The main treatment of many pituitary tumors is surgery. How well the surgery works depends on the type of tumor, its exact location, its size, and whether it has spread into nearby tissues.
Transsphenoidal surgery: This is the most common way to remove pituitary tumors. Transsphenoidal means that the surgery is done through the sphenoid sinus, a hollow space in the skull behind the nasal passages and below the brain. The back wall of the sinus covers the pituitary gland.
For this approach, the neurosurgeon makes a small incision along the nasal septum (the cartilage between the 2 sides of the nose) or under the upper lip (above the upper teeth). To reach the pituitary, the surgeon opens the boney walls of the sphenoid sinus with small surgical chisels, drills, or other instruments depending on the thickness of the bone and sinus.
A newer approach is to use an endoscope, a thin fiber-optic tube with a tiny camera lens at the tip. In this approach, the incision under the upper lip or the front part of the nasal septum is not needed, because the endoscope allows the surgeon to see well through a small incision that is made in the back of the nasal septum. The surgeon passes instruments through normal nasal passages and opens the sphenoid sinus to reach the pituitary gland and remove the tumor. The use of this technique is limited by the tumor’s position and the shape of the sphenoid sinus.
The transsphenoidal approach has many advantages. First, no part of the brain is touched during the approach, so the chance of damage to the brain is very low. There is also no visible scar. But it is hard to remove large tumors this way. When the surgery is done by an experienced neurosurgeon and the tumor is a microadenoma, the cure rates are high (greater than 80%). If the tumor is large or has grown into the nearby structures (such as nerves, brain tissue, or the tissues covering the brain) the chances for a cure are lower and the chances of brain, nerve, and blood vessel injury are greater.
Craniotomy: Less commonly, for larger or more complicated pituitary tumors, a craniotomy may be needed. In this approach the surgeon operates through an opening in the front and side of the skull. The surgeon has to carefully work beneath and between the lobes of the brain to reach the tumor. Although the craniotomy has a higher chance of brain injury than transsphenoidal surgery for small lesions, it is actually safer for large and complex lesions because it provides better visualization and control of important nerves and blood vessels.
For both transsphenoidal surgery and craniotomies, the doctor may use image-guidance with MRI or CT scans before surgery to help plan the best surgical approach. Some centers now use intraoperative MRI (where MRI scans are done in the operating room one or more times during the surgery) in some cases, but many doctors still consider this to be experimental.
As a general rule for pituitary tumors, the larger and more invasive the tumor, the less likely the tumor can be cured by surgery. Smaller tumors are more easily treated with surgery.
Possible side effects of surgery
Surgery on the pituitary gland is a serious operation, and surgeons are very careful to try to limit any problems either during or after surgery. Complications during or after surgery such as bleeding, infections, or reactions to anesthesia are rare, but they can happen. Most people who have transsphenoidal surgery will have a sinus headache and congestion for up to a week or 2 after surgery.
Damage to large arteries, to nearby brain tissue, or to nerves near the pituitary rarely can result in brain damage, a stroke, or blindness. When doctors operate on the pituitary gland, they must create a temporary pathway between the nasal sinuses and airways and the brain. Until this heals, meningitis (infection and inflammation of the meninges) can result. Damage to the meninges can also lead to leakage of cerebrospinal fluid (the fluid that bathes and cushions the brain).
Diabetes insipidus may occur right after surgery, but it usually gets better with time. This condition usually improves on its own within 1 to 2 weeks after surgery. If it is permanent, it can be treated with a desmopressin nasal spray.
Damage to the rest of the pituitary can lead to other symptoms from a lack of pituitary hormones. This is rare after surgery for small tumors, but may be unavoidable when treating some larger macroadenomas. If levels of pituitary hormones are low after surgery, this can be treated with medicine to replace certain hormones normally made by the pituitary and other glands.
Radiation therapy for pituitary tumors
Radiation therapy uses high energy x-rays or particles to kill tumor cells. This type of treatment is given by a doctor called a radiation oncologist. Radiation is directed at the tumor from a source outside the body.
Radiation therapy may be recommended if surgery is not an option, if a pituitary tumor remains or comes back after surgery, or if it causes symptoms that are not relieved by medicines.
Treatment may be given with conventional radiation therapy or with newer techniques.
Radiation therapy is much like getting an x-ray, although the doses of radiation used are much higher. Before your treatments start, the radiation team will get imaging tests such as MRI scans to define the exact size and shape of the tumor. This is used to determine the correct angles for aiming the radiation beams, the shape of the beams, and the proper dose of radiation.
Conventional radiation is often given in a series of treatments, usually 5 times a week over 4 to 6 weeks. At each session, you lie on a special table while a machine delivers the radiation from precise angles. The treatment is not painful. Each session lasts about 15 to 30 minutes. Much of that time is spent making sure the radiation is aimed correctly. The actual treatment time each day is much shorter.
This therapy can be very effective, but it also has some drawbacks:
It works slowly, so it can take months or years before the tumor growth and/or hormone production is fully controlled.
It can damage the remaining normal pituitary. In most cases, normal pituitary function will be lost over time, requiring treatment with hormones.
It may damage some normal brain tissue, particularly near the pituitary gland, which could affect mental function years later.
The optic nerves may be damaged, resulting in impaired vision.
The radiation may increase the risk of developing a brain tumor later in life, although this risk is still likely to be low.
These risks are likely to be lower with the use of newer techniques that focus the radiation more precisely on the pituitary, such as intensity modulated radiation therapy (IMRT), stereotactic radiation, and proton beam therapy. The use of these techniques may be limited for some tumors that are very close to the optic nerves.
Intensity modulated radiation therapy (IMRT)
IMRT is an advanced form of three-dimensional radiation therapy. It uses a computer-driven machine that actually moves around the patient as it delivers the radiation. IMRT lets the doctor shape the radiation beams and aim them at the tumor from several angles. The intensity (strength) of the beams can also be adjusted to limit the dose reaching the most sensitive nearby normal tissues. This may result in fewer side effects. Many major hospitals and cancer centers now use IMRT.
Stereotactic radiosurgery/stereotactic radiation therapy
This type of treatment delivers a large, precise radiation dose to the tumor area in a single session (radiosurgery) or in a few sessions (radiotherapy). It targets the tumor more precisely, causing less harm to the remaining normal pituitary gland, and greatly limits the radiation exposure to the rest of the brain.
For this treatment, a head frame is attached to the skull to help aim the radiation beams very precisely. Once the exact location of the tumor is known from CT or MRI scans, radiation may be delivered in one of two ways.
In one approach, thin radiation beams from a machine are focused at the tumor from hundreds of different angles for a short period of time. An example of such a machine is the Gamma Knife.
Another approach uses a movable linear accelerator (a machine that creates radiation) that is controlled by a computer. Instead of delivering many beams at once, this machine moves around the head to deliver radiation to the tumor from different angles. Several machines do stereotactic radiosurgery in this way, with names such as X-Knife, CyberKnife, and Clinac.
Stereotactic radiosurgery typically delivers the whole radiation dose in a single session, though it may be repeated if needed. (There is no actual surgery involved in this treatment.) Sometimes doctors give the radiation in several treatments to deliver the same or a slightly higher dose. This is called fractionated radiosurgery or stereotactic radiotherapy.
The benefit of stereotactic radiation is usually seen a bit sooner than with other forms of radiation therapy, although it may still take months to be fully effective.
Unfortunately, this therapy cannot be used for tumors that are very close to important nerves near the pituitary, such as those needed for vision. It also might not be helpful for tumors that have an unusual shape.
Proton beam radiation therapy
This form of treatment uses a beam of protons rather than x-rays to kill cancer cells. Protons are positive parts of atoms. X-rays release their energy both before and after they hit their target, which can damage nearby healthy tissues. Protons, on the other hand, cause little damage to tissues they pass through and only release their energy after traveling a certain distance. Doctors can use this property to deliver more radiation to the tumor with less damage to nearby normal tissues. Like stereotactic radiation, it has the advantage of focusing the radiation more precisely on the pituitary tumor.
But proton beam radiation therapy requires highly specialized equipment and is not widely available – there are only a handful of proton beam centers in the United States at this time. It is not a standard treatment for pituitary tumors. Studies are still needed to see if it is safer or more effective than stereotactic radiosurgery.
Medicines to treat pituitary tumors
Several medicines can be used to treat pituitary tumors that are making hormones.
Drugs for prolactin-secreting tumors (prolactinomas)
Drugs called dopamine agonists, such as bromocriptine (Parlodel®) and cabergoline, are very effective in both blocking prolactin production by prolactinomas and preventing growth of these tumors. Although both drugs are effective, cabergoline lasts longer than bromocriptine, so it does not need to be taken as often.
Most people with prolactinomas are able to control their prolactin levels with medicine. The drugs are also very effective in reducing the size of most prolactin-secreting macroadenomas. In fact, these drugs work so well that surgery is usually not needed for prolactinomas. Only about 1 out of 5 of these tumors does not shrink with treatment. Even if the tumor doesn’t shrink, these drugs often can keep prolactinomas from growing larger. If successful, the drug treatment may be continued for life.
Possible side effects of these drugs include drowsiness, dizziness, nausea, vomiting, diarrhea or constipation, confusion, and depression. Another “side effect” is that these drugs may restore fertility in women whose high prolactin levels had been causing infertility. Cabergoline may cause fewer side effects than bromocriptine, but it might also increase the risk of heart valve problems. However, this is rare in patients taking this drug for prolactinomas.
Drugs for growth hormone-secreting tumors
Octreotide (Sandostatin®) is a man-made form of the natural hormone somatostatin. Somatostatin, which is made in the pituitary and other glands, blocks growth hormone (somatotropin) production by adenomas and returns insulin-like growth factor-1 (IGF-1) to normal levels in about two thirds of patients. It is first given as an injection under the skin 3 times per day. A longer acting form is available, which can be given as a monthly injection. A newer, similar drug called lanreotide (Somatuline®) is given as an injection about once a month. Doctors measure how well these drugs are working by testing blood growth hormone and IGF-1 levels. Tumors tend to shrink very slowly with these drugs.
Both drugs can have minor side effects, such as nausea, vomiting, diarrhea, stomach pain, dizziness, headache, and pain at the site of injection. Many of these side effects improve or even go away with time. They can also cause gallstones and may worsen diabetes if a person has it.
Dopamine agonists such as bromocriptine or cabergoline may reduce growth hormone levels in about 1 out of 5 patients. Unfortunately, higher doses are needed for these tumors than for prolactinomas, and some patients have trouble with the side effects they can cause (discussed above). An advantage of these drugs is that they can be taken as a pill.
Pegvisomant (Somavert®) is a newer drug that works by blocking the action of growth hormone on other cells. It is very effective in lowering blood IGF-1 levels, but it doesn’t block growth hormone secretion by the pituitary gland or shrink pituitary tumors. It has few side effects, although it may lower blood sugar levels and cause mild liver damage in some people. It is given by daily injection under the skin.
Drugs for corticotropin (ACTH)-secreting tumors
Medicines are not usually part of the treatment of these tumors unless surgery and radiation therapy don’t work (or if the effects of radiation have not yet been felt). Cyproheptadine (Periactin®) suppresses ACTH production in about half of these tumors. For patients who do not respond to cyproheptadine, several drugs can be used to keep the adrenal gland from making cortisol. These include ketoconazole, aminoglutethimide, etomidate, metyrapone, mifepristone, and mitotane. These drugs can be hard to take because of side effects, but they can have a clear benefit when surgery is not an option.
Drugs to treat thyrotropin (TSH)-secreting tumors
For these tumors, drugs such as octreotide and lanreotide (somatostatin analogs) can usually reduce the amount of TSH that is produced. Bromocriptine or cabergoline (dopamine agonists) can also be used. These drugs are discussed in more detail above.
Treatment of functional (hormone-producing) pituitary tumors
The treatment of functional pituitary tumors depends on which type of hormone they make.
Treatment of prolactin-secreting adenomas (prolactinomas)
Unlike most other pituitary tumors, surgery is usually not the first treatment for these tumors. Instead, medicines that block the production of prolactin (bromocriptine or cabergoline) are used . They work so well that surgery is usually not needed. Although both of these drugs are effective, cabergoline may have fewer side effects. It also lasts longer, so it does not need to be taken as often as bromocriptine.
Most patients are able to control their prolactin levels with medicine. The drugs are also very effective in reducing the size of prolactin-secreting macroadenomas. Only about 1 out of 5 of these tumors does not shrink after treatment. Even when the tumors don’t shrink, these drugs usually keep them from growing larger.
Within 3 months of starting treatment, the blood prolactin level is measured again and an MRI scan of the pituitary is done to check whether the medicine is working. If so, the drug treatment may be continued for the rest of the patient’s life. In some people, if treatment with these medicines has been successful and MRI scans show a prolonged period with no tumor remaining, the treatment may be stopped. These people will need to have regular MRIs to see if the tumor comes back. On the other hand, if after 6 months of treatment the response has not been good, or if serious side effects occur, then surgery is considered.
Some doctors recommend surgery in special situations such as in men whose tumors are at an advanced stage, or in women who want to become pregnant (the drugs must be stopped during pregnancy, and pregnancy may cause the tumor to grow fast). Surgery may also be used to treat very large tumors after first shrinking them with drug treatment.
Radiation may be used if drug treatment and surgery are not successful.
Treatment of growth hormone-secreting adenomas
Adults with these tumors often have acromegaly, while children have gigantism.
Surgery is usually the first treatment for these adenomas, although often it can’t remove all of the tumor. If growth hormone and IGF-1 levels remain high after surgery, medicines or radiation therapy may be tried. Many experts recommend treating with medicine first if the surgery doesn’t work. Radiation is used most often when drug treatment doesn’t work. This is because radiation is very slow to act and over time it can lead to lowered levels of other pituitary hormones.
Octreotide (Sandostatin®) and lanreotide (Somatuline®) are man-made forms of the natural hormone somatostatin that return insulin-like growth factor-1 (IGF-1) to normal levels in about two thirds of patients. They are taken as injections, usually about once a month. The dose of either of these drugs may need to be adjusted based on blood IGF-1 levels.
Because these drugs work well and only need to be given monthly, doctors have started to question whether surgery should always be the first treatment for people with growth hormone-secreting adenomas. In those who might have problems with surgery, such as frail elderly people, drug treatment might be a good choice as the first treatment.
Sometimes, drug treatment may be given for a short time before surgery. This may cause the tumor to shrink, which could improve the chance that the surgery will be successful, but doctors cannot be certain before trying that this will help.
Another drug, pegvisomant, works by blocking the action of growth hormone. It may be used if octreotide (or lanreotide) isn’t doing enough to block growth hormone production.
Drugs such as bromocriptine or cabergoline may be helpful in reducing growth hormone levels in about 1 out of 5 patients. Unfortunately, some patients have trouble tolerating the high doses often needed for these drugs to be effective. The main advantage of these drugs is that they are in pill form.
If surgery and drug treatments don’t work, then radiation therapy may be used.
Treatment of corticotropin (ACTH)-secreting adenomas
These tumors cause Cushing’s disease. Surgery is usually the main treatment. If the surgery doesn’t work completely or if the tumor grows back, the 2 main options are a second surgery or radiation therapy. Radiation can often take months or years to work, so medicines may be given to help control cortisol levels in the meantime.
If surgery and radiation do not control cortisol production, treatment options may include removing both of the adrenal glands (see below) or using medicines to try to control cortisol levels.
Cyproheptadine lowers ACTH production in about half of these tumors. If the ACTH level is still high while the patient is taking cyproheptadine, other drugs can be used to stop the adrenal glands from making too much cortisol. These include ketoconazole, aminoglutethimide, etomidate, metyrapone, mifepristone, and mitotane. These drugs are often hard to take for long periods because of side effects.
If medicines cannot control the cortisol level, or if the patient can’t take the drugs because of side effects, both adrenal glands can be removed with an operation called a bilateral adrenalectomy. This can usually be done with laparoscopic surgery, which uses several small incisions in the abdomen instead of one large one. The surgeon works through these small incisions with special long, thin instruments, including one with a tiny video camera lens on the end (called a laparoscope) for looking into the abdomen. Adrenalectomy stops all cortisol production, so high cortisol levels will no longer be a problem. But after the surgery the patient will need to take pills to replace the adrenal steroid hormones for the rest of their life.
Before a patient has their adrenal glands removed, the pituitary gland needs to be treated with radiation. If this is not done, removing the adrenals can cause the pituitary tumor to grow larger and even start growing into the structures near the pituitary. This is known as Nelson syndrome. When the adenoma gets large, it can damage the function of the normal parts of the pituitary gland, causing problems from hormone deficiency. It can also lead to high levels of ACTH. Because ACTH is similar to the hormone that causes tanning of the skin, the high ACTH levels make the skin darker.
Treatment of thyrotropin (TSH)-secreting adenomas
The treatment of choice for these tumors is usually surgery, sometimes along with radiation therapy. Radiation is not always helpful, and medicines may be needed to control the tumor’s hormone production. Some of the drugs that can be helpful include octreotide, lanreotide, bromocriptine, and cabergoline. These should be used only after other treatments have failed to control the tumor.
It is important to treat the pituitary tumor to prevent it from damaging nearby structures. Drugs that stop the thyroid gland from making thyroid hormone can actually make things worse because reducing thyroid hormone production may cause the TSH-secreting pituitary tumor to grow.
Treatment of gonadotropin (FSH/LH)-secreting adenomas
The hormones produced by these tumors rarely cause major symptoms, so these tumors are often not found until they are large (macroadenomas) and threaten vital structures.
Treatment of these tumors is often similar to that used for non-functional adenomas. Surgery is often the best option because it works right away. Radiation may be given after surgery.
Follow up with frequent MRI scans will tell if the tumor is growing back. If it does, options include radiation (if it hasn’t been given already) or medicines such as dopamine agonists (bromocriptine, cabergoline) or somatostatin analogs (octreotide, lanreotide).
Treatment of non-functional (not hormone-producing) pituitary tumors
Large tumors (macroadenomas) that are causing symptoms are often treated with surgery. This helps get rid of the symptoms and danger to vital structures quickly. As with gonadotropin-secreting tumors, frequent MRI scans should be done early after treatment. If there is re-growth of the adenoma, radiation therapy may be used. Drug treatment is usually not helpful in treating these tumors, but doctors have reported some success using the chemotherapy drug temozolomide for fast-growing tumors.
These small pituitary tumors (microadenomas) usually cause no symptoms and do not secrete high levels of any hormone. They are usually found during an MRI scan done for some other reason. Most doctors recommend just watching these, with regular physical exams and repeat MRI scans to see if they are growing. Hormone levels may be checked at least once as well. The important point is that people with incidentalomas should not receive unnecessary tests or treatments.
Treatment of pituitary carcinomas
Pituitary carcinomas are rare tumors that have already spread to other parts of the body when they are found. Surgery and radiation therapy are the main forms of treatment and may slow tumor growth and prevent or relieve symptoms. But in general, these tumors are very hard to treat effectively. Chemotherapy and newer targeted therapy drugs may be tried, but it’s not clear if these treatments can improve survival. Because pituitary carcinoma affects so few patients, it is hard to study which treatments might be effective. Taking part in a clinical trial of a new treatment may be a good option.
What happens after treatment for pituitary tumors?
For most people with pituitary tumors, treatment may remove or destroy the tumor. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about tumor growing or coming back. (When a tumor comes back after treatment, it is called recurrence.) This is a very common concern in people who have had a pituitary tumor.
It may take a while before your fears lessen. But it may help to know that many tumor survivors have learned to live with this uncertainty and are living full lives.
For others, the tumor may never go away completely. Some people may continue to get treatment with medicines or other treatments to help keep the tumor in check. Learning to live with a tumor that does not go away can be difficult and very stressful. It has its own type of uncertainty.
Follow-up care is very important after treatment for pituitary tumors. Even if you have completed treatment, your doctors will still want to watch you closely. Keep all of your appointments with your health care team and follow their instructions carefully. Report any new or recurring symptoms to your doctor right away. Ask questions if you don’t understand what your doctor says.
Surgery is often the first treatment for many types of pituitary adenomas. If you had a functional pituitary adenoma, hormone measurements can often be done within days or weeks after surgery to see if the treatment was successful. Blood tests will also be done to see how well the remaining normal pituitary tissue is functioning. If the results show that the adenoma was completely removed and that pituitary function is normal, you will still need periodic visits with your doctor. Your hormone levels may need to be checked again in the future to check for recurrence of the adenoma. Regardless of whether or not the tumor made hormones, MRI scans may be done as a part of follow-up. Depending on the size of the tumor and the extent of surgery, you may also be seen by a neurologist to check your brain and nerve function and an ophthalmologist (eye doctor) to assess your vision.
After radiation treatment, you will need checkups for several years. The response to radiation therapy is hard to predict, and although the benefits and side effects of treatment can occur within months, some may take years to appear. Your pituitary function will be checked at regular intervals. MRI scans will be the main follow-up tests, along with testing hormone levels if your tumor made hormones.
It is common for patients to develop pituitary hormone deficiency after surgery or radiation therapy. These people will need hormone replacement. Thyroid hormone and adrenal steroids are supplied by oral medicines. In men, testosterone can be given to restore sex drive and help prevent osteoporosis (weak bones). Testosterone is available as a gel or patch applied to the skin. It can also be given as a monthly injection. In young women, estrogen is given either by pills or a skin patch to avoid early menopause. Often, progesterone is given along with estrogen. Pituitary hormone deficiency may affect a woman’s ability to have children. However, if she wishes to become pregnant, it may be possible to restore fertility with hormone therapy.
If you are taking medicine for a prolactinoma, you will have your hormone levels checked at least once or twice a year. If an MRI shows that the tumor has shrunk after treatment, the MRI may not have to be repeated, depending on the size of the tumor and whether the response is partial or complete. If you have a prolactin-producing microadenoma, you may be able to stop drug treatment after several years of therapy. Your doctor may recommend stopping the drug and then checking your prolactin level. If it remains normal, you may be able to stay off the drug.
For patients receiving drug therapy for corticotropin (ACTH)-producing or growth hormone-producing adenomas, follow-up may be more frequent. Your hormone levels and symptoms will be monitored carefully. People with growth hormone-producing adenomas have an increased risk of developing high blood pressure and heart failure. They also have a higher risk of getting colon cancer. Periodic checkups for these conditions are recommended.
Diabetes insipidus (excessive urination) may be a short-term result of treatment, although in some cases it may lost longer. It can usually be treated effectively. If the problem is mild, simply taking in enough fluids may treat this problem. For more severe problems, desmopressin is given either by nasal spray or by tablet. It is always important to drink enough fluids to avoid dehydration.
It is also important to consider whether your pituitary tumor might be a clue to a genetic syndrome in your family. In the near future, people with pituitary tumors might be able to have genetic tests done on a sample of the tumor and blood tests to look for certain gene changes. If a change is found, family members might want to be tested as well to see if they are at increased risk.
Occasionally, people with large or fast-growing pituitary adenomas may be disabled or have their lives shortened because the tumor or its treatment destroys vital brain tissue near the pituitary gland, but this is rare. In general, when a pituitary tumor is not cured, people live out their lives but may have to deal with problems caused by the tumor or its treatment, such as hormone levels that are too high or too low.
What’s new in pituitary tumor research and treatment?
Research into pituitary tumors is under way in many university hospitals, medical centers, and other institutions around the country.
Doctors now have a better understanding of the genetic basis of pituitary tumors. This is already leading to improvements in genetic testing for people who are suspected of having multiple endocrine neoplasia, type I (MEN1) or other syndromes. This work is also shedding light on the characteristics of non-functioning adenomas that may lead to new medical therapies for these tumors.
Imaging tests such as MRI scans continue to improve, leading to better accuracy in finding and determining the extent of new and recurrent tumors.
Surgical techniques are improving, allowing doctors to remove tumors with fewer complications than ever before. Radiation therapy techniques are improving as well, letting doctors focus radiation more precisely on tumors and limiting the damage to nearby normal tissues.
Progress is also being made in the medicines used to treat both pituitary tumors and the side effects of some other forms of treatment. For example, growth hormone is now produced by DNA technology and has been approved for treating adults who may not have enough growth hormone after treatment for a pituitary tumor.
As doctors learn more about how cells make hormones, they are finding ways to block their production. This should lead to new drugs to prevent pituitary adenomas from making hormones that upset the balance of the body. One example is a drug called pasireotide (Signifor®), a new somatostatin analog that works directly on ACTH-secreting pituitary tumors. It is now FDA approved to help treat people who have Cushing’s disease as a result of these tumors when surgery is not an option or has not been effective.
Another example is a drug called dopastatin, which combines properties of other drugs already used to treat pituitary tumors: dopamine agonists (such as cabergoline) and somatostatin analogs (such as octreotide). This drug and others like it are still in the earliest stages of testing.