Acromegaly

National Endocrine and Metabolic Diseases Information Service

What is acromegaly? puberty, so the excessive GH production in

adults does not result in increased height.
Acromegaly is a hormonal disorder that
However, prolonged exposure to excess
results from too much growth hormone (GH)
GH before the growth plates fuse causes
in the body. The pituitary, a small gland in
U.S. Department increased growth of the long bones and
the brain, makes GH. In acromegaly, the
of Health and thus increased height. Pediatricians may
Human Services pituitary produces excessive amounts of GH.
become concerned about this possibility if a
Usually the excess GH comes from benign, or
child’s growth rate suddenly and markedly
NATIONAL noncancerous, tumors on the pituitary. These
increases beyond what would be predicted
INSTITUTES benign tumors are called adenomas.
OF HEALTH by previous growth and how tall the child’s
Acromegaly is most often diagnosed in parents are.
middle-aged adults, although symptoms
can appear at any age. If not treated, acro­ What are the symptoms of
megaly can result in serious illness and
premature death. Acromegaly is treatable acromegaly?
in most patients, but because of its slow The name acromegaly comes from the
and often “sneaky” onset, it often is not Greek words for “extremities” and
diagnosed early or correctly. The most “enlargement,” reflecting one of its most
serious health consequences of acromegaly common symptoms––the abnormal growth
are type 2 diabetes, high blood pressure, of the hands and feet. Swelling of the
increased risk of cardiovascular disease, hands and feet is often an early feature,
and arthritis. Patients with acromegaly with patients noticing a change in ring or
are also at increased risk for colon polyps, shoe size, particularly shoe width. Gradu­
which may develop into colon cancer if ally, bone changes alter the patient’s facial
not removed. features: The brow and lower jaw pro­
trude, the nasal bone enlarges, and the
When GH-producing tumors occur in teeth space out.
childhood, the disease that results is called
gigantism rather than acromegaly. A Overgrowth of bone and cartilage often
child’s height is determined by the length leads to arthritis. When tissue thickens,
of the so-called long bones in the legs. In it may trap nerves, causing carpal tun­
response to GH, these bones grow in length nel syndrome, which results in numbness
at the growth plates—areas near either and weakness of the hands. Body organs,
end of the bone. Growth plates fuse after including the heart, may enlarge.
Other symptoms of acromegaly include which stimulates the pituitary gland to
• joint aches produce GH.
• thick, coarse, oily skin Secretion of GH by the pituitary into the
• skin tags bloodstream stimulates the liver to produce
another hormone called insulin-like growth
• enlarged lips, nose, and tongue
factor I (IGF-I). IGF-I is what actually
• deepening of the voice due to enlarged causes tissue growth in the body. High
sinuses and vocal cords levels of IGF-I, in turn, signal the pituitary
• sleep apnea—breaks in breathing
to reduce GH production.
during sleep due to obstruction of

The hypothalamus makes another hormone

the airway

called somatostatin, which inhibits GH

• excessive sweating and skin odor production and release. Normally, GHRH,
• fatigue and weakness somatostatin, GH, and IGF-I levels in the
• headaches body are tightly regulated by each other
and by sleep, exercise, stress, food intake,
• impaired vision and blood sugar levels. If the pituitary
• abnormalities of the menstrual cycle continues to make GH independent of the
and sometimes breast discharge in normal regulatory mechanisms, the level
women of IGF-I continues to rise, leading to bone
• erectile dysfunction in men overgrowth and organ enlargement. High
levels of IGF-I also cause changes in glu­
• decreased libido
cose (sugar) and lipid (fat) metabolism and
can lead to diabetes, high blood pressure,
What causes acromegaly? and heart disease.
Acromegaly is caused by prolonged over­
production of GH by the pituitary gland. Pituitary Tumors
The pituitary produces several important In more than 95 percent of people with
hormones that control body functions such acromegaly, a benign tumor of the pituitary
as growth and development, reproduction, gland, called an adenoma, produces excess
and metabolism. But hormones never seem GH. Pituitary tumors are labeled either
to act simply and directly. They usually micro- or macro-adenomas, depending on
“cascade” or flow in a series, affecting their size. Most GH-secreting tumors are
each other’s production or release into the macro-adenomas, meaning they are larger
bloodstream. than 1 centimeter. Depending on their
location, these larger tumors may compress
GH is part of a cascade of hormones that, surrounding brain structures. For example,
as the name implies, regulates the physical a tumor growing upward may affect the
growth of the body. This cascade begins optic chiasm—where the optic nerves
in a part of the brain called the hypothala­ cross—leading to visual problems and
mus. The hypothalamus makes hormones vision loss. If the tumor grows to the side,
that regulate the pituitary. One of the hor­ it may enter an area of the brain called
mones in the GH series, or “axis,” is growth the cavernous sinus where there are many
hormone-releasing hormone (GHRH), nerves, potentially damaging them.

2 Acromegaly
Compression of the surrounding normal Most pituitary tumors develop spontane­
pituitary tissue can alter production of ously and are not genetically inherited.
other hormones. These hormonal shifts They are the result of a genetic alteration
can lead to changes in menstruation and in a single pituitary cell, which leads to
breast discharge in women and erectile increased cell division and tumor forma­
dysfunction in men. If the tumor affects tion. This genetic change, or mutation, is
the part of the pituitary that controls the not present at birth, but happens later in
thyroid—another hormone-producing life. The mutation occurs in a gene that
gland—then thyroid hormones may regulates the transmission of chemical sig­
decrease. Too little thyroid hormone can nals within pituitary cells. It permanently
cause weight gain, fatigue, and hair and switches on the signal that tells the cell to
skin changes. If the tumor affects the part divide and secrete GH. The events within
of the pituitary that controls the adrenal the cell that cause disordered pituitary cell
gland, the hormone cortisol may decrease. growth and GH oversecretion currently are
Too little cortisol can cause weight loss, the subject of intensive research.
dizziness, fatigue, low blood pressure,
and nausea. Nonpituitary Tumors
Some GH-secreting tumors may also Rarely, acromegaly is caused not by pitu­
secrete too much of other pituitary hor­ itary tumors but by tumors of the pancreas,
mones. For example, they may produce lungs, and other parts of the brain. These
prolactin, the hormone that stimulates the tumors also lead to excess GH, either
mammary glands to produce milk. Rarely, because they produce GH themselves or,
adenomas may produce thyroid-stimulating more frequently, because they produce
hormone. Doctors should assess all pitu­ GHRH, the hormone that stimulates the
itary hormones in people with acromegaly. pituitary to make GH. When these non-
pituitary tumors are surgically removed,
Rates of GH production and the aggres­ GH levels fall and the symptoms of acro­
siveness of the tumor vary greatly among megaly improve.
people with adenomas. Some adenomas
grow slowly and symptoms of GH excess In patients with GHRH-producing, non-
are often not noticed for many years. pituitary tumors, the pituitary still may be
Other adenomas grow more rapidly and enlarged and may be mistaken for a tumor.
invade surrounding brain areas or the Physicians should carefully analyze all
venous sinuses, which are located near the “pituitary tumors” removed from patients
pituitary gland. Younger patients tend to with acromegaly so they do not overlook
have more aggressive tumors. Regardless the rare possibility that a tumor elsewhere
of size, these tumors are always benign. in the body is causing the disorder.

 Acromegaly
How common is acromegaly? More accurate information is obtained
when GH is measured under conditions
Small pituitary adenomas are common,
that normally suppress GH secretion.
affecting about 17 percent of the popula­
Health care professionals often use the
tion.1 However, research suggests most of
oral glucose tolerance test to diagnose
these tumors do not cause symptoms and
acromegaly because drinking 75 to 100
rarely produce excess GH.2 Scientists esti­
grams of glucose solution lowers blood GH
mate that three to four out of every million
levels to less than 1 nanogram per milliliter
people develop acromegaly each year and
(ng/ml) in healthy people. In people with
about 60 out of every million people suf­
GH overproduction, this suppression does
fer from the disease at any time. Because
not occur. The oral glucose tolerance test
the clinical diagnosis of acromegaly is often
is a highly reliable method for confirming a
missed, these numbers probably underesti­
diagnosis of acromegaly.
mate the frequency of the disease.
Physicians also can measure IGF-I levels,
How is acromegaly diagnosed? which increase as GH levels go up, in peo­
ple with suspected acromegaly. Because
Blood Tests IGF-I levels are much more stable than GH
If acromegaly is suspected, a doctor must levels over the course of the day, they are
measure the GH level in a person’s blood often a more practical and reliable screen­
to determine if it is elevated. However, ing measure. Elevated IGF-I levels almost
a single measurement of an elevated always indicate acromegaly. However, a
blood GH level is not enough to diagnose pregnant woman’s IGF-I levels are two to
acromegaly: Because GH is secreted three times higher than normal. In addi­
by the pituitary in impulses, or spurts, tion, physicians must be aware that IGF-I
its concentration in the blood can vary levels decline with age and may also be
widely from minute to minute. At a given abnormally low in people with poorly con­
moment, a person with acromegaly may trolled diabetes or liver or kidney disease.
have a normal GH level, whereas a GH
level in a healthy person may even be Imaging
five times higher. After acromegaly has been diagnosed by
measuring GH or IGF-I levels, a magnetic
resonance imaging (MRI) scan of the
pituitary is used to locate and detect the
1
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge size of the tumor causing GH overproduc­
WE, Vance ML, McCutcheon IE. The prevalence tion. MRI is the most sensitive imaging
of pituitary adenomas: a systematic review. Cancer. technique, but computerized tomogra­
200;101():61–619.
phy (CT) scans can be used if the patient
2
Rumboldt Z. Pituitary adenomas. Topics in Mag­ should not have MRI. For example, people
netic Resonance Imaging: TMRI. 2005;16():277–288. who have pacemakers or other types of

Ayuk J, Sheppard MC. Growth hormone and implants containing metal should not have
its disorders. Postgraduate Medical Journal. an MRI scan because MRI machines con­
2006;82:2–0. tain powerful magnets.

 Acromegaly
If a head scan fails to detect a pituitary Surgery is most successful in patients with
tumor, the physician should look for non- blood GH levels below 5 ng/ml before
pituitary “ectopic” tumors in the chest, the operation and with pituitary tumors
abdomen, or pelvis as the cause of excess no larger than 10 millimeters (mm) in
GH. The presence of such tumors usually diameter. Success depends in large part
can be diagnosed by measuring GHRH on the skill and experience of the surgeon,
in the blood and by a CT scan of possible as well as the location of the tumor. Even
tumor sites. with the most experienced neurosurgeon,
the chance of a cure is small if the tumor
Rarely, a pituitary tumor secreting GH may
has extended into critical brain structures
be too tiny to detect even with a sensitive
or into the cavernous sinus where surgery
MRI scan.
could be risky.

How is acromegaly treated? The success rate also depends on what level
of GH is defined as a cure. The best mea­
Currently, treatment options include surgi­ sure of surgical success is normalization of
cal removal of the tumor, medical therapy, GH and IGF-I levels. The overall rate of
and radiation therapy of the pituitary. remission—control of the disease—after
Goals of treatment are to surgery ranges from 55 to 80 percent. (See
For More Information to locate a board-
• reduce excess hormone production to
certified neurosurgeon.)
normal levels
• relieve the pressure that the growing A possible complication of surgery is
pituitary tumor may be exerting on the damage to the surrounding normal pitu­
surrounding brain areas itary tissue, which requires lifelong use of
pituitary hormone replacement. The part
• preserve normal pituitary function or
of the pituitary that stores antidiuretic
treat hormone deficiencies
hormone—a hormone important in water
• improve the symptoms of acromegaly balance—may be temporarily or, rarely,
permanently damaged and the patient may
Surgery require medical therapy. Other potential
Surgery is the first option recommended problems include cerebrospinal fluid leaks
for most people with acromegaly, as it is and, rarely, meningitis. Cerebrospinal
often a rapid and effective treatment. The fluid bathes the brain and can leak from
surgeon reaches the pituitary via an incision the nose if the incision area doesn’t heal
through the nose or inside the upper lip well. Meningitis is a bacterial or viral infec­
and, with special tools, removes the tumor tion of the meninges, the outer covering of
tissue in a procedure called transsphenoidal the brain.
surgery. This procedure promptly relieves
the pressure on the surrounding brain Even when surgery is successful and hor­
regions and leads to a rapid lowering of GH mone levels return to normal, people with
levels. If the surgery is successful, facial acromegaly must be carefully monitored for
appearance and soft tissue swelling improve years for possible recurrence of the disease.
within a few days. More commonly, hormone levels improve,
but do not return to normal. Additional
treatment, usually medications, may be
required.

5 Acromegaly
Medical Therapy The second medication group is the GH
Medical therapy is most often used if receptor antagonists (GHRAs), which
surgery does not result in a cure and some­ interfere with the action of GH. They nor­
times to shrink large tumors before surgery. malize IGF-I levels in more than 90 percent
Three medication groups are used to treat of patients. They do not, however, lower
acromegaly. GH levels. Given once a day through injec­
tion, GHRAs are usually well-tolerated by
Somatostatin analogs (SSAs) are the first patients. The long-term effects of these
medication group used to treat acromegaly. drugs on tumor growth are still under study.
They shut off GH production and are Side effects can include headaches, fatigue,
effective in lowering GH and IGF-I levels and abnormal liver function.
in 50 to 70 percent of patients. SSAs also
reduce tumor size in around 0 to 50 per­ Dopamine agonists make up the third
cent of patients but only to a modest medication group. These drugs are not as
degree. Several studies have shown that effective as the other medications at lower­
SSAs are safe and effective for long-term ing GH or IGF-I levels, and they normalize
treatment and in treating patients with IGF-I levels in only a minority of patients.
acromegaly caused by nonpituitary tumors. Dopamine agonists are sometimes effective
Long-acting SSAs are given by intra­ in patients who have mild degrees of excess
muscular injection once a month. GH and have both acromegaly and hyper­
prolactinemia—too much of the hormone
Digestive problems––such as loose stools, prolactin. Dopamine agonists can be used
nausea, and gas––are a side effect in about in combination with SSAs. Side effects
half of people taking SSAs. However, the can include nausea, headache, and light­
effects are usually temporary and rarely headedness.
severe. About 10 to 20 percent of patients
develop gallstones, but the gallstones do
not usually cause symptoms. In rare cases,
treatment can result in elevated blood glu­ Agonist: A drug that binds to a recep­
cose levels. More commonly, SSAs reduce tor of a cell and triggers a response
the need for insulin and improve blood by the cell, mimicking the action of a
glucose control in some people with acro­ naturally occurring substance.
megaly who already have diabetes.
Antagonist: A chemical that acts within
the body to reduce the physiological
activity of another chemical substance
or hormone.

6 Acromegaly
Radiation Therapy Which treatment for
Radiation therapy is usually reserved for acromegaly is most effective?
people who have some tumor remaining
No single treatment is effective for all
after surgery and do not respond to medi­
patients. Treatment should be individual­
cations. Because radiation leads to a slow
ized, and often combined, depending on
lowering of GH and IGF-I levels, these
patient characteristics such as age and
patients often also receive medication to
tumor size.
lower hormone levels. The full effect of
this therapy may not occur for many years. If the tumor has not yet invaded surround­
ing nonpituitary tissues, removal of the
The two types of radiation delivery are con­
pituitary adenoma by an experienced
ventional and stereotactic. Conventional
neurosurgeon is usually the first choice.
radiation delivery targets the tumor with
Even if a cure is not possible, surgery may
external beams but can damage surround­
be performed if the patient has symptoms
ing tissue. The treatment delivers small
of neurological problems such as loss of
doses of radiation multiple times over
peripheral vision or cranial nerve problems.
 to 6 weeks, giving normal tissue time to
After surgery, hormone levels are mea­
heal between treatments.
sured to determine whether a cure has
Stereotactic delivery allows precise target­ been achieved. This determination can
ing of a high-dose beam of radiation at the take up to 8 weeks because IGF-I lasts a
tumor from varying angles. The patient long time in the body’s circulation. If
must wear a rigid head frame to keep the cured, a patient must be monitored for a
head still. The types of stereotactic radia­ long time for increasing GH levels.
tion delivery currently available are proton
If surgery does not normalize hormone lev­
beam, linear accelerator (LINAC), and
els or a relapse occurs, an endocrinologist
gamma knife. With stereotactic delivery,
should recommend additional drug ther­
the tumor must be at least 5 mm from the
apy. With each medication, long-term
optic chiasm to prevent radiation damage.
therapy is necessary because their with­
This treatment can sometimes be done in a
drawal can lead to rising GH levels and
single session, reducing the risk of damage
tumor re-expansion.
to surrounding tissue.
Radiation therapy is generally reserved for
All forms of radiation therapy cause a
patients whose tumors are not completely
gradual decline in production of other
removed by surgery, who are not good
pituitary hormones over time, resulting
candidates for surgery because of other
in the need for hormone replacement in
health problems, or who do not respond
most patients. Radiation also can impair
adequately to surgery and medication.
a patient’s fertility. Vision loss and brain
injury are rare complications. Rarely,
secondary tumors can develop many years
later in areas that were in the path of the
radiation beam.

7 Acromegaly
Points to Remember Hope through Research
• Acromegaly is a hormonal disorder Researchers continue to study treatment
that results from too much growth options for people with acromegaly. Stud­
hormone (GH) in the body. ies are examining the safety and effective­
ness of different types, dosages, dosing
• In most people with acromegaly, a
schedules, and combinations of somatosta­
benign tumor of the pituitary gland
tin analogs and GH receptor antagonists,
produces excess GH.
both before and after transsphenoidal
• Common features of acromegaly surgery. Another study is evaluating the
include abnormal growth of the hands effects of GH replacement in adults with a
and feet; bone growth in the face that history of acromegaly who are now growth
leads to a protruding lower jaw and hormone deficient. Other research seeks
brow and an enlarged nasal bone; joint to identify new genes that predispose peo­
aches; thick, coarse, oily skin; and ple to endocrine tumors.
enlarged lips, nose, and tongue.
• Acromegaly can cause sleep apnea, For More Information
fatigue and weakness, headaches, American Association of Neurological
impaired vision, menstrual abnormali­ Surgeons
ties in women, and erectile dysfunc­ 5550 Meadowbrook Drive
tion in men. Rolling Meadows, IL 60008
Phone: 1–888–566–AANS (2267)
• Acromegaly is diagnosed through a
or 87–78–0500
blood test. Magnetic resonance imag­
Email: [email protected]
ing (MRI) of the pituitary is then used
Internet: www.NeurosurgeryToday.org
to locate and detect the size of the
tumor causing GH overproduction. For information about pituitary conditions:
www.neurosurgerytoday.org/what/
• The first line of treatment is usually
patient_e/pituitary.asp
surgical removal of the tumor. Medi­
cation or radiation may be used
instead of or in addition to surgery.

8 Acromegaly
To locate a board-certified neurosurgeon: Clemmons DR, Chihara K, Freda PU,
www.neurosurgerytoday.org/findaneuro Ho KKY, Klibanski A, Melmed S, Shalet
SM, Strasburger CJ, Trainer PJ, Thorner
The Hormone Foundation
MO. Optimizing control of acromegaly:
801 Connecticut Avenue, Suite 900
integrating a growth hormone receptor
Chevy Chase, MD 20815–5817
anta­gonist into the treatment algorithm.
Phone: 1–800–HORMONE (67–666)
The Journal of Clinical Endocrinology &
Fax: 01–91–0259
Metabolism. 200;88:759–767.
Email: [email protected]
Internet: www.hormone.org Holdaway IM. Treatment of acromegaly.
Hormone Research. 200;62(Suppl. ):
The Pituitary Society
79–92.
VA Medical Center
2 East 2rd Street, Room 1608aW Hurley DM, Ho KKY. Pituitary disease in
New York, NY 10010 adults. The Medical Journal of Australia.
Phone: 212–26–6772 April 19, 200;180:19–25.
Fax: 212–7–6219
Levy A. Pituitary disease: presentation,
Internet: www.pituitarysociety.org
diagnosis, and management. Journal of
The following guidelines and articles about Neurology, Neurosurgery, and Psychiatry.
acromegaly can be found in medical librar­ 200;75:7–52.
ies, some college and university libraries,
Melmed S. Medical progress: acromegaly.
and through interlibrary loan in most pub­
New England Journal of Medicine. Decem­
lic libraries:
ber 1, 2006;55(2):2558–257.
American Association of Clinical Endocri­
Muller AF, van der Lely AJ. Pharmaco­
nologists Medical Guidelines for Clinical
logical therapy for acromegaly: a clinical
Practice for the Diagnosis and Treatment
review. Drugs. 200;6(16):1817–188.
of Acromegaly. Endocrine Practice.
May/June 200;10():21–225.
Ayuk J, Sheppard MC. Growth hormone
and its disorders. Postgraduate Medical
Journal. 2006;82:2–0.
Biochemical Assessment and Long-Term
Monitoring in Patients with Acromegaly:
Statement from a Joint Consensus Confer­
ence of The Growth Hormone Research
Society and The Pituitary Society. The
Journal of Clinical Endocrinology &
Metabolism. 200;89(7):099–102.

9 Acromegaly
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U.S. DEPARTMENT OF HEALTH

AND HUMAN SERVICES
National Institutes of Health

NIH Publication No. 08–3924

May 2008