The Diabetes Control and Complications Trial (DCCT) (NEJM 1993:329:977-86) diabetes therapy with regard to their effects on the development and progression …
Growth Hormone Deficiency After Cushings Disease: By David Cook, MD
Introduction
Adult GH deficiency most often occurs following pituitary surgery or
radiation Whenever pituitary surgery or radiation is performed, there is
a risk that normal secretion of pituitary hormones will be affected Of
all of the pituitary hormones, secretion of GH appears to be the most
easily impaired If a patient is lacking normal secretion of three or four
pituitary hormones, there is a 95 chance that the patient is GH deficient
In patients who have had pituitary surgery or radiation, there is a 25
chance that the patient will be GH deficient even if secretion of other
pituitary hormones is normal Thus, if pituitary surgery or radiation has
been undertaken to cure Cushings disease, GH deficiency should be
evaluated
What is Growth Hormone?
Growth hormone GH is a protein hormone made by the pituitary gland
The pituitary gland not only produces GH, but releases secretes GH into
the bloodstream After entering the bloodstream, GH attaches to most
tissues, especially bones, and results in height increase in children In
children, GH
deficiency results in poor growth and resultant short stature
GH replacement restores normal growth in GH deficient children
Over the last ten years, it has been discovered that adults need GH
as well Like children, adults can be given GH replacement if they are
shown to be deficient The approval by the FDA for adult GH replacement
has been in place for the past 4 years Since adults have already achieved
their genetically determined height, loss of GH does not impact height, but
it does affect the body in many other ways
Growth Hormone Deficiency
The consequences of GH deficiency fall into three categories that
include body changes, blood lipid cholesterol and fat changes, and
psychological/cognitive changes Because GH maintains muscle, bone, and
fat, loss of this hormone results in a decrease in muscle, a decrease in
bone density and an accumulation of fat The decrease in muscle translates
to poor muscle function and decreased exercise capacity The decrease in
bone density, can lead to osteoporosis and increased incidence of
fractures The increase in fat occurs under the skin, but also in the
abdomen
or, more specifically, inside the abdomen as occurs with Cushings
Syndrome This location is referred to as visceral fat Medical science
has discovered that visceral fat accumulation is especially dangerous
because it is associated with an increase in the aging of blood vessels,
referred to as atherosclerosis The increased visceral fat leads to
detrimental changes in the blood lipid levels More specifically, there is
an increase in the bad cholesterol LDL cholesterol and a decrease in
the good cholesterol HDL cholesterol There is also an increase in
blood triglycerides, another circulating fat, which is associated with
premature blood vessel aging GH also effects blood sugar regulation and
unexplained hypoglycemia can be another clinical presentation
The psychological changes associated with GH deficiency have been
well studied Patients who develop GH deficiency seem to lose energy
Loss of energy is often the guiding symptom that prompts further
investigation Many individuals who have undergone surgery or radiation to
the pituitary, particularly those with other hormone deficiencies, realize
that
something is missing Frequently, the missing component turns out to
be GH Many patients do not report feeling poorly, but the patient or
their spouse usually notices a loss of interest in their usual hobbies or
activities or a failure to resume normal activities following pituitary
surgery or radiation A decrease in sociability, referred to as social
isolation, is another symptom Patients suffering with this symptom do not
like to go out and meet with their friends or social acquaintances
Patients with GH deficiency may also experience decreases in cognitive
function, including memory difficulties, as well as mild depression and a
decreased interest in sex If GH deficiency is suspected, and there are
no contraindications, testing for GH should be suggested
Contraindications to GH therapy in adults include an actively growing
tumor There is no evidence that GH increases the rate of tumor growth,
however, if not all of the tumor could be removed during surgery, it is
recommended that the size of the tumor remain stable for a period of 1 year
prior to starting GH replacement Also, following successful
pituitary
surgery, testing for GH deficiency should be delayed 1 year to establish
tumor removal or stability GH does not cause cancer, but it is
recommended that patients who have had cancer be cancer free for 5 years
prior to beginning therapy Another reason for not beginning therapy is
proliferative retinopathy in diabetics Also, GH hormone replacement can
potentially aggravate carpal tunnel syndrome Your individual physician
can best determine if you are a candidate for GH replacement and testing
Diagnosis of Adult GH Deficiency
Although GH circulates in the blood, it is released periodically
and disappears rapidly from the bloodstream due to uptake by the tissues
Because of this, a random blood GH is usually low or undetectable in both
normal and GH deficient patients For this reason, endocrinologists use
blood IGF-1 insulin-like growth factor 1 measurements and a GH
stimulation test to prove deficiency of this hormone Patients with GH
deficiency have low IGF-1 levels compared to normal age and sex matched
controls In patients with no pituitary function, low IGF-1 levels alone
can be
diagnostic, but in most cases a stimulation test will be required
Some patients may have normal IGF-1 and still be GH deficient
There are a number of different GH stimulation tests While these
tests use different compounds or drugs, the common principle is that the
pituitary gland is stimulated to secrete GH Blood GH is then measured
over a period of time, usually two hours, following stimulation Your
physician will pick one of the standard tests The testing is done in the
outpatient setting and you may be instructed not to eat or exercise prior
to the test
Treatment of GH Deficiency
Once a physician has proved GH deficiency, GH replacement therapy
will be started GH is given daily by injection by the patient or a family
member using insulin needles and syringes GH replacement should be
started at a low dose and gradually increased until a final maintenance
dose is reached Slowly increasing the dose at 4-8 week intervals is
required to avoid start up symptoms
The symptoms associated with GH therapy fall into two categories;
those associated with starting or raising the dose of GH and
those
associated with too much GH Start-up symptoms consist of headache,
blurred vision, and muscle and joint pain These symptoms usually appear 7-
10 days after starting GH or raising the dose and disappear by 14 days if
transient If these symptoms persist, the dose should be decreased In my
experience, very few patients elect to give up on treatment If they do
give up therapy, it is usually because they cannot get past the symptoms
associated with beginning or advancing therapy
Symptoms of excess GH are similar to start-up symptoms and consist of
muscle or joint pain and/or carpal tunnel syndrome numbness, tingling, or
shooting pain in the thumb, index and middle finger Growth hormone also
increases water and salt retention and in excess, can cause swelling and
potentially aggravate high blood pressure
If you are a diabetic, your doctor will pay close attention to your
blood sugar levels Initially, GH replacement can aggravate diabetes, but
later improves control Diabetes is not a contraindication to therapy GH
will aggravate diabetes control initially and require a 20-30 increase in
diabetic medication for the first
3-6 months The need for increased
medication usually subsides over the next 6 months
Before beginning therapy, your physician will most likely collect
some baseline information that can be tracked over a period of time The
items I usually track include bone density, body composition percent fat
and lean muscle mass , blood lipid profiles, blood sugar, IGF-1 levels,
height, weight, waist and hip circumference, blood pressure and answers to
an easy to complete quality of life questionnaire These are useful for
showing improvements to patients as well as insurance companies The
starting dose I use for men, women not taking estrogen, or women on
transdermal estrogen is 2 micrograms per kilogram of body weight per day
mcgs/kg/day Women on oral estrogen are started at 4 mcgs/kg/day and
both men and women over 60 years of age are started at no more than 100
micrograms total per day In no case do I start a dose greater than 300
micrograms total per day
Once the patient begins GH therapy, the patient will need to see
their doctor every 4-8 weeks until the correct maintenance dose is
established
To determine the proper dose, the physician will usually
obtain a blood sample for measurement of IGF-1 levels and discuss how the
patient is feeling Low IGF-1 values generally indicate a need for a
higher dose, while high IGF-1 values indicate that the dose is too high
In most cases, the maintenance dose is determined based on patient
tolerance of therapy, rather than absolute IGF-1 concentrations Depending
on the patient, I generally increase the dose in increments of 1-
2mcgs/kg/day except in those over 60 where the increment is a total of 50
micrograms per day The number of dose changes at 4-8 week intervals
needed to reach a maintenance dose is usually 2-4
There is tremendous variability in GH dose requirements in adults,
especially at the extremes of the age groups In my experience, younger
patients in their 20s can require as much as 2000 micrograms per day,
while older patients in their 70s require as little as 80 micrograms per
day Most men and women in the middle age range require 200 - 800
micrograms per day
Please note that the FDA approved, injectable GH that is
prescribed
by a physician is not the same as the health food store GH supplements In
general, health food store GH supplements are without any known benefit
What should the Patient Expect?
Once the maintenance dose is reached, there is usually another 3-4
month period before the full benefits of GH therapy are realized Why does
this take so long? No one knows the answer to this question, but everyone
agrees it takes 9-12 months before the individual experiences full
benefits This is not to say that some symptom improvement may not appear
right away in 2-4 weeks Most patients do feel better in this early time
period Often if the patient or physician asks a spouse how the patient is
doing, the answer will be that the patient is returning to their usual
self The patient, however, is often not able to appreciate the subtle
changes their body is going through If the patient purposely or
inadvertently misses a few doses, they will notice just what GH therapy has
meant to them in their daily lives and quickly return to their daily GH
injection Generally, patients notice an increase in energy, less fatigue,
an increased
ability to exercise, improved cognitive function and a return
to their normal social life Weight loss may not be experienced, but there
is an overall shift towards greater lean muscle mass and loss of abdominal
fat with a resulting improvement in blood lipid levels Bone density
usually takes two years to improve Improvements in the overall quality of
life have been validated using pre and post treatment scores on quality of
life questionnaires and the improvements are often dramatic If you have
had pituitary surgery or radiation and suspect that you may be GH
deficient, complete the quality of life questionnaire inserted in this
newsletter and take this article and the questionnaire to your
endocrinologist You may be pleasantly surprised
Editors Note: Dr Cook is Professor of Medicine at Oregon Health Sciences
University in Portland, Oregon where he has been involved in the diagnosis
and treatment of Cushings since 1969 Dr Cook has also been extensively
involved in the diagnosis and treatment of adult Growth Hormone deficiency
Some of the information in this article was previously published on the
Pituitary Society web page
and in the Magic Foundation Newsletter
Additional Information on Growth Hormone
You can visit the The Pituitary Societys web site at:
wwwpituitarysocietyorg
The Magic Foundation offers information and support services for patients
with Growth Hormone deficiency
wwwmagicfoundationorg
1-800-362-4423
Source:miteam.org
