The bean-sized pituitary gland or "master gland" is extremely important in regulating the function of many other glands and organs of the body . It lies behind and between the eyes at the base of the brain, just beneath the hypothalamus to which it is connected by a thin stalk.
The pituitary gland is controlled by substances (releasing or inhibitory factors) that are sent by the hypothalamus. The pituitary gland, in turn, secretes hormones into the bloodstream. Most of these hormones are chemical messengers that instruct various glands to secrete their own hormones.
Hormones control or regulate many different bodily functions, such as how bones and muscles grow, secual development and the ability to fight disease and stress. In addition to performing their various tasks around the body, these hormones complete a feedback loop by affecting (usually inhibiting) the hypothalamus' production of releasing or inhibitory factors. "Functioning" or hormonally-active pituitary tumors fall into this broad category.
The pituitary gland is divided into two main parts: The anterior pituitary (adenohypophysis) and the psterior pituitary (neurohypophysis). Two-thirds of all pituitary tumors occur in the anterior or front portion of the gland.
These tumors are named after the hormone they secrete. The anterior pituitary secretes the following hormones:
• Prolactin (PRL) - PRL tumors are the most common pituitary tumor, accounting for between 35 and 45 percent of all cases. In women, PRL stimulates the breasts to produce milk. Excess PRL prodcution causes inappropriate production of milk (galactorrhea), irregular menstual cycles or cessation of menses (amenorrhea) and infertility. In men, excess PRL leads to impotence and infertility. This pituitary tumor occurs more frequently in women and is commonly found during their childbearing years. In men, it is usually discovered after age 50.
• Growth Hormone (GH) - About 20 percent of all pituitary tumors are GH secreting tumors and they are more common in men than women. GH actually stimulates the liver to produce another hormone, Somatomedin-C or Insulin-Like Growth Factor-1 (IGF-1). This hormone, in turn, regulates the growth of bones, muscles and many other organs. In children, excess production leads to gigantism. In adults, it leads to enlargement of the hands, feet and jaw (acromegaly). In addition, these patients may suffer from diabetes mellitus, hypertension, heart disease and arthritis. Some develop colon polyps and cancer.
• Adrenocorticotropic Hormone (ACTH) - ACTH stimulates the adrenal gland, located on top of each kidney, to secrete cortisol (a glucocorticosteroid). Among other things, cortisol helps the body deal with stress and diseas. Excess cortisol (Cusing's syndrome) causes excessive fat buildup in various areas, including the face ("moon face"), neck ("buffalo hump") and abdomen. Legs and arms are usually thin (centripetal obesity). There's thin skin, easy bruising, diabetes mellitus, hypertension and excessive hair growth (hirsutism). Depression is common. Cushing's syndrome can be a result of many things, including excessive intake of commonly prescribed medications containing steroids. When it is the result of an ACTH-secreting pituitary tumor, it's called Cushing's disease. ACTH tumors represent 15 percent of pituitary tumors. They are more common in women than men.
• Thyroid Stimulating Hormone (TSH) - TSH stimulates the thryroid gland to secrete thyroid hormone, which regulates metabolism. Excess production leads to hyperthyroidism, which is manifest by rapid hear beat, hypertension, irritability, weight loss and intolerance to heat. These tumors are rare.
• Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) - In women, FS and LH help regulate egg production by the ovaries and control the menstrual cycle. In men, these hormones help regulate the testes' production of sperm and testosterone. Excess production can lead to abnormalities with these functions. These tumors are also rare.
Approximately 10 to 15 percent of all brain tumors are pituitary adenomas. While these tumors of glandular tissue are almost benign, they can be difficult to remove completely.
Non-functioning or non-secreting tumors are characteristically slow-growing. If they are not compressing the visual nerves, such tumors are often merely observed.
However, some non-functioning pituitary tumors may compress or damage the normal gland, leading to insufficient production of one or more hormones, or compress visual nerves. These tumors can grow to be quite large as they do not signal their presence with an excess of hormones. They are usually found only when symptoms of compression are noted.
Loss of peripheral vision is often the first sign. The patient may bump into doorways frequently or have repeated minor motor vehicle accidents.
Symptoms of pituitary insufficiency are generally related to lack of cortisol, thyroid hormone and sex steroid hormone production. These varied symptoms include decreased energy, hair loss, low blood pressure, weight gain, impotence and menstrual irregularity.
Microsurgery is commonly used to treat a non-functioning tumor. The neurosurgeon may use the transsphenoidal route at the base of the cranium or a craniotomy (removal of part of the skull). Afterward, if the residual tumor is small and visual nerves are not compressed, close observation may be all that's needed. If there is still compression of the visual nerves or if a previously resected tumor recurs, the surgeon may recommend further surgery, radiosurgery, a one-day treatment or fractionated radiation therapy, involving several days or weeks of treatments.
In selected cases, Gamma Knife radiosurgery has the advantage of delivering a high dose of radiation in a single fraction while minimizing the risk of damage to the nearby visual nerves and normal pituitary gland. Also, Gamma Knife offers the convenience of a single treatment compared to several weeks of fractionated radiation therapy. Overall, Gamma Knife radiosurgery has a very high chance of preventing further tumor growth -- and in some cases shrinking the residual tumor -- with very little risk of visual loss or damage to the hypothalamus.
While Gamma Knife radiosurgery can be utilized as either the primary or secondary treatment for pituitary tumors, it is generally reserved as second-line therapy after residual or recurrent tumor is noted.
Patients with functioning or homone-secreting tumors generally require immediate relief of their symptoms, which may include hypertension and diabetes. Microsurgery is usually used as the primary treatment.
When a functioning tumor is incompletely removed or recurs, further treatment is imperative to try to stop excess hormone secretion. In these cases, the residual tumor is usually small and can often be visualized on an MRI. Gamma Knife radiosrugery is ideally suited for this type of situation. With high-quality imaging and complex treatment planning using sophisticated plugging patterns, a very high dose of radiation can be delivered to the tumor while limiting the visual nerves to a very low dose, generally less than 8 Gy.
When the tumor can be separated from the normal gland on the MRI, the risk of hypopituitarism (loss of normal pituitary hormone function) is significantly lower than with fractionated radiotherapy. With Gamma Knife radiosurgery, the elevated hormone levels generally decrease within six to 12 months, generally a little quicker than with fractionated radiotherapy. Depending on the type of tumor, hormone secretion returns to normal in 50 to 90 percent of cases.
Radiosurgery is not recommended for tumors elevating and compressing the visual nerves because of the risk of injury to these nerves. However, there has been consideration given to a clinical trail looking at microsurgery versus Gamma Knife radiosurgery as the primary treatment of functioning pituitary tumors.
Prolactin secreting tumors can often be successfully treated with medication only. When this does not benefit the patient and tumors are small, radiosurgery may be considered.
In cases where microsurgery has successfully reduced the tumor near the optic apparatus, Gamma Knife may be used to treat the residual tumor.
Radiosurgery on linear accelerator (Linac) based equipment is less commonly attempted with pituitary tumors because of the close proximity of the pituitary to the optic chiasm and the brain stem. Some Linac authorities advocate a "fractionated radiosurgical approach" where a relocatable frame is used to deliver a low dose radiosurgical treatment once a week for three to six weeks. There is little data comparing these different approaches.
The pinpoint targeting of the Gamma Knife makes it the preferred instrument when treating pituitary tumors radiosurgically.
Gamma Knife radiosurgery is an accepted part of the complex treatment program for the management of pituitary tumors. As of June 1997, more than 6,000 people have received Gamma Knife radiosurgery for their pituitary tumors.
Dr. Alan Appley, a neurosurgeon, is in Layfette, LA. He has been a principal investigator on a protocol involving the Gliadel Wafer for malignant brain tumors, a co-invetigator on a Phase I/II study utilizing an antiglioma compound (hypericin) and participates in other multi-institutional protocols. He may be reached at +337-235-7743.
Radiosurgery Practice Guideline Initiative
Stereotactic Radiosurgery for Patients with Pituitary Tumors
Practice Guideline Report #3-04
ORIGINAL GUIDELINE: April 2004
MOST RECENT LITERATURE SEARCH: April 2004
This practice guideline, together with a report on "Pituitary Tumors: Overview" is an originalguideline approved by the IRSA® (International RadioSurgery Association) Board of Directors and issued in April 2004.