Diabetes insipidus
Diabetes insipidus (DI) is a condition characterized by the body's inability to properly regulate fluid balance, leading to excessive thirst and the excretion of large volumes of dilute urine. There are two main forms of diabetes insipidus: central DI, which arises from a deficiency of antidiuretic hormone (ADH) due to issues in the hypothalamus, and nephrogenic DI, where the kidneys do not respond appropriately to ADH. Various risk factors can predispose individuals to develop DI, including damage to the hypothalamus, certain kidney diseases, and the use of specific medications.
Symptoms of diabetes insipidus may include extreme thirst, frequent urination, dehydration, and related complications. Diagnosis typically involves medical history assessments, physical examinations, and laboratory tests to evaluate urine concentration and ADH levels. Treatment approaches may differ for central and nephrogenic DI, with options ranging from synthetic ADH to diuretics and dietary changes. While there are no known prevention methods for DI, early medical intervention is crucial for managing symptoms and improving quality of life.
Diabetes insipidus
DEFINITION: There are two forms of diabetes insipidus (DI). Central diabetes insipidus (central DI) is caused by inadequate antidiuretic hormone (ADH). Nephrogenic diabetes insipidus (NDI) is due to renal cells in the kidneys that do not respond to ADH.
Risk Factors
Among the factors that increase an individual’s chance of developing insipidus are damage to the hypothalamus due to surgery, infection, tumor, or head injury; having polycystic kidney disease or another kidney disease that may affect the filtration process; and the use of certain medications, such as lithium, amphotericin B, or demeclocycline. Other risk factors include having high blood levels of calcium and low blood levels of potassium.
Etiology and Genetics
Nephrogenic diabetes insipidus can be either inherited or acquired. In cases of inherited disease, mutations in either of two different genes may be responsible. The great majority of inherited cases (perhaps as many as 90 percent) result from mutations in a gene called AVPR2, found on the long arm of the X chromosome at position Xq28. The product of this gene is the arginine vasopressin receptor-2 protein, and its normal function is to recognize and bind antidiuretic hormone in the kidneys. When the gene is mutated, the altered protein fails to respond to the hormone, and normal fluid balance regulation in the kidneys is disrupted. The inheritance pattern of this form of the disease is typical of all sex-linked recessive mutations (those found on the X chromosome). Mothers who carry the mutated gene on one of their two X chromosomes face a 50 percent chance of transmitting this disorder to each of their male children. Female children have a 50 percent chance of inheriting the gene and becoming carriers like their mothers. Although females rarely express the condition fully, female carriers may occasionally show minor manifestations. Affected males will pass the mutation on to all of their daughters but to none of their sons.
Mutations in a different gene, AQP2, are responsible for the remaining 10 percent of cases of inherited diabetes insipidus. Located on the long arm of chromosome 12 at position 12q13, this gene encodes a protein known as aquaporin-2, which is a pore-forming protein that permits the passage of water through the plasma membranes of certain kidney cells. It normally functions to reabsorb water from the urine, but mutations in the gene can result in an inactive pore protein that absorbs too little water, yielding an abundance of dilute urine and resulting dehydration. This form of the disease is inherited as an autosomal recessive, meaning that both copies of the APQ2 gene must be deficient in order for the individual to be afflicted. Typically, an affected child is born to two unaffected parents, both of whom are carriers of the recessive mutant allele. The probable outcomes for children whose parents are both carriers are 75 percent unaffected and 25 percent affected. If one parent has diabetes insipidus of this type and the other is a carrier, there is a 50 percent probability that each child will be affected.
Symptoms
Individuals who have any of the symptoms of diabetes insipidus should not assume that it is due to the disease. These symptoms may be caused by other health conditions. Individuals should see their doctors if they experience any one of the symptoms. Extreme thirst with preference for cold drinks is a symptom of central DI. Other symptoms of diabetes insipidus include muscle weakness; headache; fever; blurred vision; low blood pressure; rapid pulse; frequent urination, especially during the night (nocturia); and dehydration.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history. A physical exam may be done. Tests may include blood tests to check for electrolytes, ADH levels, or blood sugar. Urinalysis tests the urine specific gravity and/or osmolality (which measures how concentrated or dilute the urine is). A water deprivation test is done only under a doctor’s supervision and measures urine output for a twenty-four-hour period. Diabetes insipidus can cause as much as 4 to 10 liters of urine to be excreted per day. In central DI, urine output is suppressed by a dose of vasopressin/ADH; in NDI, urine output is not suppressed by a dose of vasopressin/ADH. Other tests include a magnetic resonance imaging (MRI) scan of the head if central DI is suspected.
Treatment and Therapy
Individuals should talk with their doctors about the best plans for them. Treatment options for central DI include a synthetic form of ADH called demo; this drug can be taken by mouth, inhaled through the nose, or injected. A diuretic “water pill” or an antidiabetic medication may also be taken in mild cases to boost the ADH effect on the renal cells in the kidney.
A diuretic “water pill” can be used to treat NDI. If lithium is causing the problem, another diuretic, amiloride, can be used. It can also sometimes be resolved by balancing calcium or potassium levels in the body. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be prescribed to treat NDI as well.
In both central DI and NDI, symptoms can often be reduced by decreasing the amount of sodium in the diet and by medications called thiazide diuretics (diuretics that conserve water loss and decrease urine output in people with diabetes insipidus).
Prevention and Outcomes
There are no known ways to prevent diabetes insipidus. It is wise for patients to seek medical attention promptly if they have excessive urination and thirst.
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