$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 (312) 503-0058 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 (203) 746-6518 Diabetes Insipidus & Related Disorders Network RT #2, Box 198 c/o Beth Perry Creston, IA 50801 (515) 782-7838 American Diabetes Association National Service Center 1660 Duke Street Alexandria, VA 22314 (703) 549-1000 (800) ADA-DISC (232-3472) National Diabetes Information Clearinghouse Box NDIC Bethesda, MD 20892 (301) 468-2162 For information on genetics and genetic counseling referrals, please contact: 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 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.