Growth Hormone and Mortality in Prader-Willi Syndrome
Abstract – Phillip D. K. Lee, MD, FAAP, FACE
www.GGHjournal.com June 2006
The administration of growth hormone (GH) has numerous
benefits for individuals with PWS including a decline in the fat percentage of
lean body mass, and improvement in body composition, agility, and muscle
strength. In the almost 20 years since the introduction of the usage of GH in
PWS, very few bad effects have been reported. However, 2 children with PWS who
were receiving GH died in 2002. This led to a discussion about the safety of GH
in PWS and ultimately resulted in the drug company Pfizer applying a warning
label to its GH prescriptions. This warning was very stern and stated that GH
should not be used in those with PWS who are severely obese or have severe
breathing problems. In 2004, other drug companies added the same warning to
their GH drugs. This led to a tremendous amount of concern in the PWS community,
as denying GH to individuals with PWS can be very damaging to their health and
lifestyle.
In this paper, Lee, a respected and knowledgeable
endocrinologist who specializes in PWS, describes the known cases of deaths
related to GH in PWS and discusses in detail this controversial topic. The
question of death being increased due to GH therapy is a very important one, but
it is very difficult to answer largely because there is not enough data to make
a satisfactory statistical analysis.
Unfortunately, premature death in PWS has been a problem
since long before GH was used as a treatment. Deaths are often due to
cardio-respiratory illness, and none of the reported 190 deaths reported to PWSA
(USA) since 1977 appear to be related to GH. Since May of 2006, 18 children and
2 adults worldwide with PWS died while receiving GH. Some of these deaths were
due to causes completely unrelated to GH, such as drowning in a bathtub. Many of
the deaths were in individuals who were significantly overweight, and almost all
of the cases were not receiving the dose on the medication’s label.
Some have suggested that GH can cause death in individuals
with PWS with breathing problems. For individuals who appear to have died
because of severe breathing problems, it is noted that these problems were
present before GH treatment even began. In 5 out of 6 cases examined cases of
those with breathing problems, GH treatment did not make these types of
conditions worse. Lee states (see below) that special analysis of sleep problems
need not be standard for every individual being treated with GH. However, if an
individual has a history of excessive daytime sleepiness or extreme breathing
problems during sleep, he recommends a sleep analysis before GH treatment.
Lee feels the concerns about GH and death in PWS are
ultimately not valid and concludes with the following main points: 1) deaths in
infants with PWS are usually due to feeding aspiration, have nothing to do with
GH treatment and should be closely monitored; 2) deaths in older children and
adults with PWS are very often associated with obesity, and the insulin
resistance associated with obesity may be increased by GH; this deserves special
attention; 3) tub-drowning deaths have nothing to do with GH and should be
addressed separately; 4) most of the deaths during GH treatment occurred with
doses below the recommended amount; doses should not be limited and should be
well-monitored; 5) clinical follow-up is crucial to preventing deaths which are
attributed to GH treatment, as almost all of the reported deaths occurred within
the first 18 months of treatment; and 6) sleep analysis should not be required
for GH treatment unless the patient has an outstanding history of breathing
problems which merit further examination before treatment begins. (This
opinion is not held by most PWS experts who believe a sleep study should be
done. See the PWSA (USA) precautions article.)
GH as a treatment for those with PWS has led to
improvements in height and appearance in addition to providing what Lee calls “a
new outlook on life.” Further population studies and more thorough follow-up
with patients will add to our knowledge of GH and will lead to a better
understanding of how to best administer GH while sparing the seemingly
unnecessary association between deaths in PWS and this life-altering treatment.
Abstracted by: Mayim Chaya Bialik, Ph.D
edited:
03/23/2010
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