Diabetes Insipidus 
 Kathy Clark
RN CS MSN Pediatric Nurse Practitioner     

Altered Antidiuretic Hormone Function: Posterior Pituitary Dysfunction DIABETES INSIPIDUS

DEFINITION AND INCIDENCE
Diabetes insipidus (DI) is the result of the deficiency in hormone antidiuretic (ADH), sometimes called vasopressin. Because the kidneys depend on ADH to concentrate urine appropriately, the lack of ADH leads to massive renal loss of fluids.

DI is also called neurogenic DI and must be differentiated from psychogenic water drinking. This condition mimics DI in the excessive amount of urine the child produces, but these children do not have an abnormality of ADH production. Children with psychogenic water drinking produce copious amounts of urine in response to the excessive quantity of fluids ingested. In DI, the child drinks copious amounts of fluid to replace the excessive loss of fluid though urine. Neither neurogenic DI nor psychogenic water drinking should be confused with nephrogenic DI, a rare, inherited disorder in which the renal tubes are unresponsive to ADH.

ETIOLOGY AND PATHOPHYSIOLOGY
ADH works directly on the renal collecting ducts and the distal tubules, to increase membrane permeability for water and urea. A deficiency in ADH allows water to diffuse into the urine. Decreased ADH secretion promotes massive water loss and retention of sodium in the serum. Damage to the

posterior pituitary gland may injure the cells responsible for the production of ADH. DI can be seen in conjunction with other hyothalamic-pituitary hormone deficiencies. It also can occur as an autosomal recessive deficiency, or the cause may be unknown. This condition can occur at any age.

Some children with DI have damage to the thirst center in the hypothalamus. These children rapidly become gravely ill, because their diuresis is not balanced by the drive to drink fluids to replace the loss. This rare situation is the severest from of the disorder and is characterized by a fragile balance in life.

CLINICAL MANIFESTATIONS
In psychogenic water drinking, excessive drinking habits are established over a long period. In contrast, the sudden onset of excessive thirst and polyuria are classic manifestations of DI. Frequent, abrupt trips to the bathroom are typical, with noturia and enuresis suddenly occurring in the child who previously had gained night-time bladder control. The child awakens because of thirst at night.

Parents often state that their child will suddenly run to the bathroom to urinate, then stop to drink two or three glasses of water. Children prefer water to all other beverages, infants reject formula or breast milk in their desire for water. The thirst may be so intense that the child cannot eat sufficient calories to gain weight and grow.

The child's urine is extremely dilute and often colorless. The child may show signs of mild dehydration, such as sunken fontanel in the infant, poor skin turgor, and dry mucous membranes, despite an enormous fluid intake. If the cycle of urine loss and abnormal drinking continues unchecked, the kidneys and bladder may begin to dilate to accommodate the large quantities of fluids that are ingested.

DIAGNOSTIC STUDIES
In the otherwise healthy child, the evaluation for DI has two steps:

1. to discover whether the excessive urination and drinking are due to ADH deficiency, and if so,
2. to determine the cause of this problem. If the child has a known organic illness that is associated with pituitary malfunction, the diagnosis of DI is made more easily.

Initial screening tests include urine and serum specimens. Electrolytes, blood urea nitrogen, and creatineine levels are evaluated to screen for kidney disease. The sodium and osmolality of both urine and serum are analyzed and compared, and the specific gravity of the urine is analyzed. In DI, dilute urine is present although the serum is very concentrated and sodium is elevated. Children with psychogenic water drinking may have dilute urine, but the serum also is dilute and sodium is low. In nephrogenic DI, this screening test mimics true DI. Serum measurement
for ADH is recommended is recommended as the most reliable diagnostic tool in conjunction with plasma osmolality.

When DI is suspected the child is hospitalized for water deprivation test, which is potentially dangerous and requires close monitoring. Fluids are withheld and the urine volume and concentration are monitored. This test differentiates psychogenic water drinking and neurogenic or nephrogenic DI.

The water deprivation test is generally followed by a test dose of ADH, usually administered as a nasal spray of short-acting DDAVP. A dose of this medication stops the abnormal diuresis that occurs in DI and results in
cessation of the symptoms. DDAVP does not stop the diuresis associated with nephrogenic DI.

An MRI or CT scan of the hypothalamic-pituitary region is done in children when the cause of DI is not known. A renal ultrasound is recommended when the condition has been long-standing to determine the extent of dilation of the renal system due to excessive urine volume and urination interrupt the child's life; choices of fluids, such as carbonated beverages or juices rather than water, drinking from unusual sources such as toilet bowls and dog dishes; the parent-child interaction, and peer and school problems.

Part 2 of Diabetes Insipidus.......called DI and ADH is the antidiuretic hormone and DDAVP is a desmopressin.

HORMONE REPLACEMENT
Most children with DI need daily replacement of vasopressin (ADH) using desmopressin (DDAVP), a synthetic analogue of ADH. Affected children usually have an intact thirst mechanism and need free access to water. DDAVP works through absorption in the highly vascularized nasal mucosa. It is available as a metered nasal spray (used largely in adults), a measured insufflation (nasal) tube which is primarily used in children , or an intramuscular injection. DDAVP has immediate action and lasts between 8 and 24 hours. DDAVP prevents diuresis only when the kidney is healthy.

Initial dose adjustment and education occur during the hospital stay. Careful monitoring of the child's response to treatment is necessary; evidence of adequate treatment includes daily weight gain, electrolyte balance, ability to return to normal voiding,and drinking patterns, and the ability to concentrate urine.

Administration of DDAVP is a skill that requires practice and a cooperative child or an extra adult. The insufflation tubing generally is used for children because the metered spray delivers a large dose (0.1mg per spray). Most children require one or two doses daily, at bedtime and in the morning. The dose is response-based and ranges from 0.05 to 0.2 ml per day.

In infants and younger children, the volume required may be so small that it cannot be properly measured in the insufflation tubing. An accurate measuring device can be constructed by cutting off the needle of a butterfly infusion set and attaching the thin tubing to a tuberculin syringe. Administration of the dose while the infant is asleep is advised to avoid the conflict that results when the nares are entered.

Children may swallow the dose instead of inhaling it when the volume is too great or their nasal surface area is too small. However DDAVP is not absorbed in the oral cavity, the esophagus or the stomach. When swallowing is detected the caregiver should split the dose and give half in each nare. Liquid DDAVP may also be given sublingually (under the tongue), but the required dose is much higher.

DDAVP is a costly medication nevertheless, an extra bottle should be kept at home in reserve. Care must be taken to protect it from heat; refrigeration is recommended.

All children on DDAVP should have their dose adjusted to allow a daily period of "breakthrough" when symptoms are permitted to develop. Breakthrough is evidenced by a sudden desire to use the bathroom, followed by a trip to the kitchen sink for a few glasses of water. Most children experience breakthrough after school or in the evening when they are at home and can freely drink and urinate. When the child returns home after the initial hospitalization, the parents are instructed to call the health care provider if this breakthrough fails to occur.

GENERAL GUIDELINES

• Refrigerate the medication, and keep out of heat.
• Keep medication cool in an insulated thermos when traveling.
• Have an extra bottle of DDAVP at home in case of breakage, spillage, or overheating.
• Discard the medication if the medication is overheated (when several doses do not provide adequate coverage).
• Establish a single pharmacy for obtaining the medication.
• Do not repeat doses that might have been swallowed or poorly absorbed. (Overdosing is a serious medical emergency.)

INFANTS AND YOUNGER CHILDREN

• Use the measuring device as ordered by the physician
• Administer the medication while the child is asleep to avoid conflict.
• Split the dose, and give one in each nare if the child is swallowing the medication.
• Clear the nostrils of a child with a respiratory infection before giving this medication

ADMINISTRATION

• Insert the tube into the bottle.
• Fill up the tube to the proper dosage line.
• Hold the top of the tube closed.
• Insert the medication-filled end into the nare.
• Blow the liquid out of the tubing and into the nares.

FLUID ADJUSTMENT AT HOME
Parents are educated to note drinking patterns at home and report any changes. For example, the child ,may prefer to drink rather than to eat. One or two days of increased drinking and urination are seldom cause for concern, but pattern of changed behavior needs to be evaluated. Free access to fluids is essential for children with deficient ADH. The preferred and recommended fluid is water. For children who are underweight, caloric beverages, such as milk and juices, should be encouraged. During increased physical activity or in hot weather, adequate replacement fluid must be provided for insensible water loss. Determination of urine specific gravity at home rarely is needed for children. However, it can be done through the use of a refactometer or urine dipsticks. These techniques can be taught to families during the initial hospitalization. Infants with DI are weighed daily at home, and specific gravity is checked when they are ill or when weight gain is poor. They are fed every 2 hours and are offered water in addition to breast milk or formula. Parents are encouraged to keep a diary that documents the number of wet diapers and feedings during the adjustment period.

TEACHING AND COUNSELING
Children and parents should be provided education concerning lifestyle needs and changes that take place after diagnosis. Children may desire that their teacher be given explanation about the the child's possible need to use the drinking fountain and bathroom more frequently than other children. Gym teachers and coaches must be told of the need for extra fluids and access to the bathroom. Some children increase their dose of DDAVP on the day that they plan to have a field trip or sports event. This is a safe practice if the child has and intact thirst center and has the physician's approval. All children should be encouraged to wear medical alert tags stating that they have DI.

COMPENSATED DI
In milder cases of DI, children with intact thirst centers can manage to maintain water balance without medication, by drinking enough fluids to offset fluid loss in urination. These children need to be monitored carefully to prevent kidney and bladder dilation. They may choose to use DDAVP when traveling or at night.

CARE OF CHILDREN LACKING A THIRST CENTER
Children who lack a thirst center require much more careful monitoring at home. They must be encouraged to drink at each meal and between meals. Children who resist drinking are tube fed to provide the water needed. Their fluid replacement needs are individually calculated during the hospitalization. Daily weights, urine specific gravity measurement, and intake and output at home may be required.

COMPLICATIONS
Some children adapt to polyuria (increased urine) and polydipsia (increased thirst) and do not seek adjustment of their medication as they grow. Long term mismanagement of DI, however can result in bladder, kidney, and pelvic damage, and central nervous system damage, vascular changes, and dehydration can occur. Children requiring IV therapy must be monitored closely due to the high risk for fluid overload. Weight gain occurs as fluids are retained and the child becomes weak and lethargic. The child may appear bloated. Anorexia, nausea, and vomiting develop as fluid and electrolyte balance deteriorates. The child eventually has confusion, convulsions, and coma. Fluid overload is considered life threatening. The goals for treatment are to reduce the fluid overload and raise the serum sodium level and osmolarity. Fluids are immediately restricted, and IVs reduced to keep-open-rate. Fluid overload is a temporary crisis and there should be no further risks to the child once the problem is corrected. Many children with DI have multiple hormone deficiencies and complex health care needs. They are followed by a pediatric endocrinologist.