The pituitary gland is termed the “master gland” as it plays a key role in controlling the production of hormones from other organs such as thyroid hormone, cortisol, estrogens, and testosterone. It also produces its own hormones including prolactin and antidiuretic hormone. Tumors arising from the pituitary gland itself are called adenomas, cysts, or carcinomas. Pituitary adenomas are almost always (>99%) benign (non-cancerous), slow-growing masses. Some benign pituitary adenomas demonstrate more aggressive behavior and tend to recur or grow more aggressively. Pituitary carcinoma is a rare malignant form of pituitary adenoma. It is diagnosed only when there is proven spread (metastases) inside or outside the nervous system. The most common cyst found in the pituitary gland is a Rathke’s cleft cyst, which is also benign (non-cancerous). There is a long list of other tumors that arise in this area, but these are rare.
Of note, small pituitary tumors are extremely common and are present in up to 10% of the population. Most of these will never grow and do not cause any symptoms. Many are found incidentally during a routine MRI and rarely require any treatment.
All pituitary adenomas arise from the front two-thirds of the pituitary gland, known as the anterior pituitary gland. These tumors are classified based on their size. Tumors less than 10 mm in diameter are termed microadenomas, and tumors greater than 10 mm in diameter are termed macroadenomas. Microadenomas are less likely to continue to grow over time, while macroadenomas typically get larger. Pituitary tumors are further classified as “secreting” and “non-secreting.” A “secreting” tumor produces excessive amounts of hormones and is most common. They are further classified by the type(s) of hormone(s) they produce. Non-secreting tumors cause a slowdown or a stoppage in hormone production (a condition called hypopituitarism). Despite hormone secreting tumors being the most common as a total group, non-secreting tumors are the most commonly operated on tumors.
Symptoms from pituitary tumors and cysts are generally caused either by pressure on the gland and surrounding structures or by excess hormone production, depending on the tumor type and size. When tumors get large, they can push on the pituitary gland itself causing it to stop producing hormones, leading to symptoms including headache, visual loss, hair loss, diminished libido, weight fluctuations, skin changes, and fatigue (lack of energy).
Since almost 70% of pituitary tumors are secreting, the most common symptoms are related to excess hormone production. The hormones most commonly affected include:
Pituitary tumors can cause a condition called hyperthyroidism. Symptoms of hyperthyroidism include weight loss, changes in heart rhythm, anxiety, changes in bowel patterns, fatigue, thinning skin, and difficulty sleeping. Excess growth hormone secretion can lead to a condition known as acromegaly, or gigantism when experienced in children. Excess cortisol production causes Cushing’s disease, a condition caused by excess production of a hormone called gluticosteroids. Symptoms of Cushing’s disease include developing a moon-shaped face, excess hair growth on the body, bruising, menstrual irregularities, and high blood pressure.
If the tumor pushes on the optic nerves that sit above the pituitary gland area it can cause loss of vision and headaches. Other less common symptoms include double vision, sinus congestion, and change in behavior.
Treatment of a pituitary tumor depends on the hormonal activity, its size and location, and the age and overall health of the individual. The goals of treatment may be to remove the tumor, reduce or control tumor size, and/or to re-balance hormone levels. Because the pituitary gland impacts so many of the body’s functions, a multi-disciplinary approach to tumor treatment is needed to ensure the best possible outcome.
A “watch and wait” approach can be used for many small tumors because their growth potential is low, especially if they are not causing any symptoms. For larger tumors causing pressure on the surrounding brain structure or pituitary gland, surgery is commonly performed. Most of these surgeries are done through the nose (transsphenoidal surgery) and can be carried out very safely. During transsphenoidal surgery, extremely small instruments, microscopes, and endoscopes are used to remove the tumor from within the nose or under the lip and above the teeth. In some cases, however, drug therapy may be used to reduce the size of the tumor, either without surgery or in addition to surgery. This is especially true for tumors that secrete prolactin and some that produce growth hormones.
Radiation therapy or stereotactic radiosurgery are sometimes used as additional treatments for pituitary tumors. They may be given in place of surgery or in addition to surgery and/or drug therapy. Radiation therapy may be used to treat aggressive tumors or those that have recurred. The goal of radiation therapy for pituitary tumors is to reduce or control tumor size.
Replacement hormone therapy is often prescribed following surgery and/or radiation.
Treatment requires input from surgeons and endocrinologists. It is critical that patients be given the correct diagnosis, which often requires a combination of MRI, blood tests, and visual field assessments. Patients also need to be aware of the many treatment options, and related benefits versus side effects.
Prognosis means a prediction of outcome. This information is usually based on information gathered from groups of people with the same disease. It is important to remember these statistics are not individualized.
The prognosis for most pituitary tumors is excellent. With surgery or medical therapy, most of these tumors can be cured or kept from growing for decades. Pituitary tumors almost always remain benign (non-cancerous), with less than 0.1% becoming truly cancerous. Surgery and medication can also be very effective in reversing deficits caused by the tumor, especially visual and hormonal symptoms. Cure rates from surgery range from 50-100% depending on tumor size, type, and location. For patients requiring medication, anywhere from 40-90% of tumors will remain stable after treatment.
About 13,770 pituitary tumors are diagnosed annually in the U.S., accounting for about 17% of all primary tumors in the central nervous system (CNS). Symptomatic pituitary tumors account for 9% to 12% of all primary brain tumors. Women are more affected than men, particularly during the childbearing years. The incidence rate of pituitary tumors is higher in African Americans and Hispanics than Caucasians. Pituitary carcinomas occur in less than 1 in 10,000 tumors.
It is estimated that approximately 10% of the population has a pituitary tumor, however, most of these are undetected because the tumors are small and do not cause any symptoms. These tumors have no growth potential and do not require any treatment. Because incidentally discovered pituitary tumors are so common, routine screening is not indicated, and a conservative approach is best for most people.
Pituitary tumors can occur in all age groups but tend to be detected most commonly in 50–75-year-olds. This is likely due to the very slow growth pattern in these tumors, often taking decades before causing symptoms leading to detection. Pituitary tumors rarely occur in children, but are the most common primary brain tumor diagnosed in adolescents age 15-19.
No clear risk factors have been identified for developing pituitary tumors, other than a few genetic syndromes. Multiple Endocrine Neoplasia I (MEN-1) is the most common genetic syndrome, and 30-40% of people with this syndrome will develop pituitary tumors. Other syndromes include Carney Complex, Familial Isolated Pituitary Adenoma (FIPA), Dicer Syndrome, and X-linked Acrogigantism. These syndromes are rare, representing less than 5% of all tumors. Patients with no family history of tumors are generally not screened for these syndromes.
Molecular profiling is the detection of specific genes, proteins, or other molecules in a tumor. This information helps confirm tumor diagnosis, inform treatment options, and predict prognosis.
Sporadically occurring pituitary tumors, representing over 95% of tumors, appear to carry only two main mutations in the GNAS and USP8 genes. Cells that arise from prolactin, growth hormone, or thyroid stimulating hormone linage are under the regulation of the Pit-1 gene, while those secreting ACTH are regulated by t-pit. Cells that produce LH and FSH are regulated by SF-1. It is not clear what the primary drivers are that lead to mutations in pituitary cells to cause tumors, but these appear to be mono-clonal, meaning they occur only in one cell type or line per tumor.
July 2022 by Adam N. Mamelak, MD
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