How are pituitary adenomas treated?

Surgery

Currently, the most common therapy for pituitary adenomas (excluding prolactin-secreting adenomas, also known as prolactinomas) is surgical resection. For non-secreting macroadenomas, surgery removes excess tissue and relieves pressure from the adenoma on surrounding tissues. For secreting adenomas, surgery often results in a rapid drop in the excessive hormone production.

Surgery for pituitary tumors can be performed in several different ways. The most common approach is the transsphenoidal approach . In this procedure, an incision is made on the inside of the upper lip just above the teeth, or along the septum of the nose. The pituitary gland is accessed by cutting through the bond of the sphenoid sinus , which lies behind the nose and just in front of the pituitary gland. For microadenomas, this procedure has high overall cure rates with few complications. Occasionally, this surgery can lead to decreased hormone production from the pituitary gland, leaks of cerebral spinal fluid leading to meningitis, and possible loss of vision. These complications are rare and occur in less than 1% of transsphenoidal surgeries performed by an experienced neurosurgeon. The transsphenoidal approach is less optimal for larger tumors, particularly macroadenomas that are very fibrous or extend too far towards the back of the head.

Recently, more pituitary surgeries have been performed endoscopically. Endoscopic surgery is performed by using a fiberoptic camera (the endoscope) to access the pituitary fossa (usually through the nostril in a transsphenoidal approach). Small instruments are passed through the small hole made by the endoscope and used to remove the pituitary adenoma. This procedure works well for small tumors and has the advantage of being less invasive than a transsphenoidal surgery, with a quicker patient recovery time and a low complication rate. However, this procedure may not be appropriate for larger tumors or tumors that are not in the appropriate position.

For larger tumors with a large amount of extension beyond the normal pituitary gland, a craniotomy can be performed. A craniotomy requires the neurosurgeon to cut through the bones of the skull to access the pituitary gland. Although it may be the only type of surgery possible in some cases, there is a higher risk of neurologic complications and a longer recovery time for the patient as compared to the other surgeries.

With any surgery to the pituitary gland, the development of central diabetes insipidus is fairly common. In diabetes insipidus, the pituitary gland does not produce enough anti-diuretic hormone (ADH), which leads to excessive loss of water in the urine. In most cases of post-operative diabetes insipidus, the problem goes away by itself after one to two weeks.

Occasionally, however, this problem can be permanent. Treatment requires taking replacement ADH (also known as vasopressin), usually as a nasal spray.

External Beam Radiation Therapy

Radiation therapy can also be used in the treatment of pituitary adenomas, although in the majority of cases, it is not used as the first line of treatment. The radiation comes in the form of high energy x-rays that are delivered to the patient only in the areas at highest risk for cancer. These x-rays are similar to those used for diagnostic x-rays, only of a much higher energy. The high energy of x-rays in radiation therapy results in damage to the DNA of cells, causing the tumor cells to die. Although the overall control of pituitary tumors with radiation therapy is high, radiation does not remove the pressure that macroadenomas can exert on surrounding structures as surgery does, and hormone levels fall more slowly after radiation therapy than they do after surgery. In most cases, radiation therapy is reserved for patients who have disease left behind after surgical resection, for patients who have their pituitary adenoma come back after surgery, for patients whose adenomas are in a location such that surgical resection would carry a high rate of complications, or in patients who are not medically operable.

Standard radiation (also called conventional radiotherapy) for pituitary adenomas is given daily, Monday through Friday, usually for 5 to 6 weeks. The radiation treatments themselves are short, lasting only a few minutes. Like diagnostic x-rays, radiation treatments cannot be seen, heard, or felt, and they do not hurt. Generally, the side effects of treatment are limited to the areas being treated. Most commonly, standard radiation treatment for pituitary adenomas can result in loss of hair and fatigue. Because the pituitary gland sits very closely to the optic nerves and optic chiasm, there is a risk that radiation treatments can cause loss of vision, although this is unusual in the hands of a skilled radiation oncologist. Compared to surgery, patients receiving radiation can experience hypopituitarism , where the pituitary has decreased production of one or more of the hormones that it usually releases. If this occurs, these hormones can be replaced in the form of medication. Finally, although the risk is low, radiation for pituitary tumors may cause cancers to form in the radiation field years after the radiation has been given.

Stereotactic Radiosurgery

Stereotactic radiosurgery is a way of delivering radiation therapy in a very precise way. Often, this is done in order to treat a tumor with large doses of radiation over a few days, or even in a single treatment, rather than spreading the treatment out over a number of days as is done with standard radiation therapy. When performed in other parts of the brain, this technique can deliver high doses of radiation to a specific area of the brain while reducing the amount of radiation that is delivered to normal, healthy brain tissue. Stereotactic radiosurgery has been tried in pituitary adenomas, and compared to standard radiation therapy, it results in more rapid decrease in hormone levels of secreting adenomas. However, because higher doses are delivered with each treatment, a higher rate of complications has been seen with stereotactic radiosurgery, particularly with regards to damage to the optic nerves and the optic chiasm. For this reason, stereotactic radiosurgery is not often used to treat pituitary adenomas. Occasionally, stereotactic radiosurgery can be used in situations where a pituitary adenoma has recurred after previous treatment.

Medical Therapy

For some pituitary adenomas that secrete hormones, treatment with medication rather than surgery or radiation can be effective, and is often the first treatment tried for these types of adenomas. For pituitary adenomas that produce the hormone prolactin, the medication most commonly used is bromocriptine (Parlodel). Other drugs such as cabergoline (Dostinex), lisuride , and pergolide mesylate have also been used with some success. These drugs are similar to a chemical normally produced in the brain called dopamine that normally prevents the pituitary gland from producing prolactin until it is needed. These drugs result in reduced prolactin production in the pituitary adenoma and can actually lead to shrinkage of the tumor in the majority of patients. The rate at which these tumors shrink in response to medical therapy can be very variable, taking anywhere from days to months. If the medication is stopped, the adenoma will resume producing prolactin and can grow again. Therefore, medical therapy as the only treatment for a prolactin-secreting pituitary adenoma requires lifelong treatment.

Approximately 10% to 20% of patients taking bromocriptine experience side effects from treatment. These can include nausea, vomiting, dizziness, low blood pressure, and headaches.
Pituitary adenomas that produce a few other types of hormones can also be treated with medication. Adenomas that secrete growth hormone can be treated with drugs such as octreotide and lanreotide . These drugs can also be used to treat some adenomas that secrete thyroid-stimulating hormone. While these drugs are being used in several studies, surgery still remains the treatment of choice in most of the US for these types of adenomas, with medical treatment reserved for cases where surgical resection has been unsuccessful.

Observation

Occasionally, small non-secreting tumors are found in the pituitary gland when a patient is undergoing workup with an MRI scan for an unrelated reason. In these cases, where there are no symptoms from the adenoma, it is reasonable to simply follow these tumors with periodic physical examinations and MRIs.

What are the treatment options for malignant pituitary carcinoma (cancer)?

In general, treatment with a combination of surgery and radiation therapy is used for pituitary carcinoma. These are rare cancers, and unfortunately the ultimate outcome with either of these modalities is often poor, especially in the setting of disease that has spread to other part of the central nervous system (metastasized). Chemotherapy has been tried but has demonstrated little benefit. It is occasionally used to help palliate symptoms from pituitary carcinoma that has metastasized.