The pituitary is the master control center of hormones in the body. It is located in a small crevice called the sella turcica at the base of the skull. The sella turcica is located underneath the optic chiasm, which is the crossing point of the two vision nerves (optic nerves). The normal pituitary gland produces several important hormones: adenocorticotrophic hormone (ACTH) stimulates the adrenal gland; thyroid stimulating hormone (TSH) stimulates the thyroid gland; luteinizing hormone and follicle stimulating hormone (LH and FSH) interact with the sexual organs; growth hormone (GH) is involved with sugar metabolism and cell growth; and prolactin (PRL) affects lactation.
Pituitary adenomas are slow growing, benign tumors of the pituitary gland. They represent 10-15percent of all brain tumors. Those that are small (less than 1 cm in largest diameter) are called microadenomas, while larger tumors (greater than 1 cm) are commonly called macroadenomas. Pituitary tumors can also be divided into functioning and non-functioning tumors. As the classification implies, functioning tumors produce hormones, often in large, unregulated amounts. Correspondingly, non-functioning tumors do not produce significant amounts of hormones.
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The Presenting Symptoms of Pituitary Adenoma
Symptoms from pituitary adenomas can be classified as follows:
Overproduction of hormones:
The specific symptoms experienced by a patient will depend on the type of hormone that is being overproduced. A tumor that produces large amounts of ACTH causes Cushings disease, which leads to obesity, high blood pressure and muscle weakness, among other symptoms. A prolactinoma is a pituitary adenoma that produces large amounts of prolactin. Symptoms of this include irregular menstruation, sexual dysfunction and breast discharge. A growth hormone producing tumor leads to acromegaly, a condition characterized by progressive enlargement of hand and foot size and an alteration of facial features.
A non-functioning adenoma can still lead to hormonal problems. It does so by compressing the pituitary gland and results in a decrease or cessation of normal hormone production by this organ.
A large tumor can grow upwards out of the sella turcica and compress the optic nerves (optic chiasm). Frequently, this leads to a specific form of “tunnel vision” called bitemporal hemianopsia.
Non-specific symptoms: Sometimes a sizable pituitary adenoma can lead to headaches or a sensation of pressure or fullness behind the eyes. Rarely, bleeding into a tumor can lead to severe headaches and double and blurring vision (pituitary apoplexy).
Patients suspected of having a pituitary adenoma should undergo at least two tests. The first is a magnetic resonance imaging scan (MRI), with specific views of the sella turcica. This test provides the anatomic information to determine whether there is compression of the optic chiasm or invasion of neighboring structures, such as the cavernous sinus. The second test is a full endocrinological evaluation to determine whether hormone levels have been affected by the tumor. If the tumor is large, then a visual evaluation, including a visual field examination, becomes important. This test will reveal whether the tumor has affected the optic nerves or chiasm.
Medical treatment is available for pituitary adenomas that overproduce prolactin and growth hormone. For prolactinoma, bromocriptine is quite effective in lowering prolactin levels in a patient’s blood and shrinking the tumor. Acromegaly, caused by an overproduction of growth hormone, can be treated with octreotide. However, growth hormone secreting tumors rarely respond as well to octreotide as prolactinomas do to bromocriptine treatment.
For all other symptomatic adenomas, the “gold-standard” therapy is surgical removal of the tumor. The goal of surgery is to remove as much of the tumor as is safe, thereby eliminating pressure on the optic structures, and removing those cells that are overproducing hormone. Most pituitary surgeries do not require cutting on the scalp and drilling into the cranium. Instead, the most common surgical approach is called “transsphenoidal,” because the surgery is performed through the sphenoid sinus, which is an air-filled space behind the nose. The incision is made either under the lip or inside the nose. By working behind the region of the nose and attacking the tumor from underneath the sella turcica, the tumor can be removed. An endoscopic-assisted variant of the transsphenoidal procedure is becoming increasingly popular. This method of removing pituitary adenomas is less invasive. It utilizes a small endoscope to provide a surgeon with a small but adequate view of the operative site. With this later operation, hardly any incision is needed.
The major risks of transsphenoidal surgery include injury to the carotid arteries on either side of the tumor; the optic chiasm on top of the tumor, and the normal pituitary gland, which can often be indistinguishable from the tumor. When the normal pituitary gland does not function properly after surgery, the patient may require life long hormone replacement.
Not all patients with pituitary tumors need treatment. Sometimes, an “incidental” pituitary microadenoma is discovered on an MRI scan done for other reasons. In such a case, a period of observation is a reasonable alternative approach. Treatment may only be needed when the microadenoma becomes enlarged.
Radiation Treatment and Radiosurgery
If surgery is unable to remove the entire tumor, then radiation treatment may be necessary to control the tumor and prevent it from growing. Radiation may also be an option for patients who are medically unsuitable for surgery or do not want to have surgery.
Conventional radiation treatment directs a small number of radiation beams toward the entire region around the sella turcica and pituitary gland. This technique results in a significant area of normal tissue being included in the “treatment field.” To compensate for this, conventional radiation treatment is given in daily doses over several weeks. Such therapy is generally very effective in preventing the tumor from growing. For hormone-producing tumors, it is also effective in gradually lowering the hormone levels over many years. Despite the fact that with conventional radiotherapy the optic chiasm receives as much radiation as does the tumor, the risks of visual complications are very low. However, the same cannot be said about normal hormonal function. Since both the pituitary and the hypothalamus (another important hormone control center) receive radiation during treatment, nearly half the patients treated with conventional radiation will eventually develop abnormally low hormone levels (hypopituitarism).
Radiosurgery is a new option for treating pituitary adenoma. By focusing the radiation on only the tumor, this form of treatment minimizes the anatomical spread of radiation to normal brain. Emerging data indicates that radiosurgery may be more effective than conventional radiation in lowering abnormal hormone production, and does so over a shorter time interval.
Most radiosurgery techniques, like surgery itself, require treatment to be delivered as a one-time procedure. However, some of the unwanted side-effects of radiation, including the most feared, visual loss, may be accentuated by delivering the radiation all in one day rather than over several sessions; this risk of radiation injury is greatest in those patients where the pituitary is close to or involves the optic chiasm or hypothalamus. In higher risk patients, the risk of injury to critical brain structures may be reduced by staging the radiosurgical ablation.
Benefits of CyberKnife® Radiosurgery
CyberKnife© radiosurgery treatment of pituitary adenoma melds the advantages of both conventional radiation and radiosurgery. Since it is radiosurgery, the area targeted for treatment is minimized to the region of the adenoma only. Perhaps even more importantly, CyberKnife® radiosurgery can be delivered in divided doses just like conventional radiation. Such treatment is termed fractionated stereotactic radiotherapy (FSR) or staged radiosurgery.
Use of the CyberKnife© further lessens the radiation risk to the sensitive structures around the tumor, such as the optic chiasm and hypothalamus. CyberKnife® fractionated stereotactic radiotherapy is also wellsuited for treating a pituitary adenoma that has invaded the cavernous sinus on either side of the sella turcica. The cavernous sinus contains nerves that control eye movement and facial sensation. Because the nerves traverse the field of radiation, fractionated treatment may lessen the risk to those nerves.
Who Should get CyberKnife® Radiosurgery?
There is a group of patients with pituitary adenoma that is particularly suited to undergo CyberKnife® radiosurgery:
- Patients with small tumors that overproduce a pituitary hormone
- Patients who have residual tumor after transsphenoidal surgery
- Patients with hormone-producing tumors, who continue to have higher than normal hormone levels after surgery
- Patients with adenoma that has invaded the cavernous sinus
- Patients who are either unwilling or unable to have transsphenoidal surgery