Diabetes insipidus (DI) 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 is not known, because there has been no organized method to count the number of patients.
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 LCH. It is known to also occur in other histiocytic disorders, such as Rosai Dorfman and JXG.
It is believed that approximately between 5% and 50% of LCH 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 LCH remains active for a longer period or if it recurs.
Diabetes insipidus is recognized by a great increase in the amount of urine passed (often several gallons per day) and an increased thirst. Any patient with known LCH with an increase in drinking habits or passing large amounts of urine should be tested for DI.
Diabetes insipidus 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 x-ray test called 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 normal, symptom-free 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 a normal 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.
Two different types of hormones are involved: diabetes insipidus due to impaired production by the pituitary gland of a hormone called antidiuretic hormone and may occur as a consequence of histiocytosis. Diabetes mellitus, on the other hand, results from too much sugar in the blood, due to impaired insulin production by the pancreas. Although both disorders have similar symptoms of increased thirst and urination, in every other way including the cause and treatment, they are completely unrelated diseases.
DI occurs in as many as 25% of all patients and as many as 50% of patients with multisystem LCH.
The water-deprivation test is a complicated procedure that requires highly trained medical professionals to perform specialized measurements. The body’s water balance must be carefully monitored during the procedure to prevent rapid and dangerous dehydration.
This test includes timed measurements (some done every hour and others done every other hour) of blood pressure, pulse, weight, urine, and blood. Fluid is withheld during testing. The test may take up to 8 hours to complete, but it may be stopped sooner, depending on lab results. Further information and instructions will be provided by your physician.
Once DI has been diagnosed, the chance of reversal is uncommon. However, it has been reported in some cases where treatment was started within a few days of symptom onset.
DI can be the first presenting symptom, although one-half of these patients develop LCH lesions within 1 year after the onset of diabetes insipidus.
Yes. It is believed that this occurs in less than 10% of patients. The diagnosis is made from biopsy of the tumor in the pituitary stalk.
There is evidence that a rapid start of chemotherapy after onset of multisystem LCH may prevent DI.
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.
Histiocytosis can be considered a systemic illness; especially in cases where the disease is found in more than one system within the body. Some patients and caregivers may prefer to consult several specialists, depending on the different locations of symptoms. In this case, it is helpful to have one physician coordinate your care. An oncologist is usually the most appropriate choice.
Make sure that your doctor is someone you can trust and with whom you can communicate. Important qualities to look for in a doctor are:
- feeling as though you are heard,
- being given the opportunity to ask questions, and
- feeling respected.
If you are unsure about your physician, it is reasonable to schedule another appointment to discuss your concerns. While it is ideal to find a physician experienced and knowledgeable about histiocytic disorders, it is not always possible to find one who is nearby. If this is the case, ask the physician if he/she is open to a consultation with a knowledgeable physician and is willing to learn more about the disease. The Histiocytosis Association maintains a listing of doctors in a Physician Directory who have are knowledgeable about histiocytosis. You may also call us at +1 856-589-6606 for help finding other physicians in your area or for more information.
Call your insurance company to find out whether your plan will cover visits to the physician you are considering. Oftentimes a Team Social Worker and/or the hospital financial counselor can help smooth out insurance problems. Ask for help from a trusted friend if you feel overwhelmed in dealing with insurance issues.
Talking with your child: If your child is old enough to understand, sharing information can help him/her build trust in both you and his/her/your medical caregivers. It can also help your child cooperate with treatment and become a part of his/her/your medical team.
- Use words and ideas that are appropriate for your child’s age.
- Share information at a level that is in keeping with his/her ability to understand.
- Use your child’s questions as a guide to what he/she wants to know.
- Encourage your child to talk about his/her fears and concerns.
- Remind your child how much you love him/her.
If you are uncertain about how to talk to your child, your healthcare team can be of assistance.
Talking with family and friends: In the days and weeks following diagnosis, extended family and friends will need to be notified and periodically updated. However, explaining your situation multiple times can be exhausting and time-consuming. The Association offers a private Facebook group to help connect you with others. Some patients and families find that journaling is therapeutic and can provide an easy way to track their history and progress.
Talking with your child’s siblings: When your child is diagnosed with a histiocytic disorder, everyone in the family is affected, including brothers and sisters. They may feel anxious, lonely, resentful about the attention their sibling is getting, guilty about being healthy, or even responsible for the illness.
- Give information that is appropriate for your child’s age.
- Explain that no one did anything to cause the illness, and reassure them that it is not contagious.
- Give them a chance to talk about how the illness is affecting them or you. Be willing to answer questions.
- Remember that it will be easy for them to feel overlooked and unimportant, so it will be important to show that you love them and are proud of them.
Talking with your child’s school: Contact your school principal/counselor regarding your child’s diagnosis or if your diagnosis may affect your child. You may want to take brochures and other basic information about your histiocytic disorder. If your child is the patient, provide a written description of the health needs, such as what medications may need to be given at school, dosages, and times, signed by your physician. (Some schools will provide the form to be filled out and signed by your child’s physician.) Ask for a plan to take care of your child’s needs at school. You may need to provide written permission for the school to communicate with your physician, in case of an emergency.
Appointments: A calendar is a useful tool for remembering appointments and planning for changes to your established schedule. Calendars that show a week at a time also provide room on each day to record additional brief notes and reminders.
Medical Information: While some basic medical notes can be kept in a calendar, some patients and parents may choose to enter medical information in a laptop or keep a separate notebook. Be sure to date all entries. This information will be especially helpful when a new or different caregiver is involved. Examples that you may want to keep track of include:
- Results of various tests.
- A listing of allergies.
- A listing of medications and dosages.
- Names and phone numbers of your medical care team.
- Health information, such as your hospital number, social security number, and insurance information.
- Records of what was discussed during a medical visit/phone conversation and by whom.
- Notation of changing symptoms.
Adults may find it helpful to collect and organize medical records, starting as soon as possible after diagnosis. Although the original reports must remain in the physician or hospital file, you are legally entitled to copies of your records. You must submit a signed request for each physician’s office and the hospital. By keeping all records in one place, you can easily share these with other health care providers that you may see in the future. Follow this link to read more about obtaining your medical records.
If you have health insurance, it’s important that you know what your plan covers. Read your policy carefully to understand the health and medical services covered. Find out the portion of medical expenses you'll be responsible for paying. When you have questions or there are things you don’t understand, reach out to other experts available to you, such as the human resources personnel at your place of employment or financial counselors at your medical treatment center. If filing and tracking claims feels overwhelming, you may want to ask a trusted friend or relative to assist in managing your insurance issues.
When you call the insurance company, ask to work with one case manager. This may help simplify the process by having one person that knows your needs and can manage your claims. If possible, communicate with the same person on an ongoing basis. Remember to keep a journal of all encounters.
If you don’t have health insurance, if coverage is not adequate, or if you are not able to get insurance because of your pre-existing condition, you may qualify for your state’s high-risk insurance pool. You can obtain more information about whether your state participates at the National Association of State Comprehensive Health Insurance Plans website. If your state does not participate, you may qualify for the federal high-risk insurance pool. For more information, contact the U.S. Department of Health and Human Services.
Online: You can subscribe for our emails and you will receive important announcements regarding the latest information on the histiocytic disorders. The Association also maintains a Facebook page for families and patients with this disease.
Local support: The hospital where you or your child is being treated may have a support group for patients or parents of children with histiocytic disorders, rare diseases in general, or even cancer. Establishing face-to-face relationships with others going through similar experiences can be helpful.
The Association sponsors patient and family Regional meetings, which are held in various locations around the U.S. and hosted by Association staff and volunteers. They are a good opportunity to meet other families and patients, learn from expert physicians, receive and give emotional support, and share practical coping skills while also providing a time to relax, knowing you are with people who understand.
Fundraising events for histiocytic disorders are another way to make connections with families in your region. A listing of dates and fundraising events is provided on the Upcoming Events page.
Virtual opportunities to connect are also available.
Self-education about histiocytic disorders is an important part of advocating for your and your child. It will help you to make informed decisions about care and play a more active role in recovery.
The Association website provides education on a number of topics, including disease information, family resources, and past and ongoing research projects. The Histio Resource Directory provides an extensive listing of global, national, and state-by-state resources for patients and families. Some of the resources listed are informational, while others are service-based. A listing of past and current research projects funded by the Association can be found on the Grant Awards page, providing a glimpse into the past trends and current progress of research into the histiocytic disorders. The Disease Information section of the website features detailed, reliable information on all of the histiocytic disorders. This can be printed out and shared with medical caregivers, family, and friends if needed.
The Internet is a good source of information about histiocytosis and the treatment options, but the amount of information can be overwhelming, and the information is not always reliable. Some of it, in fact, is inaccurate. Reliable information is more likely to be found in more current documents that are free of grammatical and spelling errors, appear to be objective, are free of advertisements, and clearly state their sources.
It is essential to take an active role in your or your child’s health care. However, many patients and caregivers have little experience being advocates when they first receive a rare disease diganosis. The following is a list of essential tips for becoming a successful advocate:
- Learn about the diagnosed type of histiocytosis and become acquainted with the basic medical terms. Knowledge is empowerment.
- Know the warning signs that mean you may need emergency help.
- Know who to call in case of an emergency, and keep phone numbers handy.
- Keep a list of healthcare members involved in your medical care, along with contact information.
- If possible, take a companion (family member or friend) along on important medical appointments. The companion can help with remembering details of what was said and may assist by taking notes.
- Write down your questions before entering appointments or meetings and write down further questions as you think of them during the meeting. Don’t be afraid to ask these questions. This will be an important step in beginning to understand more about the disease. Medical information is often confusing and the language used by medical professionals is not easily understood, especially during stress. Whenever someone uses a word that you don’t understand, stop the conversation for a minute and ask the person to explain.
- Keep a healthcare notebook with a listing of allergies, medications, symptoms, and communications with healthcare providers.
- Find out about resources that the hospital provides, such as a social worker or patient representative. They can often assist with transportation costs, temporary housing if needed, parking fees, insurance issues, counseling, and other services.
- Be persistent in getting the care you feel that you or your child needs. Don’t hesitate to ask for what you need, and if you do not feel responded to, ask again or ask someone who will respond.
Trust your intuition. It can be a powerful decision-making tool. You know yourself or your child better than anyone else.
Being sick or caring for a sick child/loved one can be stressful and may take a toll on your physical and emotional health. Recognizing your own needs for support, help, health, and comfort can be difficult when you’re focused on the needs of others, but it’s important to remember that caring for yourself is essential. When your needs are taken care of, your loved ones will also benefit. Give yourself time for regular physical activity and rest. Pay attention to signs of stress, and consult your physician if you need further help.
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:
Histiocytic Disorders Overall FAQ
Histiocytic disorders are a diverse group of diseases caused by over-production of white blood cells known as histiocytes, which can lead to organ damage and tumor formation. They include a wide variety of conditions that can affect both children and adults.
The disorders are classified into three groups based on the types of histiocyte cells involved.
- The first group is called a dendritic cell disorder, and the most common disease in this group is Langerhans cell histiocytosis. Also included in this group are more rare diseases, juvenile xanthogranuloma (JXG) and Erdheim Chester.
- The second group is called a macrophage cell disorder, and includes primarily hemophagocytic lymphohistiocytosis (HLH) and Rosai-Dorfman.
- The third group is called malignant histiocytosis and includes certain kinds of leukemia and tumors.
All of the diseases are caused by the over-production of white blood cells called histiocytes. Their different classifications depend on the type of histiocyte involved.
The Histiocytosis Association’s online community provides a number of informational documents and articles, as well as links to medical articles about the histiocytic disorders. While the Internet does provide a significant volume of information about histiocytic disorders, some of this information is not accurate. It is important to look for documents that are current, are free of grammatical and spelling errors, appear to be objective, are free of advertisements, and clearly state their sources.
Histiocytosis is a rare disease that is caused by the over-production of a type of white cell that can lead to organ damage and the formation of tumors. The Histiocytosis Association’s Disease Fact Sheets are also a great way to help explain these complicated diseases to family and friends.
According to the Rare Disease Act of 2002, an orphan disease, also known as a rare disease, affects less than 200,000 persons in the U.S., or less than 1 in 1500 people. The criteria may vary in other countries. For example in Europe, an orphan disease is defined to occur in less than 1 in 2000.
According to the National Institutes of Health there are approximately 6800 such diseases. Combined, they affect nearly 30 million Americans.
- The National Organization for Rare Disorders (NORD) - Provides a patient information center, networking program, patient assistance programs, news about clinical trials, and a rare disease database.
- The National Institutes of Health (NIH) Office of Rare Diseases Research (ORDR) - Provides information on various topics related to rare diseases and links to numerous resources.
- EURORDIS – The Voice of Rare Disease Patients in Europe - An alliance of patient organizations representing 45 countries.
- Orphanet – Database/information about rare diseases with translation available in numerous languages.