Monday, June 25, 2012

What Is Diabetes Insipidus? What Causes Diabetes Insipidus?

Diabetes insipidus is a condition in which the body cannot retain enough water. The patient is excessively thirsty and excretes large amounts of extremely diluted urine - a reduction in fluid intake does not reduce amounts and consistency of urine excretion. It is a rare condition, affecting approximately 1 in every 25,000 people.

Diabetes insipidus is not related to diabetes mellitus (sugar diabetes). The term diabetes on its own nearly always refers to diabetes mellitus. This article is about diabetes insipidus - the condition characterized by intense thirst and polyuria (excretion of large amounts of urine).

In most cases diabetes insipidus occurs because the body does not properly produce, store or release a key hormone - arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). It may also occur when the kidneys do not respond properly to ADH (antidiuretic hormone).

There are three types of diabetes insipidus:
  • Neurogenic diabetes insipidus - a deficiency with ADH (antidiuretic hormone).
  • Nephrogenic diabetes insipidus - insensitivity of the kidneys to ADH.
  • Gestational diabetes insipidus - in very rare cases diabetes insipidus may also occur during pregnancy.
According to Medilexicon's medical dictionary:
    Diabetes insipidus is "Chronic excretion of very large amounts of pale urine of low specific gravity, causing dehydration and extreme thirst; ordinarily results from inadequate output of pituitary antidiuretic hormone; the urine abnormalities may be mimicked as a result of excessive fluid intake, as in psychogenic polydipsia. Two types exist: central and nephrogenic. Autosomal dominant [MIM*125700, *125800, *192340], X-linked [MIM*304800 and *304900], and even autosomal recessive forms [MIM*222000] have been described."

What are the signs and symptoms of diabetes insipidus?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

The main signs and symptoms of diabetes insipidus include:
  • Extreme thirst - patients find themselves having to drink water all the time. The constant thirst and a dry feeling are persistent; even after consuming large quantities of water.
  • Polyuria - excretion of very large quantities of urine (diluted). Urine output can range from 2.5 liters (2.6 quarts) per day to 15 liters (16 quarts) per day, compared to about 1.5 to 2.5 liters per day in other adults without the condition.

    Patients may find that they need to pass pale, watery urine as often as every 15 to 20 minutes. This may make it very hard to be out of the house if there is no toilet nearby. In the UK patients may receive a toilet facility card which allows them to use toilets in non-public places.
The following signs and symptoms are also possible:
  • Nocturia - having to get up from sleep to urinate. Disrupted sleeping patterns can lead to fatigue (tiredness, irritability, and concentration problems.
  • Enuresis - bed-wetting
  • Feeling unwell - patients commonly feel run down for much of the time.
The following signs and symptoms may be present among young children with diabetes insipidus:
  • Cool hands and feet
  • Delayed growth (failure to thrive)
  • Diapers (UK: nappies) which are excessively wet
  • Diarrhea
  • Dry skin
  • Fever
  • Inconsolable crying
  • Unexplained fussiness
  • Vomiting
  • Weight loss (failure to thrive)
Anybody who has excessive thirst and urination should see their doctor as soon as possible.

What are the causes of diabetes insipidus?

Our kidneys remove excess body fluids from our bloodstream. This excess fluid waste is stored as urine in the bladder. If our body fluid levels drop due to, for example perspiration (sweating), our kidneys produce less urine in order to maintain a proper body fluid level balance.

Our fluid volume and composition remains balanced through a combination of fluid consumption and excretion in the kidneys. The amount we consume is mainly dictated by our thirst, even though individual habits may result in consuming more than we need. Our fluid excretion rate (through our kidneys) is influenced significantly by the production of ADH (anti-diuretic hormone), also known as vasopressin.

ADH is produced in the hypothalamus (a gland in the brain that also controls processes in the body, such as mood and appetite) and is stored in the pituitary gland (found just below the brain, behind the bridge of the nose). ADH is released into the bloodstream whenever it is needed. ADH also makes the kidney tubules reabsorb water back into the bloodstream - concentrating the urine.

Diabetes insipidus occurs when something goes wrong with this system and the body is unable to properly regulate body fluid levels. There are different types of diabetes insipidus:
  • Central diabetes insipidus (cranial diabetes insipidus) - usually caused by damage to the hypothalamus or the pituitary gland, often as a result of surgery, a tumor, meningitis, inflammation or a head injury, which disrupts ADH production, storage and release. Central diabetes insipidus that is caused by a head injury, or surgery to your pituitary gland, is sometimes only a temporary condition that lasts for just a couple of weeks. On some occasions the exact cause is never determined.
  • Nephrogenic diabetes insipidus - there is something wrong with the kidney tubules. The tubules cause fluids to be excreted or reabsorbed. Patients' kidneys do not respond properly to ADH. This may be caused by a congenital problem (inherited disorder) or some chronic (long-term) kidney disorder. Lithium, tetracycline and some other medications may also cause nephrogenic diabetes insipidus.
  • Gestational diabetes insipidus - occurs during pregnancy. An enzyme produced by the placenta may destroy AHD in the mother.

Diagnosing diabetes insipidus

A GP (general practitioner, primary care physician) will ask the patient about symptoms and recommend some tests. An endocrinologist - a doctor who specializes in hormone conditions - will carry out the tests.

Some of the signs and symptoms of diabetes insipidus are present in other conditions, including diabetes mellitus. If diabetes insipidus is diagnosed, the doctor will also have to determine which type it is, as treatment options will be different for each form of the disease. The following tests may be ordered:
  • Water deprivation test - the patient stops drinking liquids for two to three hours before starting the test so that the doctor may measure alterations in body weight, and urine output and composition. Sometimes blood levels of ADH may also be measured. If the patient has diabetes insipidus they will continue passing large amounts of diluted urine, compared to other people who would pass only a small amount of concentrated urine.

    This test also helps the doctor determine which form of diabetes insipidus the patient has. Pregnant women and children have to be monitored very closely during this test to make sure they do not lose more than 5% of body weight.
  • Urine test - a urinalysis examines the physical chemical content of urine. If urine water content is high and salt and waste concentrations are low, it may mean the patient has diabetes insipidus. If a large amount of sugar is found in the patient's urine, they may have diabetes mellitus rather than diabetes insipidus.
  • MRI (magnetic resonance imaging) scan - the doctor may wish to observe the pituitary gland or hypothalamus areas for any abnormalities. If any abnormality is found, such as a tumor, this will need to be treated first.
  • ADH (antidiuretic hormone) test - after the water deprivation test the doctor may give a small dose of ADH, usually in the form of an injection. This test shows how the patient reacts to the hormone, and can help determine which form of diabetes insipidus the patient has. If the ADH dosage stops the patient from producing urine, most likely their condition is caused by a shortage of ADH, and they will be diagnosed with central diabetes insipidus. If, on the other hand, the patient continues to produce excess urine despite the ADH dose, it probably means that the patient has nephrogenic diabetes insipidus (the kidneys are not responding to ADH).
The doctor may ask the patient whether any relatives have (had) excessive urination (polyuria). Genetic screening may be recommended if an inherited form of the disease is suspected.

What are the treatment options for diabetes insipidus?

Treatment depends on the type of diabetes insipidus the patient has.

Treatment for central (cranial) diabetes insipidus - if the patient's symptoms are mild; producing three to four liters of urine per 24-hour period, no medical treatment may be needed. In such mild cases the patient will be asked to increase their fluid intake in order prevent dehydration.

In more severe cases - when just consuming more water is not enough - the patient may be given desmopressin.
    Desmopressin - this is a man-made, more powerful version of ADH. Desmopressin, like ADH, stops the kidneys from producing urine when the body's water level is low. Desmopressin may be taken as a nasal spray or in tablet form. The nasal spray (Desmospray or DDAVP) is usually administered twice a day, while the tablets are taken more frequently. If the patient develops a cold or some condition which makes it more difficult to effectively use the nasal spray, they may have to switch to tablets.

    Desmopressin is safe to use and has very few side effects. If the patient takes too much desmopressin, or consumes too much water there is a risk the body may retain too much water, resulting in headaches, dizziness, a bloated feeling, and hyponatremia (excessively low levels of sodium in the blood). Hyponatremia can lead to drowsiness, confusion, and even coma. So, it is important to stay within the recommended desmopressin dosage, and to only drink fluids when thirsty.

    The patient will need to have follow-up checks to make sure blood sodium levels are OK.
Treatment for nephrogenic diabetes insipidus - if caused by taking lithium, tetracycline or some other medication, the doctor will recommend an alternative medication. It is important not to stop taking medications unless the doctor says so.

Desmopressin is not used for the treatment of nephrogenic diabetes insipidus. Patients will be encouraged to consume plenty of fluids.

If the condition is mild the doctor may recommend a diet which is very low in protein and salt, so that the kidneys produce less urine. Only embark on a new diet if the doctor tells you to.

In more severe cases that patient may be given a diuretic called hydrochlorothiazide. Although hydrochlorothiazide makes most people produce more urine, it has the opposite effect if the patient has nephrogenic diabetes insipidus.

Treatment for gestational diabetes insipidus - the patient is given desmopressin. In some very rare cases the gestational diabetes insipidus is caused by an abnormality in the thirst mechanism. In such cases the patient is not given desmopressin.

What are the possible complications of diabetes insipidus?

Complications may occur if the condition is either undiagnosed or not well controlled.

Dehydration - patients may find it more difficult to retain enough water in the body, resulting in dehydration. Dehydration may occur even if the patient drinks a lot of fluids. The following signs and symptoms may mean the patient with diabetes insipidus is dehydrated:
  • Dry mouth
  • Dry lips
  • Headaches
  • Confusion
  • Irritability
  • Dizziness
If the individual is very dehydrated it is better to consume re-hydration fluids, instead of just water. Rehydration fluids replace lost minerals, salts, sugars - as well as lost fluids. In very severe cases the patient may need to be hospitalized and given fluids through a drip into a vein (intravenously).

Electrolyte imbalance - diabetes insipidus can also cause an electrolyte imbalance. In our bodies, electrolytes include sodium (Na+), potassium (K+), calcium (Ca2+), bicarbonate (HCO3-, magnesium (Mg2+), chloride (C1-), hydrogen phosphate (HPO42-), and hydrogen carbonate (HCO3-). Electrolytes regulate our nerve and muscle function, our body's hydration, blood pH, blood pressure, the rebuilding of damaged tissue. Various mechanisms exist in our body that keep the concentrations of different electrolytes under strict control.

Our muscles and neurons are thought of as electric tissues of the body. They are activated by electrolyte activity between extracellular fluid or interstitial fluid, and intracellular fluid (fluid inside and outside or between cells).

A muscle contraction needs calcium (Ca2+), sodium (Na+) and potassium (K+) to be present. If levels of vital electrolytes are wrong, the muscles either become too weak, or their contractions are too severe. Our heart, muscle and nerve cells use electrolytes to maintain voltages across their cell membranes to carry electrical impulses across themselves and to other cells.

The level of an electrolyte in the blood can become too high or too low. Body electrolyte levels tend to change when water levels in the body change - when our level of hydration is altered.

An electrolyte imbalance can lead to several symptoms. The symptoms will depend on which electrolyte is out of balance, and whether that level is too high or low. An altered level of magnesium, sodium, potassium, or calcium may produce one or more of the following symptoms:
  • Weakness
  • Twitching
  • Seizures
  • Numbness
  • Nervous system disorders
  • Muscle spasm
  • Fatigue, lethargy
  • Irregular heartbeat
  • Convulsions
  • Confusion
  • Bone disorders
  • Blood pressure changes
An electrolyte imbalance is treated in the same was as dehydration, with fluids that contain electrolytes.

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