Acromegaly

What is the medical definition of acromegaly?

Acromegaly is a serious condition that occurs when the body produces too much of the hormones that control growth.

• The hormone most often affected is called growth hormone, or GH. It is produced by the pituitary gland, a tiny organ at the base of the brain.
• Growth hormone promotes growth of bone, cartilage, muscle, organs, and other tissues.

How is acromegaly caused?

When there is too much growth hormone in the body, these tissues grow larger than normal. This excessive growth can cause serious disease and even premature death.

The term acromegaly comes from Greek words meaning “extremities” and “enlargement.” Enlargement of the hands and feet is one of the most common signs of the disease.

What are the symptoms of an overactive pituitary gland?

• Other effects include enlargement of jaw and other facial bones; overgrowth ofbone and cartilage in the joints, causing arthritis, back pain, and curvature of the spine (kyphosis); swelling of the face, lips, and tongue; breathing problems during sleep (sleep apnea); thickening of the skin; carpal tunnel and other nerve entrapment syndromes; and enlargement of body organs such as the heart, thyroid gland (goiter), liver, and kidneys.
• Untreated, acromegaly is linked to early heart disease, high blood pressure, heart rhythm disorders, diabetes, and colonic polyps, a precursor of colon cancer.

Development of symptoms in acromegaly is often slow and gradual. It may be so gradual that symptoms go unnoticed for years or even decades.

• Many people do not notice the changes in their physical appearance. Even a primary care doctor may not recognize gradual acromegalic changes. Often, a family member or friend who sees the person after long intervals of time will point out the changes first.
• The diagnosis is usually delayed or sometimes missed altogether.
• The average time from onset of symptoms to diagnosis is 12 years.

Acromegaly is a rare disease.

• The most common age at diagnosis is 40-45 years, although it can affect any age.
• The condition affects all ethnic groups and strikes men and women equally.
• Acromegaly can occur in children. When it does, it is called gigantism (from the word for giant), because abnormal growth of the long bones of the arms and legs makes the child unusually tall.

Can acromegaly be cured?

People with acromegaly have almost twice the chance of dying prematurely as healthy people. Fortunately, treatment is available that can prevent serious complications and premature death. Before the condition can be treated, however, it must be recognized.

Hormones are chemicals that control important body functions such as metabolism, growth and development, and reproduction. Growth hormone, like a number of hormones, is produced by the pituitary gland. It is one in a series of hormones that control tissue growth.

• The hypothalamus, a part of the brain, produces growth hormone-releasing hormone (GHRH). GHRH stimulates the pituitary to produce growth hormone and release it into the bloodstream.
• The hypothalamus produces another hormone called somatostatin that stops secretion of growth hormone.
• Growth hormone in the bloodstream stimulates the liver to produce another hormone called insulin-like growth factor 1 (IGF-1).
• IGF-1, in turn, promotes growth of bone and other tissues.
• Normally, levels of GHRH, growth hormone, somatostatin, and IGF-1 are tightly controlled by each other in a natural “feedback loop.” This feedback loop regulates supply of these hormones in the body. For example, a high level of IGF-1 in the blood suppresses secretion of GHRH and growth hormone in healthy people. Disruption of this and other similar hormone feedback loops causes many different medical problems, referred to as endocrine disorders.
• Levels of growth hormone and related hormones also are affected by sleep, exercise, stress, food intake, and blood sugar levels.

Excess growth hormone and IGF-1 in the blood cause most of the physical problems in acromegaly.

• Too much IGF-1 causes the bone growth that leads to changes in physical appearance and function.
• Itcauses thickening of soft tissues such as skin, tongue, and muscles. Enlargement of the tongue can lead to breathing problems and sleep apnea. Overgrowth of muscles can entrap nerves, causing pain syndromes such as carpal tunnel syndrome.
• Excess IGF-1 causes enlargement of organs such as the heart, which can result in heart failure and rhythm disorders.
• Excess growth hormone changes the way the body processes sugar and fats. This can cause diabetes and high levels of fats such as triglycerides in the blood. This in turn can lead to atherosclerosis and heart disease.

In most cases of acromegaly, the excess growth hormone is produced by a tumor of the pituitary gland called adenoma.

• Secretion of growth hormone by a pituitary tumor is not controlled by the feedback loop. The end result is an excess of IGF-1, which causes abnormal tissue growth.
• Many adenomas are caused by a genetic defect, but we do not know what causes the defect. These tumors do not seem to run in families.
• Adenomas are benign tumors, which means that they do not spread to other parts of the body.
• They can, however, grow to considerable size and cause problems by pressing on and invading surrounding tissues.

The remaining cases of acromegaly are caused by other types of tumors that secrete growth hormone or GHRH.

• These other tumors may be in the pituitary gland or elsewhere in the body.
• Acromegaly caused by excess growth hormone and acromegaly caused by excess GHRH have the same signs and symptoms.

Some adenomas are aggressive, growing quickly. In these cases, the signs and symptoms of acromegaly tend to develop fairly quickly. Others grow more slowly, causing very gradual onset of symptoms. In these cases, symptoms might appear several years before the disease is diagnosed.

Symptoms can be divided into 2 groups: those that are effects of the tumor pressing on surrounding tissues and those caused by excess growth hormone and IGF-1 in the blood.

Symptoms due to pressure on surrounding tissues depend on the size of the tumor.

• Headaches and partial loss of vision are the most common symptoms.
• Partial loss of vision may occur in one or both eyes.
• Pituitary tumors also can damagethe pituitary gland itself, disrupting hormone production. The resulting hormone imbalances are responsible for symptoms such as impotence, low sex drive, and changes in the menstrual cycle.

Symptoms due to excess growth hormone or IGF-I vary widely.

• Increase in ring size or tightness of rings (due to hand swelling, “sausage-like” fingers)
• Increase in shoe size (due to foot swelling)
• Increased sweating
• Coarsening or thickening of facial features, especially the nose
• Increased prominence of jaw and/or forehead
• Thickened skin, especially on palms of hands or soles of feet
• Oily skin or acne
• Swelling of tongue
• Thickening or swelling of the neck (due to goiter)
• Arthritis (pain, swelling, or stiffness in any joint)
• Difficulty breathing during sleep (sleep apnea), causing poor sleep and excessive sleepiness during the day
• Pain, numbness, tingling, or weakness in hands and wrists (carpal tunnel syndrome)
• New overbite, underbite, or spreading out of teeth
• Large numbers of skin tags

Acromegaly that affects the heart or blood pressure or causes diabetes may have another set ofsymptoms. These do not occur in everyone with acromegaly.

• Irritability
• Fatigue
• Fainting
• Weakness
• Increased thirst or urination
• Shortness of breath
• Chest pain
• Palpitations or rapid heart beat
• Poor exercise tolerance

Any of thesesymptoms, if it lasts for more than a few weeks, warrants a visit to your health care provider. Serious symptoms such as shortness of breath or chest pain warrant immediate attention.

Acromegaly is not an easy diagnosis, and it is often missed by health care providers. Some of the signs and symptoms of acromegaly are very distinctive. Others are subtle and can bemisinterpreted. They are not always recognized as acromegaly because they develop so slowly. Enlargement of the hands, feet, or face is most often caused by accumulation of fluid in edematous states, but it can also be a finding of growth hormone excess from acromegaly.

If suspicious, your health care provider may ask you about your symptoms, other medical problems now and in the past, your family members’ medical problems, what medications you take, your work history, your habits and lifestyle, and many other questions. A detailed physical examination will look for signs and symptoms that clarify the diagnosis.

Lab tests

If your health care provider suspects acromegaly, he or she will order blood tests to help confirm that diagnosis.

Random measurement of growth hormone in the blood is usually not useful, as levels of the hormone fluctuate unpredictably. IGF-1 level is much more stable and predictable than growth hormone level. Thus, measurement of IGF-1 level is considered the most reliable test for acromegaly.

• IGF-1 and growth hormone levels together usually are used to confirm the diagnosis of acromegaly.
• Your health care provider may decide to measure your levels of IGF-binding protein-3 (IGFBP-3), a protein that interacts with IGF-1. Sometimes this can help confirm the diagnosis of acromegaly.

Because growth hormone secretion is inhibited by glucose (blood sugar), some health care providers measure what is called "glucose non suppressibility."

• First, your baseline growth hormone level is checked randomly at least twice.
• It is then checked again just before and several times in the hours after you drink a special high-sugar drink that causes the blood sugar level to rise.
• The high blood sugar level suppresses the growth hormone level in healthy people but not in people who have too much growth hormone.

The following tests may be ordered if your health care provider thinks they would be helpful:

• GHRH level
• Other hormones: These tests may be helpful in ruling out other disorders that are similar to acromegaly.
• Cholesterol and triglyceride levels

Imaging studies

After acromegaly has been confirmed by growth hormone and IGF-1 levels, you will probably undergo a CT scan or MRI of the head to confirm that you have an adenoma in your pituitary gland. If no pituitary tumor is detected, your health care provider will continue searching until the source of the excess growth hormone is found.

• CT scans of the abdomen and pelvis look for tumors of the pancreas, adrenal glands, or ovaries that might secrete growth hormone or GHRH.
• CT scan of the chest looks for lung cancer, which also can secrete growth hormone or GHRH.

The goals of therapy are to relieve and reverse the symptoms of acromegaly. This is done by normalizing production of growth hormone and IGF-1 and reducing the effects of the pituitary tumor on the surrounding tissues. A secondary goal is avoid damaging normal pituitary tissue.

At some time during the diagnosis or before beginning treatment, your health care provider will probably refer you to a specialist in hormonal disorders (endocrinologist).

Acromegaly is a serious medical condition with potentially fatal complications. Self-care is not recommended, except measures you can take to help you feel more comfortable. Ask your health care provider about treating bothersome or uncomfortable symptoms.

The choice of treatments in acromegaly depends on its cause. For the large majority of cases caused by pituitary adenomas, treatments include surgery, drug therapy, and radiation therapy.

• Often a combination of these therapies is needed to put the disease in remission. ("Remission" here means to return levels of growth hormone and IGF-1 to normal.) No one combination of therapies works best for everyone. Surgery is usually the first approach.
• If surgery alone fails to achieve complete remission, drug therapy is given.
• The success of any treatment regimen is measured by checking levels of growth hormone and IGF-1 in the bloodstream.
• IGF-1 or growth hormone measurements, or both, are repeated at intervals to monitor how well your therapy is working.

Radiation therapy usually is reserved for adenomas that are not cured by surgery and drug therapy. Radiation also is used for people who cannot undergo surgery because of other medical problems.

• Radiation treatments are given in 2 forms, external beam and stereotactic.
• External beam treatments are easier but take much longer to work, an average of 7 years.
• Stereotactic radiotherapy takes about 18 months to normalize growth hormone and IGF-1 levels.
• Many people who receive radiation therapy also receive drug therapy.
• A majority of people who undergo radiation therapy have a normal or nearly normal growth hormone level 10 years after treatment.
• Some people who undergo radiation therapy have permanent loss of pituitary function. These people must take hormone replacement for the rest of their lives.
• Some studies have linked radiation therapy with growth of other tumors.

One goal of drug therapy in acromegaly isto normalize levels of growth hormone and IGF-1 in the bloodstream.Another is to shrink the tumor.

Growth hormone receptor blockers are the newest category of drugs used for acromegaly. These drugs work by blocking the site on the cell where growth hormone "docks." If the growth hormone can't dock, it can't cause abnormal growth.

• The only drug in this category that has been approved by the US Food and Drug Administration (FDA) for acromegaly is pegvisomant (Somavert).
• In early studies, this drug normalized IGF-1 level in more than 90% of people treated.
• Pegvisomant is given by injection.
• Side effects include reaction at the injection site, sweating, headache, and fatigue.

Somatostatin analogues act like the hormone somatostatin. They work by stopping secretion of growth hormone, just as somatostatin does.

• The most widely used drug in this group by far is octreotide (Sandostatin). This drug works in most people who take it.
• Octreotide can be taken only as shots once monthly.
• It causes gastrointestinal side effects such as nausea, bloating, and gas in about 30% of people who take it.

Dopamine agonists promote the activity of dopamine, a chemical in the brain. These drugs work by stopping secretion of growth hormone by some pituitary tumors.

• The most widely used of these drugs is bromocriptine (Parlodel). It is popular because it comes in a convenient oral form and is much less expensive than octreotide.
• These drugs work in fewer than half of people who take them.
• Side effects of these drugs include gastrointestinal upsets, lightheadedness when standing up, and sinus congestion.

Surgery is the first treatment used for most people with excess growth hormone, regardless of the cause. Surgery brings about remission in some people, but not in all. People who are in remission after surgery usually need no further treatment.

• The operation of choice for pituitary adenoma is transsphenoidal hypophysectomy.The tumor is removed via one of the nasal sinuses through an incision inside the nose.
• If it is successful, this operation has 2 advantages. It rapidly improves symptoms caused by the tumor pressing on adjacent tissue, and it normalizes levels of growth hormone and IGF-I.
• While this operation technically is not brain surgery, it requires a great deal of care to avoid injuring delicate tissues surrounding the pituitary. Success depends largely on the skill and experience of the surgeon.
• Remission rates are about 80-85% for small adenomas (microadenomas) and 50-65% for large adenomas (macroadenomas).
• The growth hormone and IGF-1 levels after surgery usually indicate whether further treatment is needed.
• Some people require lifelong hormone replacement after pituitary surgery.

Acromegaly is a lifelong disease. Drug or radiation therapy typically goes on for several years. Even after successful therapy, you will need to see your health care provider regularly to have your levels of growth hormone and IGF-1checked.

There is no known way to prevent acromegaly. Early detection is the best hope of preventing severe symptoms and complications.

Treatments for acromegaly are successful in a significant number of people. Unfortunately, however, the disease is rarely caught early enough to prevent permanent damage or even premature death.

• Bone changes of acromegaly are permanent.
• Many of the soft-tissue changes, such as swelling, enlarged tongue, thickened skin, acne, and carpal tunnel syndrome are reversible with treatment. Depression and sexual problems also may improve with treatment. Goiter and other organ enlargement improve in some cases.
• Complications such as high blood pressure, diabetes, and high triglycerides start to reverse when the levels of growth hormone and IGF-1 are normalized. If these changes are reversed, serious illness, such as heart disease and stroke or death can be prevented.

Living with acromegaly presents many new challenges, both for you and for your family and friends.

• You will probably have many worries about how the disease will affect you and your ability to "live a normal life." Will you be able to care for your family and home, hold your job, and continue the friendships and activities you enjoy?
• Many people feel anxious or depressed. Some people feel angry and resentful; others feel helpless and defeated.

For most people with a serious disease, talking about their feelings and concerns helps.

• Your friends and family members can be very supportive. They may be hesitant to offer support until they see how you are coping. Don't wait for them to bring it up. If you want to talk about your concerns, let them know.
• Some people don't want to "burden" their loved ones, or prefer talking about their concerns with a more neutral professional. A social worker, counselor, or member of the clergy can be helpful if you want to discuss your feelings and concerns about having this condition. Your primary care provider or endocrinologist should be able to recommend someone.
• Many people with acromegaly are helped profoundly by talking to other people who have the disease. Sharing your concerns with others who have been through the same thing can be remarkably reassuring. This is why support groups exist. Because the disease is so rare, finding a support group in your area may be difficult, unless you live near a large medical center with many medical specialists. There are groups on the Internet that can help you find the support you need. If you do not have access to the Internet, go to your public library.

For more information about support groups, contact these agencies:

• Pituitary Network Association - (805) 499-9973
• The Hormone Foundation - (800) 467-6663