The digestive system is made up of the gastrointestinal (GI) tractalso called the digestive tractand the liver, pancreas, and gallbladder. The GI tract is a series of hollow organs joined in a long, twisting tube from the mouth to the anus. The hollow organs that make up the GI tract are the mouth, esophagus, stomach, small intestine, large intestinewhich includes the colon and rectumand anus. Food enters the mouth and passes to the anus through the hollow organs of the digestive system. The liver, pancreas, and gallbladder are the solid organs of the digestive system. The digestive system helps the body digest food.


Alagille syndrome is caused by a gene mutation, or defect. Genes provide instructions for making proteins in the body. A gene mutation is a permanent change in the DNA sequence that makes up a gene. DNA, or deoxyribonucleic acid, is the material inside cells that carries genetic information and passes genes from parent to child. Approximately 30 to 50 percent of people with Alagille syndrome have an inherited gene mutation, meaning it has been passed on by a parent. In the remaining cases, the gene mutation develops spontaneously.1 In spontaneous cases, neither parent carries a copy of the mutated gene.

Most cases of Alagille syndrome are caused by a mutation in the JAGGED1 (JAG1) gene. In less than 1 percent of cases, a mutation in the NOTCH2 gene is the cause.2

Genetic Disorders   Each cell contains thousands of genes that provide the instructions for making proteins for growth and repair of the body. If a gene has a mutation, the protein made by that gene may not function properly, which sometimes creates a genetic disorder. Not all gene mutations cause a disorder.   People have two copies of most genes; one copy is inherited from each parent. A genetic disorder occurs when one or both parents pass a mutated gene to a child at conception. A genetic disorder can also occur through a spontaneous gene mutation, meaning neither parent carries a copy of the mutated gene. Once a spontaneous gene mutation has occurred in a person, it can be passed to the person's children.   Read more about genes and genetic conditions at the U.S. National Library of Medicine's (NLM's) Genetics Home Reference at www.ghr.nlm.nih.gov.


Alagille syndrome occurs in about one of every 30,000 live births.3 The disorder affects both sexes equally and shows no geographical, racial, or ethnic preferences.

JAG1 and NOTCH2 gene mutations are inherited in an autosomal dominant way, which means a child can get Alagille syndrome by inheriting either of the gene mutations from only one parent. Each child of a parent with an autosomal dominant mutation has a 50 percent chance of inheriting the mutated gene.

The following chart shows the chance of inheriting an autosomal dominant gene mutation:

The gene mutations that cause Alagille syndrome may cause mild or subtle symptoms. Some people may not know they are affected, while others with the gene mutation may develop more serious characteristics of Alagille syndrome. A person with a gene mutation, whether showing serious symptoms or not, has Alagille syndrome and can pass the gene mutation to a child.

Read more about how genetic conditions are inherited at the NLM's Genetics Home Reference website at www.ghr.nlm.nih.gov.


The signs and symptoms of Alagille syndrome and their severity vary, even among people in the same family sharing the same gene mutation.

Liver

In some people, problems in the liver may be the first signs and symptoms of the disorder. These signs and symptoms can occur in children and adults with Alagille syndrome, and in infants as early as the first 3 months of life.

Jaundice. Jaundicewhen the skin and whites of the eyes turn yellowis a result of the liver not removing bilirubin from the blood. Bilirubin is a reddish-yellow substance formed when hemoglobin breaks down. Hemoglobin is an iron-rich protein that gives blood its red color. Bilirubin is absorbed by the liver, processed, and released into bile. Blockage of the bile ducts forces bilirubin and other elements of bile to build up in the blood.

Jaundice may be difficult for parents and even health care providers to detect. Many healthy newborns have mild jaundice during the first 1 to 2 weeks of life due to an immature liver. This normal type of jaundice disappears by the second or third week of life, whereas the jaundice of Alagille syndrome deepens. Newborns with jaundice after 2 weeks of life should be seen by a health care provider to check for a possible liver problem.

Dark urine and gray or white stools. High levels of bilirubin in the blood that pass into the urine can make the urine darker, while stool lightens from a lack of bilirubin reaching the intestines. Gray or white bowel movements after 2 weeks of age are a reliable sign of a liver problem and should prompt a visit to a health care provider.

Pruritus. The buildup of bilirubin in the blood may cause itching, also called pruritus. Pruritus usually starts after 3 months of age and can be severe.

Xanthomas. Xanthomas are fatty deposits that appear as yellow bumps on the skin. They are caused by abnormally high cholesterol levels in the blood, common in people with liver disease. Xanthomas may appear anywhere on the body. However, xanthomas are usually found on the elbows, joints, tendons, knees, hands, feet, or buttocks.

Other Signs and Symptoms of Alagille Syndrome

Certain signs of Alagille syndrome are unique to the disorder, including those that affect the vertebrae and facial features.

Face. Many children with Alagille syndrome have deep-set eyes, a straight nose, a small and pointed chin, large ears, and a prominent, wide forehead. These features are not usually recognized until after infancy. By adulthood, the chin is more prominent.

Eyes. Posterior embryotoxon is a condition in which an opaque ring is present in the cornea, the transparent covering of the eyeball. The abnormality is common in people with Alagille syndrome, though it usually does not affect vision.

Skeleton. The most common skeletal defect in a person with Alagille syndrome is when the shape of the vertebraebones of the spinegives the appearance of flying butterflies. This defect, known as "butterfly" vertebrae, rarely causes medical problems or requires treatment.

Heart and blood vessels. People with Alagille syndrome may have the following signs and symptoms having to do with the heart and blood vessels:

- heart murmuran extra or unusual sound heard during a heartbeat. A heart murmur is the most common sign of Alagille syndrome other than the general symptoms of liver disease.1 Most people with Alagille syndrome have a narrowing of the blood vessels that carry blood from the heart to the lungs.1 This narrowing causes a murmur that can be heard with a stethoscope. Heart murmurs usually do not cause problems.  - heart walls and valve problems. A small number of people with Alagille syndrome have serious problems with the walls or valves of the heart. These conditions may need treatment with medications or corrective surgery.  - blood vessel problems. People with Alagille syndrome may have abnormalities of the blood vessels in the head and neck. This serious complication can lead to internal bleeding or stroke. Alagille syndrome can also cause narrowing or bulging of other blood vessels in the body.

Kidney disease. A wide range of kidney diseases can occur in Alagille syndrome. The kidneys are two bean-shaped organs, each about the size of a fist, that filter wastes and extra fluid from the blood. Some people have small kidneys or have cystsfluid-filled sacsin the kidneys. Kidney function can also decrease.


The complications of Alagille syndrome include liver failure, portal hypertension, and growth problems. People with Alagille syndrome usually have a combination of complications, and may not have every complication listed below.

Liver failure. Over time, the decreased number of bile ducts may lead to chronic liver failure, also called end-stage liver disease. This condition progresses over months, years, or even decades. The liver can no longer perform important functions or effectively replace damaged cells. A person may need a liver transplant. A liver transplant is surgery to remove a diseased or an injured liver and replace it with a healthy whole liver or a segment of a liver from another person, called a donor.

Portal hypertension. The spleen is the organ that cleans blood and makes white blood cells. White blood cells attack bacteria and other foreign cells. Blood flow from the spleen drains directly into the liver. When a person with Alagille syndrome has advanced liver disease, the blood flow backs up into the spleen and other blood vessels. This condition is called portal hypertension. The spleen may become larger in the later stages of liver disease. A person with an enlarged spleen should avoid contact sports to protect the organ from injury. Advanced portal hypertension can lead to serious bleeding problems.

Growth problems. Alagille syndrome can lead to poor growth in infants and children, as well as delayed puberty in older children. Liver disease can cause malabsorption, which can result in growth problems. Malabsorption is the inability of the small intestine to absorb nutrients from foods, which results in protein, calorie, and vitamin deficiencies. Serious heart problems, if present in Alagille syndrome, can also affect growth.

Malabsorption. People with Alagille syndrome may have diarrhealoose, watery stoolsdue to malabsorption. The condition occurs because bile is necessary for the digestion of food. Malabsorption can lead to bone fractures, eye problems, blood-clotting problems, and learning delays.

Long-term Outlook

The long-term outlook for people with Alagille syndrome depends on several factors, including the severity of liver damage and heart problems. Predicting who will experience improved bile flow and who will progress to chronic liver failure is difficult. Ten to 30 percent of people with Alagille syndrome will eventually need a liver transplant.3

Many adults with Alagille syndrome whose symptoms improve with treatment lead normal, productive lives. Deaths in people with Alagille syndrome are most often caused by chronic liver failure, heart problems, and blood vessel problems.


A health care provider diagnoses Alagille syndrome by performing a thorough physical exam and ordering one or more of the following tests and exams:

- blood test  - urinalysis  - x ray  - abdominal ultrasound  - cardiology exam  - slit-lamp exam  - liver biopsy  - genetic testing

Alagille syndrome can be difficult to diagnose because the signs and symptoms vary and the syndrome is so rare.

For a diagnosis of Alagille syndrome, three of the following symptoms typically should be present:

- liver symptoms, such as jaundice, pruritus, malabsorption, and xanthomas  - heart abnormalities or murmurs  - skeletal abnormalities  - posterior embryotoxon  - facial features typical of Alagille syndrome  - kidney disease  - blood vessel problems

A health care provider may perform a liver biopsy to diagnose Alagille syndrome; however, it is not necessary to make a diagnosis. A diagnosis can be made in a person who does not meet the clinical criteria of Alagille syndrome yet does have a gene mutation of JAG1. The health care provider may have a blood sample tested to look for the JAG1 gene mutation. The gene mutation can be identified in 94 percent of people with a diagnosis of Alagille syndrome.2

Blood test. A blood test involves drawing blood at a health care provider's office or a commercial facility and sending the sample to a lab for analysis. The blood test can show nutritional status and the presence of liver disease and kidney function.

Urinalysis. Urinalysis is the testing of a urine sample. The urine sample is collected in a special container in a health care provider's office or a commercial facility and can be tested in the same location or sent to a lab for analysis. Urinalysis can show many problems of the urinary tract and other body systems. The sample may be observed for color, cloudiness, or concentration; signs of drug use; chemical composition, including glucose; the presence of protein, blood cells, or bacteria; or other signs of disease.

X ray. An x ray is a picture created by using radiation and recorded on film or on a computer. The amount of radiation used is small. An x-ray technician performs the x ray at a hospital or an outpatient center, and a radiologista doctor who specializes in medical imaginginterprets the images. Anesthesia is not needed. The patient will lie on a table or stand during the x ray. The technician positions the x-ray machine over the spine area to look for "butterfly" vertebrae. The patient will hold his or her breath as the picture is taken so that the picture will not be blurry. The patient may be asked to change position for additional pictures.

Abdominal ultrasound. Ultrasound uses a device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure. The transducer can be moved to different angles to make it possible to examine different organs. In abdominal ultrasound, the health care provider applies a gel to the patient's abdomen and moves a handheld transducer over the skin. The gel allows the transducer to glide easily, and it improves the transmission of the signals. A specially trained technician performs the procedure in a health care provider's office, an outpatient center, or a hospital, and a radiologist interprets the images; anesthesia is not needed. The images can show an enlarged liver or rule out other conditions.

Cardiology exam. A cardiologista doctor who treats people who have heart problemsperforms a cardiology exam in a health care provider's office, an outpatient center, or a hospital. During a full exam, a cardiologist may inspect the patient's physical appearance, measure pulse rate and blood pressure, observe the jugular vein, check for rapid or skipped heartbeats, listen for variations in heart sounds, and listen to the lungs.

Slit-lamp exam. An ophthalmologista doctor who diagnoses and treats all eye diseases and eye disordersperforms a slit-lamp exam to diagnose posterior embryotoxon. The ophthalmologist examines the eye with a slit lamp, a microscope combined with a high-intensity light that shines a thin beam on the eye. While sitting in a chair, the patient will rest his or her head on the slit lamp. A yellow dye may be used to examine the cornea and tear layer. The dye is applied as a drop, or the specialist may touch a strip of paper stained with the dye to the white of the patient's eye. The specialist will also use drops in the patient's eye to dilate the pupil.

Liver biopsy. A liver biopsy is a procedure that involves taking a piece of liver tissue for examination with a microscope for signs of damage or disease. The health care provider may ask the patient to stop taking certain medications temporarily before the liver biopsy. The patient may be asked to fast for 8 hours before the procedure.

During the procedure, the patient lies on a table, right hand resting above the head. A local anesthetic is applied to the area where the biopsy needle will be inserted. If needed, sedatives and pain medication are also given. The health care provider uses a needle to take a small piece of liver tissue. The health care provider may use ultrasound, computerized tomography scans, or other imaging techniques to guide the needle. After the biopsy, the patient should lie on the right side for up to 2 hours and is monitored an additional 2 to 4 hours before being sent home.

Genetic testing. The health care provider may refer a person suspected of having Alagille syndrome to a geneticista doctor who specializes in genetic disorders. For a genetic test, the geneticist takes a blood or saliva sample and analyzes the DNA for the JAG1 gene mutation. The geneticist tests for the JAG1 gene mutation first, since it is more common in Alagille syndrome than NOTCH2. Genetic testing is often done only by specialized labs. The results may not be available for several months because of the complexity of the testing.

The usefulness of genetic testing for Alagille syndrome is limited by two factors:

- Detection of a mutated gene cannot predict the onset of symptoms or how serious the disorder will be.  - Even if a mutated gene is found, no specific cure for the disorder exists.

When to Consider Genetic Counseling   People who are considering genetic testing may want to consult a genetics counselor. Genetic counseling can help family members understand how test results may affect them individually and as a family. Genetic counseling is provided by genetics professionalshealth care professionals with specialized degrees and experience in medical genetics and counseling. Genetics professionals include geneticists, genetics counselors, and genetics nurses.   Genetics professionals work as members of health care teams, providing information and support to individuals or families who have genetic disorders or a higher chance of having an inherited condition. Genetics professionals   - assess the likelihood of a genetic disorder by researching a family's history, evaluating medical records, and conducting a physical exam of the patient and other family members   - weigh the medical, social, and ethical decisions surrounding genetic testing   - provide support and information to help a person make a decision about testing   - interpret the results of genetic tests and medical data   - provide counseling or refer individuals and families to support services   - serve as patient advocates   - explain possible treatments or preventive measures   - discuss reproductive options    Genetic counseling may be useful when a family member is deciding whether to have genetic testing and again later when test results are available.


Treatment for Alagille syndrome includes medications and therapies that increase the flow of bile from the liver, promote growth and development in infants' and children's bodies, correct nutritional deficiencies, and reduce the person's discomfort. Ursodiol (Actigall, Urso) is a medication that increases bile flow. Other treatments address specific symptoms of the disorder.

Liver failure. People with Alagille syndrome who develop end-stage liver failure need a liver transplant with a whole liver from a deceased donor or a segment of a liver from a living donor. People with Alagille syndrome who also have heart problems may not be candidates for a transplant because they could be more likely to have complications during and after the procedure. A liver transplant surgical team performs the transplant in a hospital.

More information is provided in the NIDDK health topic, Liver Transplantation.

Pruritus. Itching may decrease when the flow of bile from the liver is increased. Medications such as cholestyramine (Prevalite), rifampin (Rifadin, Rimactane), naltrexone (Vivitrol), or antihistamines may be prescribed to relieve pruritus. People should hydrate their skin with moisturizers and keep their fingernails trimmed to prevent skin damage from scratching. People with Alagille syndrome should avoid baths and take short showers to prevent the skin from drying out.

If severe pruritus does not improve with medication, a procedure called partial external biliary diversion may provide relief from itching. The procedure involves surgery to connect one end of the small intestine to the gallbladder and the other end to an opening in the abdomencalled a stomathrough which bile leaves the body and is collected in a pouch. A surgeon performs partial external biliary diversion in a hospital. The patient will need general anesthesia.

Malabsorption and growth problems. Infants with Alagille syndrome are given a special formula that helps the small intestine absorb much-needed fat. Infants, children, and adults can benefit from a high-calorie diet, calcium, and vitamins A, D, E, and K. They may also need additional zinc. If someone with Alagille syndrome does not tolerate oral doses of vitamins, a health care provider may give the person injections for a period of time. A child may receive additional calories through a tiny tube that is passed through the nose into the stomach. If extra calories are needed for a long time, a health care provider may place a tube, called a gastrostomy tube, directly into the stomach through a small opening made in the abdomen. A child's growth may improve with increased nutrition and flow of bile from the liver.

Xanthomas. For someone who has Alagille syndrome, these fatty deposits typically worsen over the first few years of life and then improve over time. They may eventually disappear in response to partial external biliary diversion or the medications used to increase bile flow.


Scientists have not yet found a way to prevent Alagille syndrome. However, complications of the disorder can be managed with the help of health care providers. Routine visits with a health care team are needed to prevent complications from becoming worse.


Researchers have not found that eating, diet, and nutrition play a role in causing or preventing Alagille syndrome. However, these factors are important for people with Alagille syndrome, particularly children, who are malnourished, growing poorly, or have delayed puberty. Caregivers and parents of children with Alagille syndrome should try to maximize their children's potential for growth through good eating, diet, and nutrition.

A nutritionist or a dietitiana person with training in nutrition and dietcan work with someone with Alagille syndrome and his or her health care team to build an appropriate healthy eating plan. A person with Alagille syndrome may need to take dietary supplements or vitamins in addition to eating a set number of calories, based on the type of complications the person has. Researchers consider good nutrition to be one of the most important aspects of managing the disorder.

If potential liver problems are present, a person with Alagille syndrome should not drink alcoholic beverages without talking with his or her health care provider first.

Additionally, eating, diet, and nutrition play a part in overall health and preventing further health problems.


- Alagille syndrome is a genetic condition that results in various symptoms in different parts of the body, including the liver.  - A person with Alagille syndrome has fewer than the normal number of small bile ducts inside the liver.  - In people with Alagille syndrome, the decreased number of bile ducts causes bile to build up in the liver, a condition also called cholestasis, leading to liver damage and liver disease.  - Alagille syndrome is caused by a gene mutation, or defect. Approximately 30 to 50 percent of people with Alagille syndrome have an inherited gene mutation, meaning it has been passed on by a parent.  - Alagille syndrome occurs in about one of every 30,000 live births. The disorder affects both sexes equally and shows no geographical, racial, or ethnic preferences.  - The gene mutations that cause Alagille syndrome may cause mild or subtle symptoms. Some people may not know they are affected.  - The signs and symptoms of Alagille syndrome and their severity vary, even among people in the same family sharing the same gene mutation.  - In some people, problems in the liver may be the first signs and symptoms of the disorder.  - The complications of Alagille syndrome include liver failure, portal hypertension, and growth problems.  - Ten to 30 percent of people with Alagille syndrome will eventually need a liver transplant.  - A health care provider diagnoses Alagille syndrome by performing a thorough physical exam and other tests.  - Genetic counseling can help family members understand how genetic test results may affect them individually and as a family.  - Treatment for Alagille syndrome includes medications and therapies that increase the flow of bile from the liver, promote growth and development in infants' and children's bodies, correct nutritional deficiencies, and reduce the person's discomfort.  - Scientists have not yet found a way to prevent Alagille syndrome.  - Caregivers and parents of children with Alagille syndrome should try to maximize their children's potential for growth through good eating, diet, and nutrition.


Too much glucose in the blood for a long time can cause diabetes problems. This high blood glucose, also called blood sugar, can damage many parts of the body, such as the heart, blood vessels, eyes, and kidneys. Heart and blood vessel disease can lead to heart attacks and strokes, the leading causes of death for people with diabetes. You can do a lot to prevent or slow down diabetes problems.

This booklet is about heart and blood vessel problems caused by diabetes. You will learn the things you can do each day and during each year to stay healthy and prevent diabetes problems.


You can do a lot to prevent heart disease and stroke.

- Keep your blood glucose under control. You can see if your blood glucose is under control by having an A1C test at least twice a year. The A1C test tells you your average blood glucose for the past 2 to 3 months. The target for most people with diabetes is below 7. In some people with heart disease or other special circumstances, their doctor may recommend slightly higher levels of A1C.  - Keep your blood pressure under control. Have it checked at every doctor visit. The target for most people with diabetes is below 140/80, unless their doctor sets a different target.  - Keep your cholesterol under control. Have it checked at least once a year. The targets for most people with diabetes are      - LDLbadcholesterol: below 100    - HDLgoodcholesterol: above 40 in men and above 50 in women    - triglyceridesanother type of fat in the blood: below 150    - Make sure the foods you eat are "heart-healthy." Include foods high in fiber, such as oat bran, oatmeal, whole-grain breads and cereals, fruits, and vegetables. Cut back on foods high in saturated fat or cholesterol, such as meats, butter, dairy products with fat, eggs, shortening, lard, and foods with palm oil or coconut oil. Limit foods with trans fat, such as snack foods and commercial baked goods.  - If you smoke, quit. Your doctor can tell you about ways to help you quit smoking.  - Ask your doctor whether you should take an aspirin every day. Studies have shown that taking a low dose of aspirin every day can help reduce your risk of heart disease and stroke.  - Take your medicines as directed.


You may have one or more of the following warning signs:

- chest pain or discomfort  - pain or discomfort in your arms, back, jaw, or neck  - indigestion or stomach pain  - shortness of breath  - sweating  - nausea  - light-headedness

Or, you may have no warning signs at all. Warning signs may come and go. If you have any of these warning signs, call 911 right away. Getting prompt treatment can reduce damage to the heart.


Narrowed blood vessels leave a smaller opening for blood to flow through. Having narrowed blood vessels is like turning on a garden hose and holding your thumb over the opening. The smaller opening makes the water shoot out with more pressure. In the same way, narrowed blood vessels lead to high blood pressure. Other factors, such as kidney problems and being overweight, also can lead to high blood pressure.

Many people with diabetes also have high blood pressure. If you have heart, eye, or kidney problems from diabetes, high blood pressure can make them worse.

You will see your blood pressure written with two numbers separated by a slash. For example, your reading might be 120/70, said as "120 over 70." For most people with diabetes, the target is to keep the first number below 140 and the second number below 80, unless their doctor sets a different target.

If you have high blood pressure, ask your doctor how to lower it. Your doctor may ask you to take blood pressure medicine every day. Some types of blood pressure medicine can also help keep your kidneys healthy.

You may also be able to control your blood pressure by

- eating more fruits and vegetables  - eating less salt and high-sodium foods  - losing weight if you need to  - being physically active  - not smoking  - limiting alcoholic drinks


A stroke happens when part of your brain is not getting enough blood and stops working. Depending on the part of the brain that is damaged, a stroke can cause

- sudden weakness or numbness of your face, arm, or leg on one side of your body  - sudden confusion, trouble talking, or trouble understanding  - sudden dizziness, loss of balance, or trouble walking  - sudden trouble seeing in one or both eyes or sudden double vision  - sudden severe headache

Sometimes, one or more of these warning signs may happen and then disappear. You might be having a "mini-stroke," also called a TIA or a transient ischemic attack. If you have any of these warning signs, call 911 right away. Getting care for a TIA may reduce or prevent a stroke. Getting prompt treatment for a stroke can reduce the damage to the brain and improve chances for recovery.


- Don't smoke.  - Keep blood glucose and blood pressure under control.  - Keep blood fats close to normal.  - Be physically active.  - Ask your doctor if you should take aspirin every day.

You also may need surgery to treat PAD.


Primary hyperparathyroidism is a disorder of the parathyroid glands, also called parathyroids. Primary means this disorder originates in the parathyroid glands. In primary hyperparathyroidism, one or more of the parathyroid glands are overactive. As a result, the gland releases too much parathyroid hormone (PTH). The disorder includes the problems that occur in the rest of the body as a result of too much PTHfor example, loss of calcium from bones.

In the United States, about 100,000 people develop primary hyperparathyroidism each year.1 The disorder is diagnosed most often in people between age 50 and 60, and women are affected about three times as often as men.2

Secondary, or reactive, hyperparathyroidism can occur if a problem such as kidney failure causes the parathyroid glands to be overactive.


The parathyroid glands are four pea-sized glands located on or near the thyroid gland in the neck. Occasionally, a person is born with one or more of the parathyroid glands in another location. For example, a gland may be embedded in the thyroid, in the thymusan immune system organ located in the chestor elsewhere around this area. In most such cases, however, the parathyroid glands function normally.

The parathyroid glands are part of the bodys endocrine system. Endocrine glands produce, store, and release hormones, which travel in the bloodstream to target cells elsewhere in the body and direct the cells activity.

Though their names are similar, the thyroid and parathyroid glands are entirely different glands, each producing distinct hormones with specific functions. The parathyroid glands produce PTH, a hormone that helps maintain the correct balance of calcium in the body. PTH regulates the level of calcium in the blood, release of calcium from bone, absorption of calcium in the small intestine, and excretion of calcium in the urine.

When the level of calcium in the blood falls too low, normal parathyroid glands release just enough PTH to restore the blood calcium level.


High PTH levels trigger the bones to release increased amounts of calcium into the blood, causing blood calcium levels to rise above normal. The loss of calcium from bones may weaken the bones. Also, the small intestine may absorb more calcium from food, adding to the excess calcium in the blood. In response to high blood calcium levels, the kidneys excrete more calcium in the urine, which can lead to kidney stones.

High blood calcium levels might contribute to other problems, such as heart disease, high blood pressure, and difficulty with concentration. However, more research is needed to better understand how primary hyperparathyroidism affects the cardiovascular systemthe heart and blood vesselsand the central nervous systemthe brain and spinal cord.


In about 80 percent of people with primary hyperparathyroidism, a benign, or noncancerous, tumor called an adenoma has formed in one of the parathyroid glands.2 The tumor causes the gland to become overactive. In most other cases, the excess hormone comes from two or more overactive parathyroid glands, a condition called multiple tumors or hyperplasia. Rarely, primary hyperparathyroidism is caused by cancer of a parathyroid gland.

In most cases, health care providers dont know why adenoma or multiple tumors occur in the parathyroid glands. Most people with primary hyperparathyroidism have no family history of the disorder, but some cases can be linked to an inherited problem. For example, familial multiple endocrine neoplasia type 1 is a rare, inherited syndrome that causes multiple tumors in the parathyroid glands as well as in the pancreas and the pituitary gland. Another rare genetic disorder, familial hypocalciuric hypercalcemia, causes a kind of hyperparathyroidism that is atypical, in part because it does not respond to standard parathyroid surgery.


Most people with primary hyperparathyroidism have no symptoms. When symptoms appear, they are often mild and nonspecific, such as

- muscle weakness  - fatigue and an increased need for sleep  - feelings of depression  - aches and pains in bones and joints

People with more severe disease may have

- loss of appetite  - nausea  - vomiting  - constipation  - confusion or impaired thinking and memory  - increased thirst and urination

These symptoms are mainly due to the high blood calcium levels that result from excessive PTH.


Health care providers diagnose primary hyperparathyroidism when a person has high blood calcium and PTH levels. High blood calcium is usually the first sign that leads health care providers to suspect parathyroid gland overactivity. Other diseases can cause high blood calcium levels, but only in primary hyperparathyroidism is the elevated calcium the result of too much PTH.

Routine blood tests that screen for a wide range of conditions, including high blood calcium levels, are helping health care providers diagnose primary hyperparathyroidism in people who have mild forms of the disorder and are symptom-free. For a blood test, blood is drawn at a health care providers office or commercial facility and sent to a lab for analysis.


Once the diagnosis of primary hyperparathyroidism is established, other tests may be done to assess complications:

- Bone mineral density test. Dual energy x-ray absorptiometry, sometimes called a DXA or DEXA scan, uses low-dose x rays to measure bone density. During the test, a person lies on a padded table while a technician moves the scanner over the persons body. DXA scans are performed in a health care providers office, outpatient center, or hospital by a specially trained technician and may be interpreted by a metabolic bone disease expert or radiologista doctor who specializes in medical imagingor other specialists; anesthesia is not needed. The test can help assess bone loss and risk of fractures.  - Ultrasound. Ultrasound uses a device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure. The procedure is performed in a health care providers office, outpatient center, or hospital by a specially trained technician, and the images are interpreted by a radiologist; anesthesia is not needed. The images can show the presence of kidney stones.  - Computerized tomography (CT) scan. CT scans use a combination of x rays and computer technology to create three-dimensional (3-D) images. A CT scan may include the injection of a special dye, called contrast medium. CT scans require the person to lie on a table that slides into a tunnel-shaped device where the x rays are taken. The procedure is performed in an outpatient center or hospital by an x-ray technician, and the images are interpreted by a radiologist; anesthesia is not needed. CT scans can show the presence of kidney stones.  - Urine collection. A 24-hour urine collection may be done to measure selected chemicals, such as calcium and creatinine, which is a waste product healthy kidneys remove. The person collects urine over a 24-hour period, and the urine is sent to a laboratory for analysis. The urine collection may provide information on kidney damage, the risk of kidney stone formation, and the risk of familial hypocalciuric hypercalcemia.  - 25-hydroxy-vitamin D blood test. This test is recommended because vitamin D deficiency is common in people with primary hyperparathyroidism.


Surgery

Surgery to remove the overactive parathyroid gland or glands is the only definitive treatment for the disorder, particularly if the patient has a very high blood calcium level or has had a fracture or a kidney stone. In patients without any symptoms, guidelines are used to identify who might benefit from parathyroid surgery.3

When performed by experienced endocrine surgeons, surgery cures primary hyperparathyroidism in more than 95 percent of operations.2

Surgeons often use imaging tests before surgery to locate the overactive gland to be removed. The most commonly used tests are sestamibi and ultrasound scans. In a sestamibi scan, the patient receives an injection of a small amount of radioactive dye that is absorbed by overactive parathyroid glands. The overactive glands can then be viewed using a special camera.

Surgeons use two main strategies to remove the overactive gland or glands:

- Minimally invasive parathyroidectomy. This type of surgery, which can be done on an outpatient basis, may be used when only one of the parathyroid glands is likely to be overactive. Guided by a tumor-imaging test, the surgeon makes a small incision in the neck to remove the gland. The small incision means that patients typically have less pain and a quicker recovery than with more invasive surgery. Local or general anesthesia may be used for this type of surgery.  - Standard neck exploration. This type of surgery involves a larger incision that allows the surgeon to access and examine all four parathyroid glands and remove the overactive ones. This type of surgery is more extensive and typically requires a hospital stay of 1 to 2 days. Surgeons use this approach if they plan to inspect more than one gland. General anesthesia is used for this type of surgery.

Almost all people with primary hyperparathyroidism who have symptoms can benefit from surgery. Experts believe that those without symptoms but who meet guidelines for surgery will also benefit from surgery. Surgery can lead to improved bone density and fewer fractures and can reduce the chance of forming kidney stones. Other potential benefits are being studied by researchers.

Surgery for primary hyperparathyroidism has a complication rate of 13 percent when performed by experienced endocrine surgeons.4 Rarely, patients undergoing surgery experience damage to the nerves controlling the vocal cords, which can affect speech. A small number of patients lose all their healthy parathyroid tissue and thus develop chronic low calcium levels, requiring lifelong treatment with calcium and some form of vitamin D. This complication is called hypoparathyroidism. The complication rate is slightly higher for operations on multiple tumors than for a single adenoma because more extensive surgery is needed.

People with primary hyperparathyroidism due to familial hypocalciuric hypercalcemia should not have surgery.

Monitoring

Some people who have mild primary hyperparathyroidism may not need immediate or even any surgery and can be safely monitored. People may wish to talk with their health care provider about long-term monitoring if they

- are symptom-free  - have only slightly elevated blood calcium levels  - have normal kidneys and bone density

Long-term monitoring should include periodic clinical evaluations, annual serum calcium measurements, annual serum creatinine measurements to check kidney function, and bone density measurements every 1 to 2 years.

Vitamin D deficiency should be corrected if present. Patients who are monitored need not restrict calcium in their diets.

If the patient and health care provider choose long-term monitoring, the patient should

- drink plenty of water  - exercise regularly  - avoid certain diuretics, such as thiazides

Either immobilizationthe inability to move due to illness or injuryor gastrointestinal illness with vomiting or diarrhea that leads to dehydration can cause blood calcium levels to rise further in someone with primary hyperparathyroidism. People with primary hyperparathyroidism should seek medical attention if they find themselves immobilized or dehydrated due to vomiting or diarrhea.

Medications

Calcimimetics are a new class of medications that decrease parathyroid gland secretion of PTH. The calcimimetic, cinacalcet (Sensipar), has been approved by the U.S. Food and Drug Administration for the treatment of secondary hyperparathyroidism caused by dialysisa blood-filtering treatment for kidney failureand primary hyperparathyroidism caused by parathyroid cancer. Cinacalcet has also been approved for the management of hypercalcemia associated with primary hyperparathyroidism.

A number of other medications are being studied to learn whether they may be helpful in treating primary hyperparathyroidism. These medications include bisphosphonates and selective estrogen receptor modulators.


Eating, diet, and nutrition have not been shown to play a role in causing or preventing primary hyperparathyroidism.

Vitamin D. Experts suggest correcting vitamin D deficiency in people with primary hyperparathyroidism to achieve a serum level of 25-hydroxy-vitamin D greater than 20 nanograms per deciliter (50 nanomoles per liter). Research is ongoing to determine optimal doses and regimens of vitamin D supplementation for people with primary hyperparathyroidism.

For the healthy public, the Institute of Medicine (IOM) guidelines for vitamin D intake are

- people ages 1 to 70 years may require 600 International Units (IUs)  - people age 71 and older may require as much as 800 IUs

The IOM also recommends that no more than 4,000 IUs of vitamin D be taken per day.

Calcium. People with primary hyperparathyroidism without symptoms who are being monitored do not need to restrict calcium in their diet. People with low calcium levels due to loss of all parathyroid tissue from surgery will need to take calcium supplements for the rest of their life.

To help ensure coordinated and safe care, people should discuss their use of complementary and alternative medicine practices, including their use of dietary supplements, with their health care provider. Tips for talking with health care providers are available through the National Center for Complementary and Integrative Health.


- Primary hyperparathyroidism is a disorder of the parathyroid glands, in which one or more of the parathyroid glands are overactive. As a result, the gland releases too much parathyroid hormone (PTH).  - High PTH levels trigger the bones to release increased calcium into the blood, causing blood calcium levels to rise above normal. T he loss of calcium from bones may weaken the bones. In response to high blood calcium levels, the kidneys excrete more calcium in the urine, which can lead to kidney stones.  - Most people with primary hyperparathyroidism have no symptoms. When symptoms appear, they are often mild and nonspecific, such as muscle weakness, fatigue, increased need for sleep, feelings of depression, or aches and pains in bones and joints.  - People with more severe primary hyperparathyroidism may have symptoms such as loss of appetite, nausea, vomiting, constipation, confusion or impaired thinking and memory, and increased thirst and urination.  - Health care providers diagnose primary hyperparathyroidism when a person has high blood calcium and PTH levels.  - Surgery to remove the overactive parathyroid gland or glands is the only definitive treatment for the disorder. When performed by experienced endocrine surgeons, surgery cures primary hyperparathyroidism in more than 95 percent of operations. Some people who have mild primary hyperparathyroidism may not need immediate or even any surgery and can be safely monitored. People with primary hyperparathyroidism due to familial hypocalciuric hypercalcemia should not have surgery.


Urinary incontinence is the loss of bladder control, resulting in the accidental leakage of urine from the body. For example, a man may feel a strong, sudden need, or urgency, to urinate just before losing a large amount of urine, called urgency incontinence.

UI can be slightly bothersome or totally debilitating. For some men, the chance of embarrassment keeps them from enjoying many activities, including exercising, and causes emotional distress. When people are inactive, they increase their chances of developing other health problems, such as obesity and diabetes.