Changes in Facial Features in Acromegaly
WHAT IS ACROMEGALY?
Acromegaly is a very rare disorder caused, in most cases, by a tumor of the pituitary gland that produces too much growth hormone (GH). Nearly all pituitary tumors, including those that cause acromegaly, are benign, and not malignant. However, they can become quite large and expand beyond the normal confines of the pituitary gland. Rarely, acromegaly can be caused by a tumor located in other areas of the body.
Effects on Children & Adults?
HOW DOES ACROMEGALY AFFECT CHILDREN AND ADULTS?
Acromegaly can develop in people of any age but usually affects adults between the ages of 30 and 50. If acromegaly occurs in children it causes gigantism, where the skeleton grows very quickly as an excessive amount of growth hormone is released by the pituitary tumor. Without treatment the child grows very tall.
The structure of the bones of the arms and legs changes at around 17 or 18 years, when a person stops growing. This makes them unable to grow taller in adulthood. If acromegaly develops after a person has stopped growing normally, it does not affect their height. However there are many other distinctive symptoms of acromegaly in both children and adults, and over years it can have serious health consequences such as diabetes, high blood pressure and increased risk of heart disease and colon polyps.
WHAT ARE THE SYMPTOMS OF ACROMEGALY?
The development of symptoms in acromegaly varies from patient to patient. Symptoms tend to develop gradually and the changes may not be noticed for years. Symptoms can develop due to both the increase in growth hormone levels and the physical presence of the growing tumor in the brain.
The effects of acromegaly can be very distressing and unpleasant, but most can be improved or reversed with treatment.
The abnormal growth hormone production leads to overproduction of another substance, IGF-I, which stimulates growth of bones and other tissues in the body. This can cause your hands, feet, and other parts of your body to enlarge. You may find that rings become tighter or need to be cut off and shoe size may increase. Overgrowth of tissue in the hands can cause nerves to be compressed, resulting in tingling or pains in the hands - known as carpal tunnel syndrome. Your facial features may change, perhaps making the jaw and forehead more prominent and enlarging the lips, nose and tongue. Skin may become thick and oily and excessive sweating can be a problem. Headaches are also a common symptom.
As the tumor grows it may cause headaches or impair peripheral vision as it presses on nearby nerves that run from the eyes to the brain. The tumor may damage the rest of the pituitary gland and cause underproduction of other hormones. The pituitary regulates many body processes and damage to it in this way commonly results in problems with impotence, infertility, or irregular periods.
In addition to physical symptoms, acromegaly can be emotionally very traumatic. Symptoms such as loss of libido, exhaustion and changing body image can be stressful, particularly as there may be some time before correct diagnosis and discussion of treatment. Even after this, anxiety about anticipated surgery so close to the brain and an understanding that recovery can take a while for some people can be difficult to cope with.
WHAT ARE THE SYMPTOMS OF ACROMEGALY?
With acromegaly, you have higher than normal levels of growth hormone circulating in your blood due to continual overproduction by a tumor. To diagnose the condition, physicians must test your level of growth hormone. There are two ways this is commonly done.
Growth hormone secretion by the pituitary gland into the bloodstream leads to the production and release of insulin-like growth factor-one (IGF-I) from the liver and other tissues. If GH levels are high, IGF-I levels will also be high. Because IGF-I levels are much more stable over the course of a day than GH levels, this is often a more reliable test. The IGF-I test can be done with a single blood draw at any time of day, and need not be a fasting sample. For these reasons, it has become the first test ordered to investigate excessive growth hormone secretion in many cases.
Glucose Tolerance Test
Growth hormone production fluctuates widely throughout the day but is normally suppressed after sugar-containing food or drink is eaten or drunk. For patients with acromegaly, sugar consumption will not reduce the high levels of the hormone, as it does for patients without acromegaly. The glucose tolerance test is very reliable and is usually done in initial investigations for the condition. You will take a sugary drink and the doctor will then take and test blood for sugar and growth hormone at intervals over 2 hours.
If acromegaly is confirmed from the results of the tests above, the doctor will want to check that the non-tumor part of your pituitary gland is still functioning correctly. To do this he or she tests your blood for other pituitary hormones. If some are low or missing altogether they will be replaced with specific hormones - pills or injections that may need to be taken for the rest of your life.
Next, the doctor will want to see exactly where and how big the pituitary tumor is. To do this an MRI scan is used. This type of brain scan is not painful. However, it requires the patient to lie in the tunnel-like scanner for about half an hour. A sedative can be provided if you are claustrophobic or anxious about it.
TREATMENT OF ACROMEGALY
Acromegaly is treated very successfully in most cases. The aims of treatment are to reduce GH and IGF-I production to normal levels in order to reverse or improve the symptoms, and to prevent or minimize damage to the rest of the pituitary gland and surrounding brain tissue by relieving the pressure exerted by the tumor.
Surgery to remove the pituitary tumor is often the preferred treatment, as it tends to give the best results in the shortest time. If an operation is not possible in your case, then drug treatment and/or radiotherapy may be used instead. Doctors often require a combination of treatments tailored to your needs and symptoms to get the very best results.
The pituitary is located at the base of the brain, right in the middle of the skull. To reach it, and remove a tumor, the surgeon makes a small incision at the back of the nose. This is called transsphenoidal surgery and, in most patients with acromegaly, avoids more invasive surgery. From here the pituitary gland can be seen and the surgeon uses special tools to remove the tumor tissue. The operation usually takes about an hour and, in the best cases, the results can begin to be seen soon afterwards. For example, facial features may begin to improve within a few days. Most often, the soft tissue changes are the first to noticeably improve. Sometimes, although GH levels have been reduced by the operation, the acromegaly is not cured. In these instances you may be given additional treatment such as drug therapy and/or radiotherapy.
Results depend on the size of the tumor and the skill of the surgeon. Removal of small tumors is generally more successful than large ones and it is important to make sure that your surgeon is experienced in operating on the pituitary. If the tumor is completely removed and hormone levels return to normal, then surgery may be the only treatment for acromegaly you will need.
There are three different types of drug used to treat acromegaly currently: ‘dopamine agonists’, ‘somatostatin analogs’ and ‘growth hormone receptor antagonists’. Your doctor will advise on which is best for you and this will be reviewed as treatment continues in case your condition is not improving or you are experiencing unpleasant side effects from one particular type.
Drug therapy may be chosen after surgery is determined to not completely improve your acromegaly, or in some cases, as an initial therapy without surgery.
Dopamine agonists such as bromocriptine (brand name Parlodel) and cabergoline (brand name Dostinex) inhibit GH release from the tumor. These drugs are the easiest to use as they are taken by mouth, especially cabergoline which is taken just twice weekly, whereas bromocriptine must be taken two or three times daily. However they are not always effective in treating acromegaly. Less than half of patients see a lowering of GH levels or reduction in tumor size with dopamine agonists. Additionally, side effects such constipation and dizziness when standing can be experienced. If the drug is introduced slowly and dosage built up over time these effects can usually be avoided.
Dopamine agonists are often thought of as first line medical therapy, however they are less effective than the other medications. However, dopamine agonists are easier to take and are less costly so the may be used in some cases, but other medications are more commonly used to treat acromegaly. If dopamine agonists are not working for you, your doctor may change your medication to ‘somatostatin analogs’. Dopamine agonists and somatostatin analogs have the same aim, to stop the tumor releasing growth hormone, but they act in different ways.
Two types of somatostatin analogs are available: octreotide (brand name Sandostatin) and lanreotide (brand name Somatuline). Octreotide comes in two forms, the first of which must be injected under the skin (subcutaneously) three times a day. Patients are given training to correctly inject themselves with this medication. The second form is longer-lasting (brand name Sandostatin LAR Depot) and is injected once a month deep into muscle (intramuscularly). A nurse usually performs the intramuscular injections.
Lanreotide is available as a deep subcutaneous injection (brand name Somatuline Depot) that is also long lasting. Injections are usually given once a month but can be given less frequently to some patients. The injection can be given by a nurse, and can also be given by the patient or the patient’s partner. There is little difference in the effectiveness of these two somatostatin analogs. In addition to their effects on reducing GH and IGF-I levels, somatostatin analogs decrease the size of the tumor in most patients.
Somatostatin analogs can cause side effects of the stomach or digestive system. When you start the treatment, it may cause bloating or diarrhea, although this tends to wear off after a few days. Long-term you may experience side effects such as gas or nausea, and octreotide may cause gallstones, although these rarely cause problems.
The third type of drug treatment is a growth hormone receptor antagonist, and the only drug in its class is called pegvisomant (brand name Somavert). Unlike dopamine agonists and somatostatin analogs, pegvisomant does not stop the production of GH by the tumor. Instead it stops the hormone from taking effect in the body. Pegvisomant is taken in the form of a daily injection under the skin that patients can administer themselves. The drug is well-tolerated though patients must be tested for liver abnormalities while on therapy. Also, pegvisomant does not improve headaches and does not reduce tumor size or growth.
If it is not possible for you have an operation, or if some tumor tissue remains after surgery that is not responsive to drug therapy, radiotherapy (treatment with targeted radiation) might be needed. Please rest assured, even if you are offered radiotherapy for acromegaly it does not mean that you have cancer. There are a variety of types of radiotherapy, but all work using the same principle. Depending on the type of radiotherapy, radiation beams carefully targeted at the tumor are given in small doses at a single time or daily over a month or so. Radiotherapy causes a gradual reduction in tumor size and GH release, so improvement of the acromegaly is not as quick or as noticeable as with surgery. However you may continue to see the results of radiotherapy over several years. Your doctor will monitor you for years after the radiation treatment because it is common that other pituitary functions are affected by the radiation and you may need pituitary hormone replacement therapy.
Drug treatment is usually given to reduce your GH and IGF-I levels while you wait to see results from the radiotherapy.
A doctor monitors the success of treatment for acromegaly carefully in each individual patient. This is done by assessing the problems acromegaly causes you and by measuring the relevant hormones. Your doctor will ask if there has been a change in hands, feet, or other areas, and discuss changes in other symptoms that you might have noticed. Blood tests to measure GH and IGF-I levels will be taken several times each year. The aim of treatment is to lower your GH level to less than 1 ng/ml and to have your IGF-I level in the normal range for your age.
What You Can Expect from Treatment
If surgery isn’t an option, or if it is not successful, it may take a little time for your doctor to find the best treatment suited to you. However, once an appropriate therapy is found, you can expect to start seeing a significant improvement in your symptoms. With treatment such as radiotherapy, changes will be gradual and can take months or even years to give full results, whereas benefits from surgery and drug therapy are often seen within days or weeks.
Once treatment is successful you can expect to notice that your hands and feet become less swollen and decrease in size – relieving any carpal tunnel syndrome – while facial features often return gradually towards normal. If you were suffering from excess sweating this should decrease and, if you had type 2 diabetes, it should improve or disappear altogether. Headaches usually improve and eyesight usually returns to normal. Life expectancy is decreased in patients with acromegaly but is restored to normal with successful treatment.