Study of Growth Hormone Treatment and Creutzfeldt-Jakob Disease Underscores Need for Prevention of Adrenal Crises
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
A larger number (59) died from adrenal crisis, a sometimes-fatal
complication that can be prevented if it is recognized and treated
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."