National Hormone and Pituitary Program: Information for People Treated with Human Growth Hormone (Comprehensive Report)
How did the problem of Creutzfeldt-Jakob Disease (CJD) occur in people who were treated with hGH?
Before scientists learned how to make synthetic hormones, many animal hormones, such as insulin, were used to treat human disorders. Growth hormone (GH) from animals did not work in humans. Human growth hormone (hGH) was made from human pituitary glands by the National Hormone and Pituitary Program (NHPP), funded by the U.S. Public Health Service (PHS). From 1963 to 1985, the NHPP sent hGH to hundreds of doctors across the country. Doctors used the hormone to treat nearly 7,700 children for failure to grow.
In 1985, the PHS learned that three young men treated with hGH died of CJD, a rare and incurable brain disease. The PHS believed these illnesses were related to hGH. PHS doctors immediately stopped distributing the hormone. They began a national study to learn more about how hGH treatment caused this problem. The PHS continues to contact people who have been treated with hGH to provide information to them and to their doctors about health risks linked to hGH.
How many people treated with hGH in the U.S. got CJD?
The Public Health Service has identified 26 cases of CJD among the 7,700 people in the United States who received NHPP hGH. As of October 2005, none of these people began treatment with hGH after 1977, when Dr. Albert Parlow's laboratory began producing NHPP GH and a new purification step was added.
Of the 7,700 people treated with hGH from NHPP, the PHS got the names and addresses of 6,272 from their doctors and treatment centers. We believe there may be another 1,400 people treated with hGH whose names and addresses we do not have. Adding these numbers together, we think that about 7,700 people were treated with hGH. Because treatment centers did not have names and contact information for these people, we did not know about possible deaths in the group of 1,400. We hoped we would learn about CJD and other health problems in these patients from the many doctors we have told about this problem. This has proven true. We learned that 5 of the 26 people with CJD that we know about were among the 1,400 people we were not able to identify and study before. We believe that telling patients and doctors as soon as possible about the CJD problem has helped us learn about all who got CJD so that we can provide that information accurately. We have also learned that five people in New Zealand and one person in Brazil who received U.S.-made hGH also got CJD. All together, 32 people who were treated with hGH made in the U.S. have gotten CJD.
How many people in other countries who were treated with hGH got CJD?
People treated with hGH in other countries also got CJD. We learned this because U.S. Public Health Service doctors share information with doctors around the world about health issues such as CJD. Doctors also read reports about CJD and other health problems related to hGH treatment.
New Zealand has reported 5 people with CJD among 184 who received hGH. All 5 were among 46 people who received hGH made by the U.S. lab that supplied most NHPP hGH before 1977. We don't know why this rate—5 out of 46 (11 percent)—is so high in those who received American hormone. We believe that this U.S.-made hormone did not undergo the same filtering process used in the U.S. when the hormone was put into vials. In addition, some hormone preparations sent to New Zealand were not distributed in the United States.
New Zealand has little information on the hormone preparations these patients got. The five people who got CJD appear to have no period of treatment in common. According to a letter from the New Zealand Ministry of Health, one person who developed CJD was treated from 1965 to 1972, a second from 1966 to 1972, a third from 1964 to 1966, a fourth from 1967 to 1969, and a fifth from 1970 to 1973. With no common period of treatment, it is unlikely that a single preparation exposed all five patients to CJD.
We have some information on the hormone sent to New Zealand from the lab that also produced hormone for the NHPP. Some preparations and components of preparations were used in both countries and others were distributed only in the United States or in New Zealand.
The time between the start of hGH treatment and the first sign of CJD symptoms was similar in the United States (from 14 to 33 years) and New Zealand (from 17 to 32 years). The New Zealand patients who got CJD were treated with hGH for an average of 4 years. In the United States, average treatment time was nearly 9 years in patients who got CJD.
In France, there have been 89 people with CJD among 1,700 treated with hGH. The pattern of exposure to CJD is very different in France than in the United States. In France, people who received hGH in 1984 and 1985 appear to be at highest risk for CJD. We have learned from animal studies that when doctors injected a greater amount of CJD infectious agent into an animal, it took less time for CJD to develop. Because of the larger number of people with CJD and shorter times between treatment and CJD onset in France, the level of infection in French hormone was probably higher than in the U.S. hormone. The purification step used in France was different from the U.S. purification step begun in 1977.
Britain has had 38 people with CJD among 1,848 who received hGH. Experts have also confirmed CJD in two people in Holland, and one each in Australia and Brazil. France, Britain, Holland and Australia made their own hormone. The Brazilian patient got hGH from a U.S. lab that also made NHPP hormone before 1977. This was a different lab than the U.S. lab that made hormone for New Zealand. Four Australian women developed CJD after receiving other pituitary hormones as fertility treatments.
What about other diseases?
Many people treated with hGH also have problems making other pituitary hormones. One pituitary hormone tells the adrenal gland to make cortisol, a hormone necessary for life. People lacking this hormone are at risk of death from adrenal crisis, but this can be prevented. More people treated with hGH have died from adrenal crisis than from CJD. Please read the health alert we’ve provided and discuss this information with your doctor.
Besides CJD, we have not found other serious or fatal health risks from hGH treatment.
"Mad Cow" Disease
In the past few years, reports of a new form of CJD in young people, mostly in Britain, have raised concerns worldwide.
Since at least 1985, cattle in Britain have developed a disease called bovine spongiform encephalopathy (BSE) or "mad cow" disease. "Mad cow" disease is similar to CJD, but "mad cow" disease and CJD are separate diseases. By early September 2002, Britain confirmed that 127 people had developed a "variant" CJD (vCJD). These people apparently ate beef from animals with "mad cow" disease. In the United States, only one case of vCJD has been found, in a young English woman. She lived in Britain when BSE was spreading in cattle and probably was infected then.
People who received hGH are not at higher risk for vCJD.
HIV, also known as the human immunodeficiency virus, causes AIDS. hGH does not cause AIDS. HIV is destroyed by the methods used to make hGH. People who have been treated with hGH do not have a higher risk for AIDS.
Deficient GH in Adults
Some people who received hGH as children may have low levels of GH as adults. Symptoms vary, but may include:
- more body fat
- less muscle
- less bone mass
- less strength
- less energy
If you have these problems ask your doctor whether they might be due to low GH. Since these conditions are common in lots of people, they are not always due to low amounts of GH. Studies have shown that GH administration in adults with low GH results in reductions in fat and increments in muscle mass. Effects on strength, energy and bone fractures in GH-deficient adults receiving GH replacement are not as clear.
Today GH is completely synthetic. It poses no threat of contamination. The Human Growth Foundation is one source of information about growth-related disorders. The Foundation can be reached at 1–800–451–6434.
Researchers recently reported two people treated with hGH in Britain developed colon cancer. Two U.S. patients who received hGH also died of colon cancer. Such a small number of reports is not enough for us to say if there really is an increased colon cancer risk for all people treated with hGH. We ask you to report colon cancer if it occurs to help us better understand if there is increased risk. We have asked the Food and Drug Administration and the pharmaceutical companies that make biosynthetic GH (bGH) to watch for colon cancer in people treated with bGH.
Previously we reported that doctors in Japan found an increased risk of leukemia in people treated with hGH. When we contacted all families in 1988, we found no increased risk of cancer in those who did not have tumors before hGH treatment. Many people who received NHPP hGH had brain tumors that caused their lack of hGH. People who have had one tumor have an increased risk for getting other tumors. Later studies from Japan and a new report from Britain also found no increased risk of leukemia in those without previous tumors.
Many people who received NHPP hGH had brain tumors that caused their lack of GH. People who have had one tumor have an increased risk for getting other tumors. Our studies of people who received NHPP hGH show no higher overall risk of death from cancer than is seen in the general population in those who did not have tumors before hGH treatment. We will continue to follow the health of those treated with NHPP hGH so that we can provide you with the best information possible.
What about other problems?
We have no evidence that hGH causes changes in personality, emotional problems, or suicide.
What are the early symptoms of CJD?
CJD does not cause the same symptoms in everyone. In most people treated with hGH, the first signs of CJD were difficulty with walking, dizziness, clumsiness, and problems with balance. Later, a person with CJD may begin to slur words, lose muscle control, or have problems with vision, memory, or thinking. Once symptoms begin, CJD usually gets worse quickly. Within 2 to 3 months, patients could not walk or do other simple tasks.
Headaches are not a symptom of CJD. Mild symptoms that come and go over a long time, such as feeling clumsy, irritable, or forgetful, probably do not mean that you have CJD. You should discuss concerns with your doctor if you are not sure.
CJD is a rare disease, and most cases of CJD are not linked to hGH. When CJD is not linked to hGH, the first symptoms are usually mental changes such as confusion, problems thinking, memory loss, behavior changes, and dementia. Though symptoms may differ, there are similar changes in the brain tissue of all patients with CJD.
What is my risk for getting CJD?
No one can say what an individual person's risk is. Of the approximately 7,700 people who received NHPP hGH, 26 people got CJD. The two greatest risk factors are how long a person was treated, and when the person was treated.
How long a person was treated:
When a person was treated:
- In the United States, the average length of time for hGH treatment was about 3 years. For the people who later got CJD, the average length of treatment was about 9 years.
- Even though the longer treatment time increased the risk for CJD in the U.S., in other countries CJD has developed after shorter treatment periods.
- There is still no CJD in Americans who began treatment after new methods of purifying hormone began in the United States in 1977.
- A purification step used to make NHPP hGH after 1977 greatly reduced and may have gotten rid of possible CJD infection.
- No CJD has been reported in people who were treated with commercial hGH from human pituitaries. The new preparation step used after 1977 by the NHPP was also used for commercial hGH.
- It can take 30 years or more for a person to develop CJD. This means that more time must pass before we know if someone who began treatment after 1977 could still develop CJD. With each year that goes by with no CJD in people who only received the newer hormone, we are more encouraged about the safety of hGH.
- Overall, one person out of about 300 people or 26 out of 7,700 people who were treated with hGH in the U.S. got CJD.
- Not all who received hGH are at equal risk. The risk in those who began treatment before 1977 is about 1 in 104 people or a little less than 1 percent.
- People who started treatment before 1970 are at higher risk. In that early group, 1 in 52 people got CJD (about 2 percent of the early group). Because there was no new CJD in the past 5 years in those who began treatment before 1970, we hope that these patients may be moving out of the incubation period for CJD. However, it is still too soon to be sure whether there will be additional reports of CJD in this group.
- The longest time from the start of hGH treatment to first signs of CJD is 33 years in U.S. patients, according to reports. One person in Holland got CJD attributed to hGH 38 years after a very brief use of hGH. Research studies tell us that the time it takes to get CJD depends, in part, on how much infectious material is given and how it is given. The disease generally takes longer to develop when a small amount of infectious material is given. The patient in Holland with the long incubation time received a very brief exposure to hGH.
When was I treated and for how long?
The best person to give you details on your treatment is the doctor who gave you hGH or a doctor who has access to your treatment records. To protect patients' privacy, the PHS did not ask for the names of those treated with hGH until 1985, when we learned of CJD. In 1985, we asked doctors and treatment centers for names and addresses so we could inform them of the risk of CJD.
We know which hGH preparations were sent to each treatment center and when they were sent. But because individual doctors administered the hGH, we don't know which preparation each person might have gotten. We have tried to find this information in medical records of patients who developed CJD. But many doctors did not note the preparation in their records. When records were incomplete, we had to assume that patients who got CJD might have been exposed to all preparations sent to their treatment center during the time they were treated. Since we cannot confidently identify high-risk or risk-free hormone, we do not think that details on the hormone preparations you got will help clarify your level of risk. If you still wish to learn which preparations you received, the doctor who treated you is the best person to tell you about your treatment.
Which hormone preparations caused CJD?
We have not found any particular preparation of hGH that is especially likely to carry CJD. We believe that CJD did not come from a single infected pituitary gland or preparation. Prior to 1977, in an effort to extract as much hormone as possible from pituitaries, the pituitaries were often processed repeatedly. Hormone extracted from the same pituitaries was often included in many hormone preparations. Also, patients who got CJD were treated on average for nearly 9 years and received many different hormone preparations. This makes it very difficult to identify any preparation associated with transmitting CJD.
Animal research: In 1985, the PHS tested all available preparations of NHPP hGH in animals. Doctors wanted to see if a specific preparation could transmit CJD. If an animal got sick with CJD, it clearly had received hormone with the CJD infectious agent. However, we don't know if CJD contamination was spread evenly among all vials of hGH. It's possible that one vial got more contamination and another got little or none from the same lot of hGH.
To shorten the time for animals to get CJD to less than 3 years, hGH was injected into the brains of test animals. The animals were watched for 10 years. The brains of all animals were examined for signs of CJD.
Results: Only one animal developed the disease 5 ½ years after injection of hormone. Two other animals that received different vials of the same hormone preparation did not develop CJD. None of the people who developed CJD are known to have received the hormone that made the animal sick. At most, two patients (whose records are incomplete) may have received this hGH preparation. Because of this, we do not believe that the patients who received the hormone preparation that transmitted CJD to the animal have a greater risk of developing CJD than others treated with hGH. We continue to analyze the hGH preparations received by patients who got CJD in an attempt to identify infected preparations. However, we believe that multiple preparations of hGH probably had very low levels of the CJD infectious agent. With such low levels of contamination, some vials of a preparation might carry CJD while other vials would not.
If I have CJD can I pass it to my spouse or children?
- Scientists do not believe that CJD is transmitted through casual contact or sexual contact.
- Spouses and children of patients with CJD are not at increased risk.
- Except for rare genetic forms of CJD, a pregnant woman does not pass CJD on to her child.
- CJD from hGH does not affect the genes and is not passed on to future generations.
Is there a test to predict if I will get CJD?
Although researchers are trying to develop a test that will predict who might get CJD, there is currently no test that can identify who will or will not get CJD. There are variations in the structure of the gene for the brain protein that becomes abnormal in CJD. These differences may make some people more likely to get CJD than others. While a person's genetics may affect the risk of CJD, researchers cannot accurately predict the risk of developing CJD in individuals from genetic or other tests.
Why can't I donate blood or organs?
There have been two reports of the agent that causes variant CJD (vCJD) being transmitted through blood. Variant CJD is the disease that occurs in people who ate tainted beef or were exposed to products from cattle with “mad cow” disease. Variant CJD is different from the classic type of CJD that occurred in hGH recipients. We do not know if the type of CJD that occurred in GH recipients can be transmitted by blood. Nevertheless, doctors want to be especially careful because there is no test they can use to screen blood supplies.
Until we know more, the following people should not donate blood:
- Anyone who was treated with pituitary hGH. People who have been treated only with biosynthetic GH, in use since 1985, can donate blood.
- Relatives of patients with CJD. It is important to prevent donation by people from families with rare genetic forms of CJD. They could harbor CJD even if they do not have symptoms. Family members of people treated with hGH are not affected by this policy and can donate blood.
- Those who lived in Europe when cattle products may have spread the agent responsible for vCJD.
How is CJD diagnosed?
CJD is usually diagnosed based on signs and symptoms of the illness, how severe they are, and how quickly they become worse. Laboratory test results can suggest CJD as well. However, doctors must study brain tissue from a biopsy or autopsy in order to diagnose CJD for sure. In 1996, researchers developed a test that helps doctors diagnose CJD in patients with symptoms. This test detects an abnormal protein in a sample of spinal fluid. When this protein is found it helps make a diagnosis of CJD. It is much easier and safer to take a sample of spinal fluid than to do a brain biopsy. Unfortunately, this test cannot identify CJD in patients who do not have symptoms. The test cannot predict who may develop CJD in the future.
British researchers recently reported success using magnetic resonance imaging (MRI) to diagnose variant CJD in people with symptoms of the disease. MRI is a safe and painless tool that does not take brain or spinal fluid samples. (See Zeidler M, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet. 2000; 355:1412–1418 online or at a medical library.)
What does research tell us about CJD?
- Although CJD is a rare disorder, some of the world's leading researchers are working hard to learn more about this disease. The most common type of CJD occurs all over the world and is very rare. Only one in a million people develop CJD per year. Most people who develop CJD get it after age 55.
About 10 percent of the people who get CJD have inherited it. Some people have gotten CJD from medical procedures such as hGH injections, tissue grafts, or corneal transplants. Scientists don't fully understand what causes CJD. Evidence suggests that a unique infectious agent called a prion [pree'-on] may be the cause. A prion is an unusual infectious agent because it contains no genetic material. It is a protein that takes on different forms. In its normal, harmless form the protein is curled into a spiral. In its infectious form, the protein folds into an abnormal shape. Somehow, these abnormal proteins change the shape of normal proteins. This change begins a serious chain reaction that results in brain problems.
People with inherited CJD have an abnormal gene that leads to changes in their prion protein. This gene makes the protein likely to assume the abnormal shape. Exposure to the abnormal form of the protein can also occur through injection of contaminated hGH, tissue grafts, corneal transplants, or other exposures to infected brain tissue.
If CJD results from a defect in protein folding, it may be possible to identify drugs that can help the prion protein assume its proper shape. Such drugs would slow or stop the progress of the disease. Treatments like these are being studied in animal models and early clinical trials. Researchers both in Europe and the U.S. are trying to develop a test that will identify CJD before symptoms appear. The NIH spent approximately $17.7 million on CJD research in Fiscal Year 2001.
These medical journal articles provide more information about CJD:
Why should people treated with hGH know about CJD?
Many people treated with hGH were children when the problem of CJD came to light. They are now adults. Some parents did not want to burden their adult children with news about CJD. However, in our updates, we have consistently stressed that parents should discuss the risk of CJD with their sons and daughters as they get older. This subject is painful to discuss, but it is more upsetting for adults to learn about their risk of CJD from the media or when they try to donate blood. In addition, if parents are no longer available to receive these mailings, their adult children may have no access to important new information the PHS may learn. If you are the parent of an adult who is not getting these mailings, please provide your child's address to us so we can send this information to them also. We are glad to answer any questions they may have.
How can I get support and information?
To contact us, please call the toll-free number, 1–800–472–0424. A recording will ask you to leave your name, phone number, and a good time to reach you. A staff member will call you back promptly. You can also call, write, or have your doctor contact us at the above address or by email at NIDDK.Inquiries@nih.gov.
We have a web site at www.endocrine.niddk.nih.gov/pubs/creutz/creutz.htm. The site contains this update and a list of articles of interest to people treated with hGH. The web site is updated when we get new information. We will mail updates in the future only when there is major new information. Some examples would be:
- discovery of a diagnostic test for non-symptomatic CJD
- development of preventive therapy or treatment for CJD
- if there are any reports of CJD in people who began treatment after 1977
We will continue to post information about new reports of CJD and other new information on our web site. If you do not have access to the Internet, we will mail this information to anyone who requests it.
The Human Growth Foundation (HGF) is a nonprofit organization concerned with children's growth disorders and adult GH deficiency. HGF has published a brochure on adult GH deficiency. To obtain a copy, call 1–800–451–6434. The HGF also supports an Internet mailing list to help the exchange of information about adult hGH deficiency and adult hGH replacement therapy. To subscribe, follow the instructions on the HGF web page at www.hgfound.org.
The Creutzfeldt-Jakob Disease Foundation Inc. (www.cjdfoundation.org/) was created in 1993 by two families who lost relatives to CJD and the neurologist who treated the patients. This nonprofit corporation seeks to promote research, education, and awareness of CJD and to reach out to people who have lost loved ones to this illness. For information on CJD from the NIH, see www.ninds.nih.gov.
How can I help with the follow-up study?
Those who got hGH, their families, and their doctors can help researchers understand more about CJD and the health problems of people treated with hGH. Information from you helps us keep everyone informed about new developments. It is most important for PHS doctors to know if CJD is suspected or diagnosed in someone who received hGH. Also, we ask that family members or doctors notify us of deaths from any cause in people who received hGH. When your family allows PHS doctors to review the medical records of a family member who has died, you add to a growing knowledge base that may benefit thousands of people.
As before, we ask that you let us know your current address (and email address, if you have one) in case we need to contact you with new information. To report health information, please contact:
National Institutes of Health
NIDDK Office of Communications and Public Liaison
Building 31 Room 9A06
31 Center Dr MSC 2560
Bethesda, MD 20892–2560
Finally, we want you to know that scientists at the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention continue to actively study this problem. They are available to answer your questions.
National Endocrine and Metabolic Diseases Information Service
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Bethesda, MD 20892–3569
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