Acromegaly is caused by prolonged
overproduction of GH by the pituitary gland. The pituitary is a
small gland at the base of the brain that produces several
important hormones to control body functions such as growth and
development, reproduction, and metabolism. GH is part of a
cascade of hormones that, as the name implies, regulates the
physical growth of the body. This cascade begins in a part of
the brain called the hypothalamus, which makes hormones that
regulate the pituitary. One of these, growth hormone-releasing
hormone (GHRH), stimulates the pituitary gland to produce GH.
Another hypothalamic hormone, somatostatin, inhibits GH
production and release. Secretion of GH by the pituitary into
the bloodstream causes the production of another hormone, called
insulin-like growth factor 1 (IGF-1), in the liver. IGF-1 is the
factor that actually causes the growth of bones and other
tissues of the body. IGF-1, in turn, signals the pituitary to
reduce GH production. GHRH, somatostatin, GH, and IGF-1 levels
in the body are tightly regulated by each other and by sleep,
exercise, stress, food intake and blood sugar levels. If the
pituitary continues to make GH independent of the normal
regulatory mechanisms, the level of IGF-1 continues to rise,
leading to bone growth and organ enlargement. The excess GH also
causes changes in sugar and lipid metabolism and can cause
The excess of growth hormone in your bloodstream can affect
various tissues in your body which can make them 'thicken' or
'grow'. So, over time one or more of the following may develop:
- Hands and feet become larger and broader. Your glove and
shoe size may increase over the years. You may not be able to
get a wedding ring off.
- The skin may thicken (particularly on the face) and become
more greasy and sweaty.
- Changes to the face which may include: thickened lips and
nose, thickening of the scalp, the jaw becoming more
prominent. As the changes develop slowly, they may not be
recognised by family or friends. But, looking back at old
photographs may suggest your facial appearance has 'thickened'
- The vocal cords thicken which may cause your voice to
- Your tongue may enlarge so you may often 'bite your
- Thickening of cartilage may cause arthritis in various
- Thickening of the nasal passages can make you snore loudly
and may cause obstruction in airflow when you are asleep
(sleep apnoea). This can make you have a poor nights sleep
with daytime drowsiness.
- 'Carpel tunnel syndrome'. This is where a nerve going
through the wrist is squashed by thickened tissue. It can
cause pain, tingling and weakness in parts of the hands.
Other effects of too much growth hormone include
- General tiredness and some muscle weakness.
- About 1 in 5 people with acromegaly also develop diabetes
as growth hormone counters the effects of insulin.
- High blood pressure develops in about 1 in 3 cases.
- Increase risk of heart disease and stroke. This is
probably because of the increase risk of developing high blood
pressure and diabetes.
- The risk of developing cancer of the bowel may be slightly
Also, in about 1 in 3 cases, the adenoma also makes too much
of another hormone called prolactin. This can cause sexual and
menstrual problems, and a milky discharge from the nipple. Many
men with acromegaly also develop erectile dysfunction
Symptoms caused by the growing tumour
In many cases the tumour remains small and does not cause
pressure symptoms. But, in some cases the tumour grows enough to
cause pressure on the nearby tissues. This can lead to:
- Problems with vision. The tumour may press on the optic
nerves (the nerves going from the eyes to the brain) which are
just next to the pituitary.
- Other normal cells in the pituitary may become squashed
and damaged. So, you may develop a lack of other hormones
normally made by the pituitary. This can cause an underactive
thyroid gland and/or an underactive adrenal gland which can
cause various other symptoms.
Other symptoms in children
If you have too much growth hormone before you finish growing
then you get a condition called gigantism. In this condition you
grow very tall.
Who gets acromegaly?
Acromegaly is rare. About 4 or 5 people in a million develop
acromegaly each year in the UK. It mainly affects adults between
the ages of 30 and 50. Men and women are equally affected.
Rarely, it affects children.
How is acromegaly diagnosed?
- A blood test can measure the level of growth hormone. But,
a single test is not reliable. The diagnosis of acromegaly is
made by a glucose tolerance test. In this test you drink a
sugar drink containing 75 gram glucose. You then have a series
of blood tests over two hours. The glucose should lower the
blood level of growth hormone, but in acromegaly the growth
hormone level remains high.
- A blood test to measure the level of IGF-I (see above) may
be measured if acromegaly is suspected. This may also be used
as an index of disease activity to assess how well treatment
- An MRI scan (magnetic resonance imaging scan) or CT scan
(computed tomography scan) can show the size of the tumour.
- Eye and visual tests will assess if the tumour is pressing
on the optic nerve.
- If you are confirmed as having acromegaly, other tests
will be needed to see if the tumour is causing a lack other
hormones made by the pituitary.
In over 90 percent of acromegaly patients, the overproduction
of GH is caused by a benign tumor of the pituitary gland, called
an adenoma. These tumors produce excess GH and, as they expand,
compress surrounding brain tissues, such as the optic nerves.
This expansion causes the headaches and visual disturbances that
are often symptoms of acromegaly. In addition, compression of
the surrounding normal pituitary tissue can alter production of
other hormones, leading to changes in menstruation and breast
discharge in women and impotence in men.
There is a marked variation in rates of GH production and the
aggressiveness of the tumor. Some adenomas grow slowly and
symptoms of GH excess are often not noticed for many years.
Other adenomas grow rapidly and invade surrounding brain areas
or the sinuses, which are located near the pituitary. In
general, younger patients tend to have more aggressive tumors.
Most pituitary tumors arise spontaneously and are not
genetically inherited. Many pituitary tumors arise from a
genetic alteration in a single pituitary cell which leads to
increased cell division and tumor formation. This genetic
change, or mutation, is not present at birth, but is acquired
during life. The mutation occurs in a gene that regulates the
transmission of chemical signals within pituitary cells; it
permanently switches on the signal that tells the cell to divide
and secrete GH. The events within the cell that cause disordered
pituitary cell growth and GH oversecretion currently are the
subject of intensive research.
In a few patients, acromegaly is caused not by pituitary
tumors but by tumors of the pancreas, lungs, and adrenal glands.
These tumors also lead to an excess of GH, either because they
produce GH themselves or, more frequently, because they produce
GHRH, the hormone that stimulates the pituitary to make GH. In
these patients, the excess GHRH can be measured in the blood and
establishes that the cause of the acromegaly is not due to a
pituitary defect. When these non-pituitary tumors are surgically
removed, GH levels fall and the symptoms of acromegaly improve.
In patients with GHRH-producing, non-pituitary tumors, the
pituitary still may be enlarged and may be mistaken for a tumor.
Therefore, it is important that physicians carefully analyze all
"pituitary tumors" removed from patients with acromegaly in
order not to overlook the possibility that a tumor elsewhere in
the body is causing the disorder.
The goals of treatment are to reduce GH production to normal
levels, to relieve the pressure that the growing pituitary tumor
exerts on the surrounding brain areas, to preserve normal
pituitary function, and to reverse or ameliorate the symptoms of
acromegaly. Currently, treatment options include surgical
removal of the tumor, drug therapy, and radiation therapy of the