diabetes insipidus is involved before proper treatment can begin. Diagnosis is based on a series of tests, including urinalysis and a fluid deprivation test. Urinalysis is the physical and chemical examination of urine. The urine of a person with diabetes insipidus will be less concentrated. Therefore, the salt and waste concentrations are low and the amount of water excreted is high. A physician evaluates the concentration of urine by measuring how many particles are in a kilogram of water or by comparing the weight of the urine with an equal volume of distilled water.

A fluid deprivation test helps determine whether diabetes insipidus is caused by one of the following:

excessive intake of fluid a defect in ADH production a defect in the kidneys' response to ADH

This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary. In some patients, a magnetic resonance imaging (MRI) of the brain may be necessary as well. PATHOPHYSIOLOGY: ADH is the primary determinant of free water excretion in the body. Its main target is the kidney, where it acts by altering the water permeability of the cortical and medullary collecting tubules. Water is reabsorbed by osmotic equilibration with the hypertonic interstitium and returned to the systemic circulation. The actions of ADH are mediated through at least 2 receptors: V1 mediates vasoconstriction, enhancement of corticotrophin release, and renal prostaglandin synthesis; V2 mediates the antidiuretic response.[2, 3] Diminished or absent ADH can be the result of a defect in 1 or more sites involving the hypothalamic osmoreceptors, the supraoptic or paraventricular nuclei, or the supraopticohypophyseal tract. In contrast, lesions of the posterior pituitary rarely cause permanent diabetes insipidus, because ADH is produced in the hypothalamus and still can be secreted into the circulation. NURSING DIAGNOSES: Anxiety Deficient fluid volume Delayed growth & development Disabled family coping Energy field disturbance Fear Impaired oral mucous membrane Impaired urinary elimination Ineffective coping Risk for injury

NURSING MANAGEMENT: The patient with possible diabetes insipidus needs encouragement and support while undergoing studies for a possible cranial lesion. The nurse needs to inform the patient and family about follow-up care and emergency measures. The nurse also needs to

provide specific verbal and written instructions, show the patient how to administer medications, and observe return demonstrations as appropriate. The nurse also advises the patient to wear a medical identification bracelet and carry medications and informations about this disorder at all times. Vasopressin must be administered with caution if the patient has coronary artery disease because the medication causes vasoconstriction. MEDICAL MANAGEMENT: The objectives of the therapy are (1) to replace ADH (which is usually a long term therapeutic program), (2) to ensure adequate fluid replacement, and (3) to identify & correct the underlying intracranial pathology. Nephrogenic causes require different management approaches. PHARMACOLOGICAL MANAGEMENT: Treat diabetes insipidus (DI) with desmopressin, nonhormonal drugs, or both. In central DI, the primary problem is a hormone deficiency; therefore, physiologic replacement with desmopressin is usually effective. Use a nonhormonal drug if response is incomplete or desmopressin is too expensive. Nonhormonal drugs usually are more effective in treating nephrogenic DI. Hormones Hormones prevent complications of DI and reduce morbidity. Desmopressin (DDAVP) Desmopressin is a synthetic analogue of antidiuretic hormone (ADH)also known as arginine vasopressin (AVP)with potent antidiuretic activity but no vasopressor activity. Vasopressin (Pitressin) Vasopressin has vasopressor and ADH activity. It increases water resorption at collecting ducts (ADH effect) and promotes smooth muscle contraction throughout the vascular bed of renal tubular epithelium (vasopressor effects). However, vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels. Vasopressin decreases portal pressure in portal hypertension. A notable undesirable effect is coronary artery constriction, which may dispose patients with coronary artery disease to cardiac ischemia. This can be prevented with concurrent use of nitrates. Sulfonylurea Compounds Hypoglycemic agents help relieve diuresis.

Chlorpropamide Chlorpropamide promotes renal response to ADH. Anticonvulsants Certain antiepileptic drugs, such as carbamazepine, have proven helpful in DI. Carbamazepine (Tegretol, Carbatrol, Equetro) Carbamazepine ameliorates DI by releasing ADH. It is not useful in total DI and generally is not a first-line drug. Diuretics Diuretics may reduce flow to the ADH-sensitive distal nephron. Hydrochlorothiazide (Microzide) Hydrochlorothiazide is a thiazide diuretic that decreases urinary volume in the absence of ADH. It may induce mild volume depletion and cause proximal salt and water retention, thereby reducing flow to the ADH-sensitive distal nephron. Its effects are additive to those of other agents. Amiloride (Midamor) Amiloride is a potassium-sparing diuretic. It has a potassium-sparing effect, so the risk of hypokalemia is decreased in combination with hydrochlorothiazide. In addition, the 2 agents are synergistic with respect to antidiuresis. Nonsteroidal Anti-inflammatory Agents (NSAIDs) The mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) is not known, but these agents may act by inhibiting prostaglandin synthesis. Ibuprofen (Caldolor, Advil, Motrin) Inhibition of prostaglandin synthesis reduces the delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Ibuprofen is usually used in nephrogenic DI.

Indomethacin (Indocin) Inhibition of prostaglandin synthesis reduces the delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Indomethacin is usually used in nephrogenic DI.