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An Introduction to Pituitary Adenomas

The Pituitary GlandThe Pituitary Gland
The pituitary gland is a pea-sized organ located at the base of the brain, just above the roof of the mouth behind the nasal cavity. It is connected to a part of the brain called the hypothalamus, which is important in the regulation of pituitary gland function. Most pituitary adenomas arise in the part of the gland known as the anterior pituitary. The anterior pituitary comprises approximately two-thirds of the entire gland and is composed of five different types of cells. Each cell type makes one or two specific hormones that are released into the bloodstream and are transported to various organs throughout the body, such as the liver, adrenal glands, thyroid gland and reproductive organs. These hormones include prolactin, growth hormone, adrenocorticotropic hormone (referred to as ACTH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). When the pituitary hormones reach their target organs, these organs are stimulated to release hormones of their own that can then travel to the hypothalamus (among other places). Depending on the needs of the body, the hypothalamus will secrete factors that either stimulate or inhibit pituitary hormone production. It is in this way that the pituitary gland, along with the hypothalamus and target organs, regulate growth, response to stress, sexual development, and many other bodily functions.


What is a Pituitary Adenoma?
Pituitary adenoma is the medical term for a tumor of the pituitary gland. The word adenoma specifically means tumor of glandular tissue. Pituitary adenomas are quite common in the general population. It is estimated that around 20% of all individuals will develop a pituitary tumor at some point during their lifetime, though many do not cause any problems and are never diagnosed. Most pituitary tumors are not capable of metastasis (spreading to distant sites throughout the body) and are therefore referred to as benign. Two-thirds of pituitary adenomas will remain completely confined to the pituitary gland. Approximately one-third will expand into tissues that are in the immediate vicinity of the pituitary gland, such as the brain. Less than one percent of all pituitary adenomas are able to metastasize throughout the body and are referred to as malignant. Pituitary tumors occur in every age group but are rarely diagnosed before age twenty.

Other Conditions Involving The Pituitary Gland

Pituitary Cysts
Of the several types of cysts that can form in the pituitary region, arachnoid cysts and Rathke's cysts are the most common. Some pituitary tumors may partially degenerate to form cystic structures as well. Both arachnoid and Rathke's cysts are benign and only require treatment if they become larger and pose a risk of visual loss from compression of the optic pathway. Transsphenoidal microsurgery is generally the recommended treatment. Although treatment results in improvement of symptoms, the cyst sometimes recurs.

Empty Sella

The empty sella is not a disease but rather an anatomical description of the pocket (the sella) in which the pituitary gland lies. MRI and CT scans can demonstrate this anatomy. There may be several causes for empty sella and in rare instances it may be associated with CSF leakage, although this is not necessarily the cause of the leakage. If CSF leakage is present, treatment with transsphenoidal surgery may be necessary to seal the leak.

Infections and Inflammatory Conditions

Infections are a rare cause of pituitary disease. Bacterial abscesses and infections such as tuberculosis can occur and generally are treated with surgery and antibiotics.
Sometimes the pituitary gland may be affected by inflammatory disorders. A common example is inflammation of the pituitary gland characterized by infiltration of the gland with lymphocytes (called lymphocytic hypophysitis). It is difficult to recognize the difference between this condition and a pituitary adenoma, but it can be identified at surgery and treated with glucocorticoids.

Non-pituitary Tumors in the Sella
Most pituitary gland tumors will be adenomas but in rare cases other tumors may be found in or involving the gland. Patients with systemic cancer may develop metastases to the pituitary gland. Tumors growing from the structures next to the pituitary gland (such as chordoma, chondrosarcoma, and meningioma) may look like a pituitary tumor, as may certain vascular lesions such as an aneurysm of the carotid artery. Fortunately, MRI scanning greatly assists in distinguishing these lesions from the common pituitary tumor. Now only rarely will carotid angiography be required in the work-up for pituitary disorders.


Classification of Pituitary Adenomas
Pituitary adenomas may or may not secrete hormones. The majority of tumors do secrete hormones and can be classified by which hormone(s) they are producing.

The most common type of pituitary tumor is the prolactin-secreting prolactinoma. These account for nearly 30% of all pituitary tumors.

The second most prevalent type, comprising approximately 25% of pituitary tumors, is called a null cell adenoma. Null cell adenomas are considered non-functioning because they do not produce any hormone.

Growth hormone-secreting tumors, seen in about 10-15% of patients, are associated with acromegaly, a clinical syndrome that involves a thickening of the bones of the hands, feet, cheeks, and jaw.

Another 10-15% of pituitary adenomas are accounted for by ACTH-secreting tumors, which are often the cause of Cushing's disease.

Some pituitary tumors are also capable of secreting more than one hormone. The most common multihormonal tumor secretes both growth hormone and prolactin. Tumors that secrete TSH or FSH and LH are not frequently seen.

The Genetics of Pituitary Adenomas

How a Pituitary Adenoma Forms
An individual's genetic information is contained in his or her DNA (deoxyribonucleic acid). In humans, the DNA in each cell is tightly wound and packaged into 46 chromosomes. Segments of DNA that are responsible for making the proteins a cell needs to function are called genes. Each person has two copies of every gene in every cell in the body: One from his mother and one from his father. Since every cell in the body has the same genes, different types of cells are distinguished by the set of genes they actually use. The particular set of genes used by a pituitary cell makes that cell a pituitary cell rather than, for example, a muscle cell.

At certain times during the life of a human, it is necessary for cells to grow and divide. In order for cells to divide, they need to make a copy of their DNA. In the process of copying the DNA, mistakes can be made. These mistakes, referred to as mutations, are often repaired and do not cause any problems. However, a mistake will occasionally occur in a gene that causes that cell to divide uncontrollably. The excessive cell growth and division that results from this mistake, or gene change, may result in the formation of a tumor. For example, if a gene change occurs in a prolactin-secreting cell and causes that prolactin-secreting cell to divide excessively, a prolactinoma may form.

In most cases, gene changes need to occur in both copies of the gene in order for tumor formation to begin. This is known as a recessive gene change. However, occasionally a change in only one copy of the gene will result in a tumor. This type of gene change is known as dominant.


Are Pituitary Adenomas Hereditary?
In order for an individual to inherit a disorder from his or her parents, the gene change needs to have occurred in a reproductive cell (the sperm or the egg). If a gene change that leads to the formation of a pituitary tumor occurs in a pituitary cell, that change will not be passed on to his or her children.

There are several syndromes which are inherited (the gene change is in the reproductive cells) that can include pituitary tumors as part of the diagnosis. Multiple endocrine neoplasia type 1. Abbreviated MEN-1, a condition involving tumors of the pituitary gland, parathyroid gland, and the pancreas, is a familial syndrome. Nearly half of all individuals diagnosed with MEN-1 will develop a pituitary adenoma, most of which are Prolactinoma's. MEN-1 is considered a dominant disorder since a change in only one copy of the MEN-1 gene will cause the disease. Because of this, an individual diagnosed with MEN-1 will have a 50% chance of passing the altered gene on to his or her children. Those children that do get the altered MEN-1 gene will have roughly a 50% chance of developing a pituitary tumor as a part of MEN-1. Individuals with Carney Complex, which is another dominant disorder, can also develop pituitary adenomas. Approximately 20% of Carney Complex patients will develop growth hormone-secreting tumors.

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