Pituitary Tumors

What is the pituitary gland?

The pituitary gland is a kidney bean shaped structure attached to the base of the brain (behind the nose), where it is protected by a small part of the skull called the sphenoid bone. A normal pituitary gland is small (about the size of a pea) and is responsible for controlling and coordinating: 1) growth and development; 2) the function of various body organs (i.e. kidneys, breasts and uterus); and 3) the function of other glandular organs (i.e. thyroid, gonads, and adrenal glands). The pituitary gland performs these functions by releasing different types of hormones (active substances that travel through the body), which are able to direct the activities of other organs.

The pituitary gland itself is controlled by the hypothalamus, a region of the brain located just above the pituitary. Through their various hormones, the pituitary and hypothalamus control many of the body's automatic functions, as well as play an essential role in growth, development and reproduction. The hypothalamus and pituitary together are known as the neuroendocrine system of the body.

The pituitary gland is made up of two different regions, the "anterior pituitary" - the part of the gland closest to the front of the head - and the "posterior pituitary" - the part of the gland closest to the back of the head. These two parts differ based upon the hormones they release, the types of cells that they contain, and how they develop in the fetus. The anterior pituitary is formed from the same tissue as the pharynx (the upper part of the throat). The posterior pituitary develops from the bottom portion of the brain, and is directly connected to the hypothalamus.

The anterior pituitary comprises approximately 80 percent of the pituitary gland, and is divided into three parts: the anterior lobe, the intermediate zone and the pituitary stalk. The anterior lobe is responsible for the majority of the hormones released into the body's blood stream.

The posterior pituitary develops very early in life and also is divided into three parts. Unlike the anterior pituitary, the posterior pituitary does not make any hormones of its own. Instead, it contains the endings of brain cells (neurons) that arise from specific regions of the hypothalamus. The brain cells in the hypothalamus produce hormones (such as growth hormone, prolactin, adrenocorticotrophic hormone, thyrotrophin stimulating hormone, follicle stimulating hormone and leutinizing hormone, vasopressin, and oxytocin), that are then transported down into the posterior pituitary, where they are stored and later released into the bloodstream.

What hormones are released by the pituitary gland?

The anterior pituitary releases hormones into local blood vessels, which are then transported through the body to reach their target organs. The anterior pituitary is known to secrete eight hormones: growth hormone (GH); prolactin (PRL), thyrotrophin stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), leutinizing hormone (LH), follicle stimulating hormone (FSH), melanocyte stimulating hormone (MSH), and endorphin (beta-END). These hormones are produced by different pituitary cells, which are located in specific regions of the pituitary gland. Certain "master" hormones from the hypothalamus serve as triggers for the release of these pituitary hormones.

The posterior pituitary releases two hormones, vasopressin (ADH) and oxytocin.

What are pituitary adenomas?

Pituitary adenomas are benign tumors (meaning that they are non-cancerous and do not travel to
other parts of the body) that arise exclusively within the anterior pituitary. Although it can be frightening to have a tumor beneath the brain, it is important to note that these tumors are generally non-aggressive, non-cancerous and non-metastatic. Adenomas are basically growths found on or within the pituitary gland. In fact, these tumors are quite common representing 10-15 percent of all intracranial tumors. Adenomas are by far the most common disease affecting the pituitary and are usually found in people in their 30s or 40s. Many of these tumors can be successfully treated. Pituitary tumors can vary in their 1) size, 2) secretory patterns, 3) aggressiveness, and 4) invasiveness (growth of tumor into surrounding brain and skull).

Although most adenomas are benign, small, and slow-growing, some tumors can be associated with disability and occasional death. These problems are related to the sensitive location of the pituitary gland: 1) the internal carotid arteries (supplying blood to the front part of the brain) and large veins are located next to the edges of the pituitary gland, 2) the optic nerves (carry visual information) cross above the pituitary gland, 3) multiple cranial nerves (that control important functions in the head and neck) pass near the pituitary gland, and 4) the pituitary lies near the brain cortex (the outer surface of the brain).

What are the names of the different sizes of adenomas?

Tumors smaller than 10 mm are called "microadenomas," and often secrete certain anterior pituitary hormones. Smaller, functioning adenomas are usually detected early because the increased levels of hormones cause abnormal changes in the body. Approximately 50 percent of pituitary adenomas are diagnosed when they are smaller than 5 mm in size.

Adenomas larger than 10 mm (the size of a dime) are called "macroadenomas," and they usually do not secrete any hormones. These tumors are initially discovered because of the symptoms they produce when they compress nearby brain structures.

How are adenomas generally diagnosed?

When diagnosing an adenoma, the physician will look for signs of endocrine dysfunction (hormonal problems), vision disturbances, and evidence of compressed brain tissue and/or nerves.

Endocrinologic Evaluation. These tests provide an understanding of the hormonal levels within an individual. Baseline blood concentrations can be measured for the different pituitary hormones (PRL, GH, ACTH, TSH, FSH, and LH).

Stimulation testing (second line testing) is then used to differentiate between the possible causes of hormone imbalance, including those caused by pituitary gland dysfunction. These tests often involve the injection of hormones, which induce specific responses by the body. Responses to these tests may indicate if pituitary disease is causing a patient's symptoms, or whether another mechanism is at work.

Third line tests are very specific, and are used to further analyze a particular pituitary adenoma. The third line tests are especially used for Cushing's syndrome (excess ACTH) and acromegaly (excess GH).

Neuroimaging Studies. The most important brain scan for studying pituitary adenomas is the magnetic resonance imaging (MRI) scan, which can provide excellent detail of the location, size, and invasiveness of the tumor. Because of the very small size of the pituitary, use of an "open-MRI" is not as helpful as a "closed-magnet MRI", which is more accurate in image detail.

The computed tomography (CT) scan, while not as clear as an MRI, can also be used in the diagnosis of pituitary adenomas.

Neuroimaging studies are important because they may distinguish adenomas from other types of tumors and diseases that can occur in this region and imitate adenomas. However, the use of MRI/CT alone cannot distinguish between the different types of pituitary adenomas.

Histopathologic Examination. Pituitary tissue is acquired through biopsy at the time of surgical removal. Analysis of the tissue with special stains is the most accurate way to diagnose a particular type of pituitary adenoma.

What are non-secretory adenomas?

Non-secretory adenomas are also called "non-functional", ""silent", and "endocrine-inactive adenomas." These types of adenomas are usually larger than 10 mm when found, and are usually discovered because they do not secrete any hormones. These types of tumors account for 50 percent of the undiagnosed pituitary adenomas present in the general population, and represent 25 percent of tumors that are surgically removed. Twenty-four percent of these adenomas invade into adjacent structures.

What are the symptoms of non-secretory adenomas?

Patients with non-secretory adenomas present with general complaints that can be produced by any mass lesion within the pituitary region. A mass lesion is a nonspecific term that refers to any number of things (tumors, blood collections, infections, etc.) that exert pressure on nearby structures.

The most common of these symptoms are visual disturbances (found in 60-70 percent of patients) most frequently described as a progressive loss of vision in the peripheral visual fields. This deterioration occurs when the enlarged pituitary compresses the optic nerves that carry visual information from the eyes. The vision loss often begins in the upper, outer parts of the visual fields, and can progress to blindness if the growth of the tumor continues unchecked. Patients may also present with "central scotoma," in which there is a loss of vision in the central region of a visual field.

Large adenomas may also present with headaches due to: 1) the adenoma pressing against nearby brain structures, 2) an increase in intracranial pressure (the pressure within the skull, which can compress the brain if the pressure increases), or 3) a blockage of the ventricles within the brain causing hydrocephalus. The ventricular system is a group of connected chambers in the brain, which contain cerebral spinal fluid, that nourish and protect the brain. Symptoms of hydrocephalus include severe headache, fatigue, visual disturbances and coma.

In some rare instances, pituitary neoplasms can also compress adjacent cranial nerves. Patients with such lesions can present with visual difficulties such as blurred vision, loss of visual sharpness, double vision, and/or unequal sized pupils. Very large adenomas can sometimes produce facial numbness or pain through nerve compression.

Extraordinarily large pituitary adenomas can sometimes compress adjacent brain regions. Possible symptoms depend on the affected cortical regions (the outer surface of the brain), and can include memory loss, personality changes or seizures. If the hypothalamus is compressed, many important body functions may be affected as well, including water balance, body temperature regulation, sleep cycles, hunger, levels of consciousness, emotions and behavior. In addition, damage to the hypothalamus may affect the functioning of the pituitary, resulting in a decreased, or sometimes increased, release of pituitary hormones.

It is important to note that the most common syndrome resulting from damage to the hypothalamus or pituitary stalk (the connection between the hypothalamus and the pituitary) is diabetes insipidus. This syndrome results from decreased amounts of vasopressin (ADH) release from the posterior pituitary. Patients with this condition present with frequent urination, dilute urine (clear and watery), dehydration, and increased thirst. The effects of surgery or tumors within the pituitary region cause the majority of cases of diabetes insipidus. Depending on the particular type of injury, diabetes insipidus can be either a short lasting or permanent condition.

In addition, pituitary hypofunction, or decreased hormone release, can result from the compression of normal pituitary tissue of the adenoma. Examples of decreased hormone release include:

1) Hypothyroidism. This condition results from the compression of cells that release thyrotrophin stimulating hormones. Symptoms may include cold intolerance, fatigue, sluggishness, dry skin, deepening voice, coarse hair and facial puffiness.

2) Gonadal Atrophy. This condition results from damage to the pituitary cells that release thyrotrophin stimulating hormones and leutinizing hormones, and causes loss of sexual drive, vaginal and uterine atrophy (thinning of the walls of these organs), disrupted menstruation, small testicles and decreased sperm production and potency.

3) Adrenocorticotrophic Hormone Reduction. Damage to the cells that release Adrenocorticotrophic hormones can produce symptoms of nausea, vomiting, dizziness upon standing, excessive tiredness and fevers.

4) Panhypopituitarism. This condition results when the pituitary no longer secretes any hormones (or secretes them at much lower levels). Patients with this condition may experience decreased sex drive, smooth and pale skin, fine wrinkles around the eyes and mouth, loss of armpit and pubic hair, loss of facial hair, anemia and excessive fatigue.

How are non-secretory adenomas diagnosed?

Patients who present with some of the aforementioned symptoms should be assessed for a potential pituitary adenoma, through endocrinologic testing (hormone testing of the blood and urine) and imaging studies of the brain, such as MRI. Ophthalmologic, or vision, testing also is an important part of the evaluation of the visual changes caused by larger adenomas.

What is the surgical therapy for non-secretory adenomas?

Surgical therapy is the most common and effective treatment for non-secretory tumors. The two main approaches to surgery are the transcranial approach or the trans-sphenoidal approach. The trans-sphenoidal technique involves an incision made at the upper gum line or nasal cavity, which allows the surgeon to approach the tumor through the base of the skull. This is the surgical procedure of choice because of decreased side effects and shortened recovery times, when compared to the older transcranial approach. Patients can often leave the hospital within four days of surgery. The recent use of endoscopic surgery, which uses small fiberoptic tubes to visualize the tumor, may further decrease the length of hospitalization in certain cases.

What types of posterior pituitary tumors are there?

Granular cell tumors are the most common tumors found in the posterior pituitary. They arise from glial cells, which are support cells found in the posterior pituitary. Microscopic, clinically unimportant granular cell tumors are found in approximately 17 percent of the general U.S. population at autopsy, but are very rare in persons under the age of 20. These lesions usually do not cause any symptoms, but occasionally they can compress adjacent brain structures, thereby requiring surgical removal of the tumor.

Gliomas are another form of posterior pituitary tumor. They are quite rare and are usually non-aggressive in nature. They arise from astrocytes, a particular type of glial cell found in the posterior pituitary.

Pituitary metastases are also a form of tumor that occurs in 1-5 percent of all cancer patients. Seventy percent of all metastases to the pituitary (tumor cells that travel to the pituitary from a cancer somewhere else in the body) are found in the posterior lobe. The most common cancers that metastasize are: 1) breast, 2) lung, 3) colon, 4) prostate, 5) lymphoma, and 6) leukemia. Surgical therapy for these tumors usually will not improve survival because the patient has cancer elsewhere in his or her body. Surgical removal of part of the pituitary may be performed if there are symptoms caused by compression on nearby structures.

What are the goals of surgery for hormone secreting adenomas?

Treatment for any pituitary hormone-secreting adenoma has three main goals: 1) remove/shrink any tumor mass that is compressing adjacent structures, 2) remove/inactivate any hypersecreting pituitary tissue in order to restore normal hormone levels, and 3) provide the necessary preoperative and postoperative hormone replacement aimed at returning the body to normal hormone production. Surgery generally accomplishes the first two goals.

What are the different types of surgery for hormone-secreting pituitary tumors?

The two main approaches used are the transcranial approach (through the front of the skull) and the trans-sphenoidal (surgeon makes incision in the upper gums or at the base of the nose). The trans-sphenoidal technique is the preferred surgery, as it decreases injury to the brain, leaves less of a scar, has fewer side effects and a shorter recovery time.

The trans-sphenoidal approach is recommended in 95 percent of all operations performed for pituitary adenomas. This approach can even be used for very large and invasive tumors. This type of surgery can produce long-term control or cure in many microadenomas, but is slightly less successful with larger adenomas.

Most patients with adenomas will experience a decrease in their symptoms following surgery (often significant improvements in vision). The main complications of this surgery, though infrequent, include infections, bleeding, cerebrospinal fluid leakage from the nose, diabetes insipidis, visual loss, double vision, and/or trauma to the internal carotid arteries that can cause stroke or even death.

Usually, only the adenoma is removed, but occasionally a portion of the pituitary gland is removed along with the tumor, resulting in decreased secretion of one or more pituitary hormones. Patients undergoing surgery will commonly take antibiotics and steroids, and expect to leave the hospital within four days following surgery.

Transcranial surgery was the main approach used before the development of the trans-sphenoidal technique. The incision is usually made on the right-side of the head, and will leave a scar. Reasons for the surgeon to perform transcranial surgery include: 1) hard, fibrotic tumors that cannot be easily removed through the trans-sphenoidal approach, 2) residual tumor masses that cannot be removed through the trans-sphenoidal technique, 3) a "dumbbell-shaped" pituitary adenoma, and 4) other tumors found in the pituitary region, including craniopharyngiomas and meningiomas. The advantage of this surgery is the greater visualization of pituitary adenomas that have grown out of the confines of the normal pituitary gland and into nearby structures. The disadvantages of this surgery are that the surgeon must expose the brain, and that there is a decreased visibility of the pituitary. The complications of this surgery include damage to the brain, bleeding, infections, and vision. In addition, this type of surgery will require a longer hospital stay.

Note: The Annual Meeting press kit can be found in the Media Center Section of the AANS Web site at: http://www.neurosurgery.org/aans.

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