Study
Of Growth Hormone Treatment And Creutzfeldt-Jakob Disease Underscores
Need For Prevention Of Adrenal Crises
Source : National Institute Of Child Health And
Human Development / Date : 2004-04-07
The largest study of its kind, designed to track the development
of Creutzfeldt-Jakob disease in people who received human growth
hormone from cadavers, has found that the vast majority of those
who received the hormone did not contract the fatal condition.
However, some recipients (26 out of approximately 7,700) did
develop the disease.
A
larger number (59) died from adrenal crisis, a sometimes-fatal
complication that can be prevented if it is recognized and treated
promptly.
Adrenal
crisis does not affect all patients who require growth hormone,
but may occur in a subgroup of patients whose pituitary gland
fails to make not only growth hormone but also the hormone needed
to regulate the adrenal glands.
Human
growth hormone is now manufactured synthetically, and the synthetic
form does not transmit Creutzfeldt-Jakob Disease (CJD). The
study tracks individuals who received cadaver-derived human
growth hormone, to determine their risk of developing CJD and
to observe their health status.
The
federal study's findings appear in the April Journal of Pediatrics.
It was conducted by scientists at several agencies in the U.S.
Department of Health and Human Services (HHS). At the National
Institutes of Health, researchers from the National Institute
of Child Health and Human Development, the National Institute
of Neurological Disorders and Stroke, and the National Institute
of Diabetes and Digestive and Kidney Diseases, took part in
the study. Researchers from two other HHS agencies, the U.S.
Food and Drug Administration and the Centers for Disease Control
and Prevention, also participated, as did the research corporation
Westat.
Growth
hormone deficiency results from a failure of the pituitary gland
to make sufficient amounts of the hormone, explained the study's
principal author, James L. Mills, M.D., chief of the Pediatric
Epidemiology Section of the National Institute of Child Health
and Human Development (NICHD). Individuals who lack growth hormone
are abnormally short. Growth hormone is also needed to maintain
normal blood sugar; its absence may result in potentially fatal
drops in blood sugar (hypoglycemia).
According
to the 1994 Utah Growth Hormone Study, growth hormone deficiency
occurs in 1 out of every 3,480 children. Patients who can't
make their own growth hormone may also lack other hormones produced
by the pituitary, including the hormone that regulates the adrenal
glands, Dr. Mills added. The adrenals, located atop the kidneys,
secrete cortisol, a hormone that protects the body in stressful
situations. In times of illness or other stress, individuals
who lack adrenal hormones are subject to an adrenal crisis —
a potentially fatal loss of salts and fluids. However, an adrenal
crisis can be treated and sometimes prevented with the drug
hydrocortisone. Treatment for an adrenal crisis may be given
in either tablet form or by injection. In addition to those
whose pituitaries fail to make the proper hormone to regulate
the adrenal glands, adrenal crisis may also result from other
medical conditions.
From
1963 to 1985, the National Hormone and Pituitary Program (NHPP)
supplied human growth hormone to individuals who needed it.
Because synthetic human growth hormone wasn't available at the
time, it was necessary to extract the hormone from the pituitaries
of cadavers. But in 1985, researchers learned that the cadaver-derived
hormone could transmit CJD, a fatal disease affecting the brain,
and halted distribution of the hormone. Information for people
treated with growth hormone from the NHPP is available at http://www.niddk.nih.gov/health/endo/pubs/creutz/updatecomp.htm#5
.
The
current federal study began in 1985. Of the approximately 7,700
people in the United States who received cadaver-derived hormone
from the NHPP, 26 died of CJD. It is also possible that more
deaths from CJD will occur in this group in the future. Dr.
Mills said some studies indicate that CJD may take 30 years
or more to develop.
The
study authors noted that patients who lacked only growth hormone
and had no underlying medical problem but produced normal amounts
of other pituitary hormones had a death rate that was comparable
to what would be expected in a general population of people
in the same age group. However, individuals who lost the ability
to produce other pituitary hormones — often because of
tumors or brain injury — had higher death rates.
Of
the approximately 7,700 people who received the hormone from
the NHPP, 6,107 took part in the current study. Of these, 1,419
required therapy to replace their adrenal hormones. There were
59 deaths from adrenal crisis in this group. Many of the circumstances
surrounding the individuals' deaths are not known, Dr. Mills
said. Some patients were simply found dead. A possible factor
in these deaths could be the age of those who died, Dr. Mills
added. Many were adolescents and young adults, an age group
that may tend to ignore health concerns and take risks.
In
addition, a major symptom of an adrenal crisis, vomiting, might
also interfere with successful treatment. The study authors
wrote that the vomiting might make it impossible to keep the
hydrocortisone tablets in the stomach long enough for them to
take effect.
Dr.
Mills said that one option patients and their physicians might
consider is to have a needle and syringe available for emergencies,
so that the patient or a family member might inject the hydrocortisone
whenever vomiting occurs. He added that many of the deaths occurred
after relatively mild illnesses, such as colds and pneumonia.
Even such minor stresses require patients to take higher doses
of hydrocortisone.
According
to a health alert by the National Institute of Diabetes and
Digestive and Kidney Diseases, symptoms of a cortisol shortage
are feeling weak, feeling tired all the time, feeling sick to
one's stomach, vomiting, no appetite, and weight loss. "When
someone with adrenal gland problems has weakness, nausea, or
vomiting, that person needs immediate emergency treatment to
prevent adrenal crisis and possible death." The health
alert is available at http://www.niddk.nih.gov/health/endo/pubs/creutz/alert.htm
.
The
study authors wrote: "Our data underscore the need to initiate
therapy promptly: of the 35 subjects found dead or comatose
by families or friends, 30 (86%) probably died from unrecognized
or inadequately treated adrenal insufficiency."
Other
deaths resulted from problems not associated with pituitary
hormone deficiencies. Many children died from the underlying
conditions, such as brain tumors, that caused them to be growth
hormone deficient. Similarly, there were 20 deaths from seizures
among patients who did not appear to have adrenal insufficiency.
Dr. Mills explained that these seizure deaths might have resulted
from complications of brain tumors or brain injury.
Two
study participants died of colon cancer. However, the authors
wrote, these cases did not appear to be related to the use of
growth hormone, despite the results from a smaller British study
suggesting that growth hormone recipients had an increased risk
of death from colon cancer. One patient from the current study
had a hereditary form of polyposis, which increases the risk
for colon cancer.
"The
second patient had received radiation treatment for a brain
tumor, which may have had an influence on the development of
colon cancer," Dr. Mills said. "These results do not
support the earlier study's finding that growth hormone was
associated with an increased risk of death from colon cancer."
Editor's
Note: The original news release can be found here .This story
has been adapted from a news release issued by National Institute
Of Child Health And Human Development.
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