What are the symptoms?
Acromegaly is a hormonal disorder that results when a pituitary adenoma produces excess growth hormone (GH). It most commonly affects middle-aged adults and can result in serious illness and premature death.
Overgrowth of bone and cartilage often leads to arthritis. When tissue thickens, it may trap nerves, causing carpal tunnel syndrome, characterized by numbness and weakness of the hands. Other symptoms of acromegaly include thick, coarse, oily skin; skin tags; enlarged lips, nose and tongue; deepening of the voice due to enlarged sinuses and vocal cords; snoring due to upper airway obstruction; excessive sweating and skin odor; fatigue and weakness; headaches; impaired vision; abnormalities of the menstrual cycle and sometimes breast discharge in women; and impotence in men. There may be enlargement of body organs, including the liver, spleen, kidneys and heart.
What are the causes?
Acromegaly is caused by prolonged overproduction of GH by a pituitary adenoma, a benign tumor of the pituitary gland. The pituitary is a small gland at the base of the brain that produces several important hormones which control body functions including 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. 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 a pituitary tumor 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 diabetes.
In almost all 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
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. There are rare genetic syndromes in which the predisposition to acromegaly is inherited. There are also extraordinarily rare tumors occurring elsewhere in the body which can also lead to acromegaly.
The most serious health consequences of acromegaly are diabetes mellitus, hypertension, and increased risk of cardiovascular disease. Patients with acromegaly are also at increased risk for polyps of the colon that can develop into cancer. Other serious complications can include arthritis and sleep apnea. Patients with untreated acromegaly have an increased mortality rate of about 2-3 times that of the general population. With successful treatment, many of these complications improve or resolve, and life expectancy normalizes.
Preparing for your appointment
Write down questions to ask your doctor.
You're likely to start by seeing your family doctor or a general practitioner. However, in some cases when you call to set up an appointment, you may be referred immediately to an endocrinologist, a doctor who specializes in endocrine (hormonal) disorders.
Special Instructions (If available, please bring):
- Copies of your medical records/discharge summary/physician notes.
- A copy of your MRI or CT on a CD.
- A copy of your lab reports.
- Bring any medications you are taking with you to your appointment.
- Please make sure your MGH registration is accurate and up-to-date.
Our clinic assistants will help you update your hospital registration and insurance information.
How is Acromegaly Diagnosed?
If a doctor suspects acromegaly,
he or she may measure the GH level in the blood after a
patient has fasted overnight to determine if it is elevated.
However, a single measurement of an elevated blood GH level
is not enough to diagnose acromegaly, because GH is secreted
by the pituitary in pulses, and its concentration in the
blood can vary widely from minute to minute. At a given
moment, a patient with acromegaly may have a normal GH level,
whereas a GH level in a healthy person may be high.
Because of these challenges, more accurate information can
be obtained when GH is measured under conditions in which
GH secretion is normally supressed. Physicians often use
the oral glucose tolerance test to diagnose acromegaly,
because ingestion of sugar should lower blood
GH levels in healthy people. In patients
with acromegaly, this reduction does not occur. The
glucose tolerance test is a reliable method of confirming a diagnosis of acromegaly.
Another excellent way to determine whether a patient has acromegaly is to measure an IGF-1 level. Elevated GH
levels increase IGF-1 blood levels. Because IGF-1 levels
are much more stable over the course of the day, they are
often a more practical and reliable measure than GH levels.
Elevated IGF-1 levels almost always indicate acromegaly, with some exceptions such as pregnancy.
After acromegaly has been diagnosed, magnetic resonance imaging (MRI) scans of the pituitary are used to locate the pituitary adenoma that causes the GH overproduction.
How is Acromegaly treated?
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 or restore 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 pituitary tumor.
No single treatment is effective for all patients. Treatment should be individualized depending on patient characteristics, such as age and tumor size. Removal of the pituitary adenoma by an experienced neurosurgeon is usually first-line therapy. If surgery does not normalize hormone levels or a relapse occurs, treatment with medicaions is usually an option. Medications that are used to treat acromegaly include cabergoline (a dopamine agonist), octreotide and lanreotide (somatostatin agonists) and pegvisomant (a GH receptor antagonist). Although these medications help to control the disease, none of these medications are curative, and long-term therapy is necessary. In some patients who are not surgical candidates, medication can be used as first-line treatment. Radiation therapy is generally for patients who do not respond adequately to surgery and medication.
- SURGERY -- Surgery is a rapid and effective treatment. The surgeon
reaches the pituitary through an incision in the nose and,
with special tools, removes the tumor tissue in a procedure
called transsphenoidal surgery. This procedure promptly
relieves the pressure on the surrounding brain regions and
leads to a lowering of GH levels. If the surgery is successful,
soft tissue swelling improves within
a few days. Success depends on the skill and experience of the surgeon and size and locatin onf the tumor.
of surgery are rare but may include cerebrospinal fluid leaks, meningitis,
or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement.
Even when surgery is successful and hormone levels return to normal, patients must be carefully monitored for years for possible recurrence. If surgery is not successful at completely normalizing IGF-1 levels, additional treatment is required.
- DRUG THERAPY-- There are a number of medications that are effective treatments in acromegaly. These include:
- RADIATION THERAPY -- Radiation therapy has been used both as a primary treatment and combined with surgery or drugs. It is usually reserved for patients who have tumor remaining after surgery who do not respond to medication or who do not wish to take medications lifelong. Radiation therapy does not immediately lower GH or IGF-1 levels, and adjuncctive medical therapy is required until hormone levels normalize. Radiation therapy can be given as one dose ("stereotactic radiosurgery") or in multiple small doses over 4-6 weeks ("fractionated treatment"). At the MGH, a special form of stereotactic radiation, known as "proton beam" treatment, is used. Proton beam therapy minimizes the damage to surrounding tissue, including brain and optic nerves. This treatment normalizes GH and IGF-1 levels in about 50% of patients over 4-5 years. Radiation therapy can cause a gradual loss of production of other pituitary hormones over time, and therefore levels need to be monitored annually by an endocrinologist in all patients who receive radiation. Loss of vision, brain injury, and secondary neoplasms, which have been reported, are very rare complications of radiation treatments.
What research is being done on Acromegaly?
The Neuroendocrine Clinical and Pituitary Center is committed to advance the treatment of patients with acromegaly through research. Current research projects are described in the Neuroendocrine Clinical and Pituitary Center Bulletin below. We welcome patient participation in the research.