CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0366/03662.txt

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$Unique_ID{BRK03662}
$Pretitle{}
$Title{Diabetes, Insipidus}
$Subject{Diabetes Insipidus Nephrogenic Diabetes Insipidus NDI
Vasopressin-resistant Diabetes Insipidus and Vasopressin-sensitive Diabetes
Insipidus Diabetes Insipidus Neurohypophyseal}
$Volume{}
$Log{}

Copyright (C) 1987, 1988, 1989, 1991, 1992, 1993 National Organization
for Rare Disorders, Inc.

335:
Diabetes, Insipidus

** IMPORTANT **
It is possible the main title of the article (Diabetes Insipidus) is not
the name you expected.  Please check the SYNONYMS listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Nephrogenic Diabetes Insipidus, also known as NDI, Vasopressin-resistant
     Diabetes Insipidus and Vasopressin-sensitive Diabetes Insipidus
     Diabetes Insipidus, Neurohypophyseal

General Discussion

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Diabetes Insipidus is due to an abnormality of anti-diuretic hormone
(vasopressin or ADH) originating in the posterior lobe of the pituitary
gland.  The lack of effect of this hormone on the kidney causes excretion of
excessive quantities of very dilute (but otherwise normal) urine.  Excessive
thirst is the major symptom of this disorder.

Symptoms

Nephrogenic Diabetes Insipidus (NDI), either the congenital or acquired type,
involves resistance by the kidney to the vasopressin hormone.

Neurohypophyseal Diabetes Insipidus involves absent or decreased
production or secretion of the vasopressin hormone by the pituitary gland.

Primary or idiopathic DI affects approximately fifty percent of those
with diabetes insipidus, and may be due to an inflammation of the pituitary
gland's posterior lobe (neurohypophyseal system).  The inherited form of
Diabetes Insipidus is extremely rare.  Secondary or acquired diabetes
insipidus can be due to a variety of pathologic lesions.

Onset of all types of Diabetes Insipidus may be abrupt and may occur at
any age.  The initial symptom is commonly excessive thirst.  Enormous
quantities of fluid may be ingested and excreted (3 to 30 liters/day).
Excessive urination at night (nocturia) usually occurs.  Loss of
consciousness may ensue if sufficient fluid is not retained in the body.
Some patients may also experience fever.

General health is usually good in cases of nephrogenic diabetes
insipidus, but some weakness may be experienced.  The constant need to drink
fluids may become a major nuisance to patients who can find it difficult to
live a normal life.

With cases of both Nephrogenic Diabetes Insipidus and Neurohypophyseal
Diabetes Insipidus, dehydration and resultant weakness, dryness of mouth
and/or skin, and constipation may develop rapidly if loss of fluid through
urine is not continuously replaced.

Brain damage with mental retardation may occur if the exact cause of
diabetes insipidus symptoms in infants is not speedily recognized.  Since an
infant cannot communicate thirst, severe dehydration with excessive amounts
of sodium in the blood (hypernatremia), fever, vomiting and/or convulsions
should be recognized as possible Diabetes Insipidus symptoms.

Causes

Nephrogenic Diabetes Insipidus (a genetic form of DI) is often inherited as
an X-linked trait.  It may also be autosomal dominant in other forms of the
disorder.

(Human traits including the classic genetic diseases, are the product of
the interaction of two genes for that condition, one received from the father
and one from the mother.

X-linked recessive disorders are conditions which are coded on the X
chromosome.  Females have two X chromosomes, but males have one X chromosome
and one Y chromosome.  Therefore in females, disease traits on the X
chromosome can be masked by the normal gene on the other X chromosome.  Since
males have only one X chromosome, if they inherit a gene for a disease
present on the X, it will be expressed.  Men with X-linked disorders transmit
the gene to all their daughters, who are carriers, but never to their sons.
Women who are carriers of an X-linked disorder have a fifty percent risk of
transmitting the carrier condition to their daughters, and a fifty percent
risk of transmitting the disease to their sons.)

In dominant disorders, a single copy of the disease gene (received from
either the mother or father) will be expressed "dominating" the normal gene
and resulting in appearance of the disease.  The risk of transmitting the
disorder from affected parent to offspring is 50% for each pregnancy
regardless of the sex of the resulting child.)

A partial form of the disorder may be confined to females who may be
genetic carriers but not show symptoms of the disorder.

Neurohypophyseal Diabetes Insipidus can be inherited either as an
autosomal dominant or X-linked trait (see above).  In other cases it may
occur spontaneously as a result of a lesion.  Any lesion, either congenital
or acquired, may damage the essential structure of the posterior lobe of the
pituitary gland (neurohypophyseal system) where the antidiuretic hormone
(vasopressin or ADH) is stored.  A lesion may be temporary when resulting
from trauma, but may last longer when due to other causes.

The acquired lesions which may produce DI (in decreasing order of
frequency) are:

     1) Pituitary gland surgery (posthypophysectomy).

     2) Cranial injuries, particularly basal skull fractures.

     3) Pituitary gland area tumors may originate in the pituitary gland
(primary) or be spread to the pituitary gland from another area
(metastatic).

     4) Histiocytosis, a cellular disorder of the connective tissue due to an
inflammation, can also cause DI.

     5) Granulomas (sarcoidosis or tuberculosis) can produce a mass or nodule
of tissue that can cause DI by destroying normal neurohypophyseal tissue.

     6) Vascular lesions may include a sac formed by dilatation of the wall
of an artery (aneurysm) or a type of blood clotting which causes an
obstruction in a vein (thrombosis) which may affect the blood supply of the
pituitary gland.

     7) Infections, such as encephalitis or meningitis, may affect the
pituitary gland.

Affected Population

The inherited forms of Diabetes Insipidus usually affect males.  Females can
be carriers of the genetic defect and can possibly pass it on to their
offspring.  It may begin at any age, usually rapidly and without warning.

In nephrogenic DI, the first symptoms may appear during infancy.  In
adults, dehydration and fever may accompany the abrupt onset.

In neurohypophyseal DI, which is rarer, onset usually occurs during
infancy or early childhood.  An abrupt onset may also occur in adults.

Related Disorders

Diabetes Mellitus (Insulin Dependent) is a more common disorder in which the
body does not produce enough insulin and is, therefore, unable to convert
nutrients into the energy necessary for daily activity.  The disorder is
genetic but environmental factors may play a role in determining which
genetically predisposed people will get the disorder.  More females than
males are affected by diabetes mellitus.  The most obvious symptom is
unusually excessive thirst.  (For more information on this disorder, choose
"Diabetes Mellitus) as your search term in the Rare Disease Database.)

For more information on diabetes, see the related articles in the
Prevalent Health Conditions/Concerns area of NORD Services (rdb-4).

Therapies:  Standard

1)  HORMONE THERAPY
     Hormone therapy may be beneficial to people with Diabetes Insipidus.  If
a lesion is found it may be eradicated in some cases.  Otherwise, effective
control of DI may be obtained with several preparations of the vasopressin
hormone (ADH) which are commercially available.  These include Lypressin (a
synthetic vasopressin as a nasal spray which is the simplest form for self
administration) and Desmopressin Acetate (a longer acting synthetic ADH
substitute).  Both of these drugs may be inhaled or blown high into the nasal
passages with an insufflator.  In many patients nasal irritation may be a
limiting factor with this form of treatment.

Intramuscular injections of vasopressin tannate in (pitressin tannate)
was the mainstay of the treatment for diabetes insipidus until 1990 when
manufacture of this product by Parke Davis ceased due to manufacturing
difficulties.

An aqueous posterior pituitary hormone injection has little use in
chronic treatment of Diabetes Insipidus, but an intramuscular injection may
give an antidiuretic response lasting usually six hours or less.

2) NON-HORMONAL THERAPY
     Two types of drugs have been found useful in reducing excessive
urination.  These include various diuretics (primarily thiazides), and the
ADH releasing drugs (including chlorpropamide, carbamazepine and clofibrate).
These drugs paradoxically reduce urine volume by reducing extracellular fluid
volume while increasing use of the natural vasopressin hormone.  These drugs
may reduce or eliminate the need for vasopressin in some patients.

Hypoglycemia may be a significant adverse reaction to Chlorpropamide
therapy.  If this occurs, partial or total substitution with Clofibrate or
Carbamazepine is sometimes suggested.  Because the effects of these three
drugs differ from those of the thiazides, the use of one of these agents with
a diuretic may show additive effects and be of benefit to some patients.

Desmopressin Acetate (DDAVP) nasal spray was approved by the FDA as a
treatment for Diabetes Insipidus in 1989.  This drug appears to offer
enhanced antidiuretic activity with minimal adverse effects on the vascular
system or smooth muscles.  DDAVP is manufactured by:

     Rorer Group Inc.
     500 Virginia Dr.
     Fort Washington, PA  19034

A laboratory test is now available to determine if Diabetes Insipidus is
the inherited form of he disease (nephrogenic diabetes insipidus) and to
identify women who may be carriers of the disease.

Therapies:  Investigational

Research in treating Diabetes Insipidus is ongoing.  Prostraglandin synthesis
inhibitors under investigation have not shown uniform effectiveness in
patient therapy.  Use of the orphan drug hydrochlorothiazide-amiloride in the
treatment of congenital nephrogenic diabetes insipidus has indicated that
treatment with both of these compounds may possibly be more effective than
hydrochlorothiazide alone, and can be a satisfactory alternative to the
hydrochlorothiazide-prostaglandin synthetase inhibitor combination in the
treatment of nephrogenic DI.

Clinical trials are underway to study the genetic basis of familial
neurogenic Diabetes Insipidus.  Interested persons may wish to contact:

     Dr. Gary L. Robertson
     Northwestern Memorial Hospital
     250 E. Superior St., Rm. 1625
     Chicago, IL  60611
     [phone]

to see if further patients are needed for this research.

This disease entry is based upon medical information available through
April 1993.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Diabetes Insipidus, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Diabetes Insipidus & Related Disorders Network
     RT #2, Box 198
     c/o Beth Perry
     Creston, IA  50801
     [phone]

     American Diabetes Association
     National Service Center
     1660 Duke Street
     Alexandria, VA  22314
     [phone]
     (800) ADA-DISC (232-3472)

     National Diabetes Information Clearinghouse
     Box NDIC
     Bethesda, MD  20892
     [phone]

For information on genetics and genetic counseling referrals, please
contact:

     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

TREATMENT OF NEPHROGENIC DIABETES INSIPIDUS WITH PROSTAGLANDIN SYNTHESIS
INHIBITORS:  S. Libber, et. al., eds.;  J Pediatr (Feb. 1986 issue 108(2).
Pp. 305-311.

HYDROCHLOROTHIAZIDE-AMILORIDE IN THE TREATMENT OF CONGENITAL NEPHROGENIC
DIABETES INSIPIDUS:  V. Alon and J.C. Chan;  Am J Nephrol  (1985, 51).  Pp.
9-13.