Diabetes insipidus (DI), also now known as Arginine Vasopressin Deficiency (AVP-D), is a rare disorder that can occur as a consequence of histiocytosis involving the pituitary gland.
It should not be confused with the more common diabetes mellitus, also known as sugar diabetes, which results from too much sugar in the blood. Although both disorders have similar symptoms, in every other way including the cause and treatment, they are completely unrelated diseases.
The rate of occurrence for DI or AVP-D is not known, because there has been no organized method to count the number of patients. Some patients will present the symptoms of DI or AVP-D before receiving a diagnosis of histiocytosis, so communication with your physician about the possible connection between Diabetes Insipidus and histiocytosis, or other conditions, should be discussed.
Diabetes insipidus is a result of damage to the pituitary gland, a small gland at the base of the brain which stores and releases a hormone called ADH (antidiuretic hormone), also known as vasopressin. This hormone normally causes the kidney to control the amount of water released as urine from the body. When the pituitary is damaged, the kidneys lose too much water (increased urination), which then leads to increased thirst.
The connection between histiocytosis and diabetes insipidus was first reported in the late 1800s. Since then, DI has been recognized as a characteristic feature of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD). It is known to also occur in other histiocytic disorders, such as Rosai Dorfman disease (RDD) and Xanthogranuloma (XG/JXG).
It is believed that approximately between 5% and 50% of patients develop DI depending on the extent of disease. The risk of developing DI in patients with multisystem LCH is 4 to 6 times more than those with single-system disease. Patients with skull, facial, and/or eye bone lesions are at much higher risk of developing DI. This risk is increased further if the histiocytic disorder remains active for a longer period or if it recurs.
Diabetes insipidus is characterized by a great increase in the amount of urine passed (often several gallons per day) and an increased thirst. Any histiocytosis patient with an increase in drinking habits or passing large amounts of urine should be tested for DI.
Diabetes insipidus (DI, or AVP-D) is diagnosed with a water deprivation test, which measures changes in body weight, blood values, urine output, and urine composition when fluids are withheld over a several-hour period. It is very important that this test be supervised by a knowledgeable physician in a medical setting. An MRI scan is sometimes performed to see if there is change in the brain and pituitary area, but this test alone cannot diagnose DI.
Diabetes insipidus is usually a permanent, lifelong condition and cannot be cured. However, the symptoms of constant thirst and urination can be well controlled with treatment with DDAVP, a synthetic kind of vasopressin, and which can restore quality of life can be restored.
The most common symptoms associated with diabetes insipidus (DI) are extreme thirst and excessive urination. Some patients may drink as much as a full glass of fluids every 10 to 20 minutes. As DI may start in the toddler age group, the excessive thirst and asking for fluids may be misinterpreted as “bad behavior” or habit and parents may be mistakenly told to withhold fluids to break the habit. It is important that these children are allowed open access to fluids until treatment is started. If unable to find fluids easily, some children have been known to drink directly from faucets, baths, pet dishes, swimming pools, and other unusual sources around the home.
The extreme urination may continue throughout the day and the night, sometimes as often as every 15-20 minutes, and often includes bed-wetting. The urine is usually pale, without color.
Symptoms of diabetes insipidus are very similar to those of diabetes mellitus, except that the urine does not contain high sugar levels. Diabetes insipidus can interfere with appetite and eating. In children, it can interfere with growth and weight gain. Signs of dehydration often appear, since the body is unable to keep enough of the water it takes in.
Symptoms of dehydration include:
- Dry skin
- Dry mucous membranes (sticky mouth) /reduced tears
- Sunken appearance to eyes
- Sunken fontanelles (soft spot in the skull) in infants
- Weight loss
- Low body temperature
- Muscle pains
- Rapid heart rate
- Low blood pressure/shock
Adults with untreated DI may be able to drink enough water to make up for the extreme loss of urine. However, there is a serious risk of dehydration and imbalances in the blood, such as salt and potassium.
Most patients with diabetes insipidus have an abnormal appearance of the pituitary region on MRI scans of the head, although MRI alone does not diagnose DI. Children with DI are more prone to develop other hormone deficiencies later, mostly involving slower growth.
Patients who develop diabetes insipidus that is undiagnosed and untreated, report a dramatic decline in quality of life. Because of the extreme urination and thirst, activities of daily living can be greatly affected: work and school schedules are interrupted, and social events may be compromised. Sleeping through the night is often not possible, and travel is difficult. Because this disorder is so rare and often undiagnosed, it may be mistaken for diabetes mellitus. Other patients have been told that they have a “compulsive drinking disorder” and must withhold fluids; however, this can then become dangerous and even life-threatening. Once diagnosed and treated with synthetic vasopressin called DDAVP, symptoms quickly improve, and quality of life is restored.
Diagnosis and Treatment
The diagnosis of diabetes insipidus is based on a series of tests, including a urine osmolality and water deprivation test.
With diabetes insipidus, the urine is less concentrated with low salt and waste levels. The concentration of the urine can be tested by measuring osmolality, which is how many particles are in about a quart of water.
A water deprivation test is a complicated procedure that requires specially trained medical professionals. It should be done in a controlled setting where the patient can be monitored closely throughout the entire test. The water deprivation test measures changes in body weight, urine output, and the make-up of the urine, and levels of salts in the blood when fluids are withheld and as dehydration occurs. Measuring blood levels of the hormone ADH is also usually performed. Samples are taken every hour over a several-hour period.
An x-ray test called an MRI scan may be done to look for abnormalities in the pituitary gland, although alone, this is not diagnostic of diabetes insipidus. However, at diagnosis, it is estimated that 71% of patients show an abnormally thickened pituitary stalk on MRI.
Diabetes insipidus can be corrected by giving a synthetic vasopressin called DDAVP, which works on the kidneys to help decrease the amount of urine made. A normal balance between water intake and urine output is usually quickly restored. Most patients receive DDAVP as a pill or spray into the nose. However, if this is not possible due to the age or condition of the patient, DDAVP can be given by injection. It may be given in the hospital, clinic, or home. The dosage and method of receiving this hormone will depend on each individual case and should be discussed with your physician.
Fortunately, this treatment can be taken on trips, kept in the nurse’s office at school, and for other occasions when out of the home. Life-long treatment of diabetes insipidus is usually necessary.
Videos & Resources
Recently, an international study was conducted a collective of researchers and organizations. The DImond Survey sought to assess the characteristics of patients with central diabetes insipidus (DI) from diagnosis to management of the condition. The DImond Survey saw 1034 participants; the results of the study were presented at two international endocrinlology conferences this year and has been submitted for publication. We hope to share the results with you soon.
"Diabetes insipidus is a condition characterized by large volumes of unconcentrated urine, resulting in severe dehydration unless there is a compensating intake of fluids. The central form of diabetes insipidus is due to a deficiency in the hormone arginine vasopressin (AVP) in the posterior pituitary gland." Read about the organizations and researchers sponsoring this important initiative. Learn more about the results of the survey, here!
'Got DI?' Facebook Group, moderatered and managed by Pat Gilroy. This group is a supportive community for patients and families impacted by Diabetes Insipidus. While not all of these individuals have been impacted by histiocytosis, their journey will Diabetes Insipidus is similar and it is an excellent resource for connection and community. The Histiocytosis Association also extends gratitude to Pat Gilroy for all those you have impacted and for providing a wide range of resources to share.
Pituitary World News is a non-profit organization that seeks to increase awareness and reduce the number of undiagnosed and misdiagnosed people with a debilitating pituitary disease. PWN’s sole reason for being is to help diagnose people properly and early by increasing awareness of pituitary disorders and providing a platform for communications, collaborations, creativity, and innovation. Explore their Diabetes Insipidus resources, including a podcast and live talks. Many thanks to JD Faccinetti and Dr. Lewis Blevins for your partnership and for the amazing work you do.
Management of AVP-D Patient Card- A resource you can print out and put in a wallet or purse to have in case you need emergency care. This card gives possible points of care, which your doctor may need to adjust as necessary and is not a concrete standard of care.
Diabetes Inspidus Educational Video Series: The below series focuses on diabetes insipidus (which is now being called Arginine Vasopressin Deficiency). The video series is hosted by Professor John Wass, head of endocrinology at the University of Oxford, and Deborah Cooper, diabetes insipidus patient and were developed with The Pituitary Foundation.
The Pituitary Foundation offers a wide range of resources, including information on DI for patients and physicians. You can review their DI resources, here, or review the list below:
- Information on symptoms and diagnosis
- Living with DI For Teens Booklet
- Emergency Medical Care Card for DI Patients
- DI Toilet Access Card
- DI Awareness Card
- DI Care Guide for Schools
- Desmopressin Refusal Card (This letter has been produced for patients in an emergency situation, when refused desmopressin)
What Do I Do Now?
A new diagnosis of a histiocytic disorder can bring feelings of being overwhelmed, bewildered, scared, angry, sad, disappointed, helpless, and sometimes even feelings of guilt. It is a time filled with unknowns, change, and new people and situations. Most parents feel ill-equipped to understand what is happening to their child and how to navigate through the illness to recovery. There are, however, strategies and resources that can help you, your child, and other family members get through the uncertain times that lie ahead. One step at a time, you can gather information, create a support system, learn how to cope with stress, and become a strong advocate for your Histio Warrior as part of the medical team. The following tips and suggestions are provided to help guide you through this journey toward your Histio Warrior's good health.
Articles and Links
- Overview of Histiocytosis (Including Diabetes Insipidus)
- The Importance of Clinical Trials in the Fight Against Histiocytosis
- Diabetes Insipidus (National Institutes of Health)
- Risk Factors for Diabetes Insipidus in Langerhans Cell Histiocytosis
- Central Diabetes Insipidus: Is it Langerhans Cell Histiocytosis of the Pituitary Stalk?
- Central Diabetes Insipidus in Children and Young Adults
- Management of Langerhans Cell Hisitocytosis (LCH)-Induced Central Diabetes Insipidus and Its Associated Endocrinological/Neurological Sequelae
Printable Fact Sheets
Learn more about the different types of histiocytic disorders from these helpful fact sheets. Printing these for family and friends is a quick and easy way to teach them about the disease. More extensive information can be found in the Disease Information section of our website.
Choose from the following Fact Sheets: