CDI is caused by partial or complete deficiency of the antidiuretic hormone, arginine vasopressin. This deficiency usually results from damage to the hypothalamus or pituitary gland. In extremely rare cases, vasopressin deficiency is caused by a genetic mutation that is inherited as an autosomal dominant or autosomal recessive trait. In approximately one third of cases, no specific cause can be identified (idiopathic) and may be autoimmune in etiology.
The hypothalamus is a portion of the brain that acts as a link between the brain and the endocrine systems. The hypothalamus releases neuro-hormones that influence the secretion of other hormones such as those that aid in the regulation of various metabolic process, growth, reproductive function and autonomic functions of the body. One of the substances secreted by the hypothalamus is vasopressin, which travels via nerve fibers to the posterior pituitary gland.
The pituitary is a small gland located near the base of the brain that stores several hormones and releases them into the bloodstream as needed by the body. These hormones regulate many bodily functions. The posterior lobe of the pituitary gland is known as the neurophysis (neurohypophsyeal region), which stores hormones and eventually secretes them into the bloodstream. After the hypothalamus produces vasopressin, the hormone travels to the pituitary gland, and is stored in the neurophysis. Vasopressin is eventually released into the bloodstream as needed by the body. Vasopressin travels to the kidneys where it binds to receptor proteins found on the surface of certain kidney cells, initiating a process through which the kidneys reabsorb water into the body. Without proper levels of vasopressin, water is not reabsorbed and is lost through urination.
Damage to the hypothalamus, pituitary gland or the connection between the hypothalamus and pituitary gland (pituitary stalk) may impair the production, transport, storage, or release of vasopressin, which in turn impairs the ability of the body to conserve water. Such damage may occur from trauma due to an accident or surgery (e.g., surgery to remove a tumor in the area), various infections, tumors such as a craniopharyngioma or a germinoma, a rare disease known as Langerhans cell histiocytosis, or a variety of inflammatory, vascular, or granulomatous diseases.
In rare cases, CDI may be inherited as an autosomal dominant trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. Even rarer is an autosomal recessive mode of inheritance in which neither parent is affected but each carries an abnormal gene which when combined together in the offspring result in disease.
Investigators have determined that some cases of inherited CDI are caused by disruptions or changes (mutations) of the arginine vasopressin (AVP) gene. Mutations of the AVP gene impair the production (synthesis) or secretion of vasopressin.
The AVP gene is located on the short arm (p) of chromosome 20 (20p13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Researchers believe that some cases of idiopathic CDI may be caused by autoimmune factors. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons. In CDI, the body produces antibodies or lymphocytes that attack cells that secrete vasopressin.
CDI may also occur as part of a larger syndrome or disorder including Wolfram syndrome or septo-optic dysplasia. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)