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New Approaches to Managing Tumors of the Pituitary Gland Offer Patients Hope...

From OncoLog, September 2004, Vol. 49, No. 9

New Approaches to Managing Tumors of the Pituitary Gland Offer Patients Hope
by Ellen McDonald

Patients with tumors of the pituitary gland generally find themselves in a uniquely frustrating position: On the one hand, they learn the good news that many of these tumors are asymptomatic and that death from such tumors is very rare. On the other hand, they soon learn that they face a lifetime of potentially debilitating illness often necessitating multiple interventions, lifelong hormone replacement therapy, and long-term follow-up care.

At The University of Texas M. D. Anderson Cancer Center, several advances in treating pituitary tumors offer new hope to patients: Successful surgical resections of these tumors are becoming more common, a clinical trial comparing two drugs used in the medical treatment of acromegaly is under way, and the projected opening of the institution’s proton therapy facility in 2006 may provide an improved means of irradiating pituitary tumors without damaging normal surrounding tissues.

Understanding the pituitary tumor

Tumors of the pituitary gland are generally slow-growing benign adenomas that are classified as either functional (60%), meaning that they hypersecrete one or more hormones, or nonfunctional (40%), meaning that they secrete no hormones but instead are just masses of cells. These tumor masses can compress the pituitary gland itself, which can cause hormone deficiency, or adjacent structures such as the optic nerve, which can lead to disturbances in and loss of vision.

“Although pituitary tumors generally do not metastasize and do not have mitotic features, they can sometimes behave in a very locally aggressive manner,” said Rena V. Sellin, M.D., a professor in the Department of Endocrine Neoplasia and Hormonal Disorders at M. D. Anderson. “Although usually benign, they can recur again and again.”

According to Steven G. Waguespack, M.D., an assistant professor in the Department of Endocrine Neoplasia and Hormonal Disorders,there are three questions that should be asked when treating patients with these tumors:

1) Is the tumor making a hormone that is causing a clinical syndrome—growth hormone in acromegaly, adrenocorticotropic hormone in Cushing’s disease, or prolactin, which can cause hypogonadism (low estrogen or testosterone levels) and abnormal breast milk production?;

2) Is the tumor preventing the pituitary gland from working normally, thereby causing one or more hormone deficiencies?; and

3) Is the tumor mass causing visual loss or affecting other cranial nerves?

The etiology of pituitary tumors is generally unknown, and their incidence has been variously reported. “The incidence of pituitary tumors across the board is about one in seven people,” said Ian E. McCutcheon, M.D., a professor in the Department of Neurosurgery at M. D. Anderson and president of the Pituitary Network Association who recently helped conduct a meta-analysis of published studies on the incidence of these tumors, which appeared in Cancer. However, only 5% of people with pituitary tumors will ever have any symptoms related to the tumor.

Treatment approaches

Treatment of benign pituitary tumors consists of surgery, radiotherapy, medical therapy, or a combination of these methods. The indications for surgery depend on the size and type (functional or nonfunctional) of the pituitary tumor involved. “Usually, with the functional ones, we start with an operation to try to remove as much of the tumor as we possibly can because the disruption of excess hormone is typically causing profoundly negative changes for the patient,” observed Dr. McCutcheon. An exception to surgical treatment of functional tumors occurs in prolactinomas, which are generally responsive to medical therapy. “In the nonfunctional category,” Dr. McCutcheon continued, “the reason to operate is to protect the optic system from a large or expanding tumor.”

According to Dr. McCutcheon, approximately 95% of the operations performed on pituitary tumors at M. D. Anderson use a transsphenoidal approach, following a route along the inside of the nose; the remaining 5% are craniotomies. Dr. McCutcheon pointed out that the first transsphenoidal surgery in Texas was performed at M. D. Anderson by Milam E. Leavens, M.D., former Ashbel Smith professor emeritus of neurosurgery in the Department of Neurosurgery (and Dr. McCutcheon’s predecessor).


Lauren A. Langford, M.D., an associate professor in the Department of Pathology at M. D. Anderson, noted that 10% to 15% of primary brain tumors diagnosed each year are pituitary tumors. Pathologists determine which hormones are being produced by the tumor cells and what is in the cells “to complement the data obtained by the endocrinologist’s full battery of hormonal tests,” she explained. In addition, results from immunohistochemical stains can be obtained quickly; a special reticulum stain performed during surgery to see whether the subunits of the pituitary gland are intact takes about 15 minutes. “If they are intact, then we think the specimen is probably normal tissue,” she said. This information can be invaluable to the operating surgeon, not to mention the patient. Pathologists also use the fact that pituitary adenomas shed their cells to distinguish them from normal tissue.

Dr. Langford shares the following advice with her trainees: “Pituitary tumors are very difficult; spend a lot of time on them, look at a lot of them, because you have a person’s whole hormonal axis in your hand.”

Treating acromegaly

Patients with acromegaly have two to four times the death rate of those without the disease and generally live 10 years fewer, said Dr. Waguespack. “So we try to be as aggressive as possible to treat their disease.” He noted that although surgery can be curative for easily resectable microadenomas (tumors < 1 cm), most patients with acromegaly actually have larger tumors. “For these adenomas, particularly when the tumor is causing visual compromise, surgery is usually undertaken not so much in hopes of a cure but to alleviate the symptoms caused by the tumor size itself,” he said. Subsequent medical management is almost always required.

According to Dr. Waguespack, three types of medicine are available to treat acromegaly: The oldest drugs are the dopamine agonistic agents, which are used to treat prolactinomas and are effective in fewer than 15% of cases of acromegaly. The second type of agent is a somatostatin analogue called octreotide, which inhibits the pituitary somatotroph from making growth hormone. “This drug, which has been the most tried and true, is effective in lowering growth hormone levels in 65% of patients with acromegaly who receive it,” said Dr. Waguespack. The third type of medicine is the drug pegvisomant, approved for use in 2003, which does not have any direct effect on the tumor but blocks growth hormone at its receptor level, telling it not to make insulin-like growth factor 1, which is the main mediator of growth hormone action. According to Dr. Waguespack, studies of this drug have shown it to be more than 90% effective.

In a randomized clinical study, Dr. Waguespack is directly comparing pegvisomant with octreotide for the treatment of patients with acromegaly who have never received any medical therapy for their disease. This phase IV trial is the first comparative study of the two drugs used most often in the treatment of the disease. Dr. Waguespack expressed some concern about the “theoretical risks” of pegvisomant, in particular the possibility that when growth hormone is blocked at the receptor level, the pituitary tumor may eventually grow larger. “This risk does not typically exist with octreotide, which can cause tumors to shrink,” he said.

Dr. Waguespack also spoke enthusiastically about the improved ways of delivering radiotherapy to pituitary tumors that are now available, including forms of stereotactic radiosurgery: Both gamma knife and linear accelerator technologies provide targeted therapy to the tumor site, thus minimizing the radiation exposure of adjacent tissue and potentially eliminating the late effects of conventional radiotherapy, such as secondary brain tumors, neurocognitive effects, and hypopituitarism. Radiosurgery is performed on patients with pituitary tumors at M. D. Anderson by Dr. McCutcheon and his colleagues in the Division of Radiation Oncology. A high degree of precision can be achieved by using magnetic resonance imaging overlay and other technologies now available, but Dr. Waguespack reserved his highest praise for proton beam therapy and its promise of effecting a cure without damaging surrounding tissues. However, he cautioned, this is an area that has not been well studied in acromegaly and requires further clinical investigation.

Recently, Dr. Waguespack has seen a number of patients in their 20s with acromegaly. He does not relish the thought of placing them on 50 or more years of expensive medication: “In the future, particularly with younger patients, we are going to have to rethink acromegaly treatment algorithms, incorporating newer medications and technologies to actually attempt to cure patients of their acromegaly.”

The continual improvement in surgical techniques, the advances in medical therapy, and the promise of new types of radiotherapy will doubtless provide those treating patients with pituitary gland tumors with many more options for managing and perhaps even curing the disease.

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