Key Terms: Adenoma, Agonist, Benign, Carney complex, Dopamine, Hormone, Invasive, McCune-Albright syndrome, Multiple endocrine neoplasia syndrome type I.
Definition
Pituitary tumors are abnormal growths in the pituitary gland.
Description
Located in the brain, the pituitary gland is often referred to as the "master gland" of the body. This is because it makes and releases (secretes) at least nine distinct hormones (including oxytocin, antidiuretic hormone [ADH], prolactin, thyroid-stimulating hormone [TSH], adrenocorticotropic hormone [ACTH], follicle-stimulating hormone [FSH], luteinizing hormone [LH], and human growth hormone [HGH]) that regulate the activities of several other endocrine glands and influence a number of physiological processes including growth, sexual development and functioning, and the fluid balance of the body. The pituitary is divided into two parts: front (anterior) and rear (posterior). Each half of the pituitary gland secretes specific hormones. Tumors in the anterior part are common and are usually noncancerous (benign). Tumors rarely develop in the posterior portion. Between 10% and 15% of all tumors in the skull are pituitary tumors, which makes them the third most common type of brain tumor.
Virtually all pituitary tumors arise from a single cell which, for unknown reasons, has grown out of control. Tumors that have originated from a single cell are called monoclonal. Some tumors secrete hormones normally made by the pituitary gland. Because the tumor cells are uncontrolled, they secrete large amounts of hormones. As a result, hormone imbalance occurs. The symptoms caused by the hormone imbalance are often the first sign of a pituitary tumor.
There are several different types of pituitary tumors. Pituitary adenomas (adenomas are tumors that grow from gland tissues) are the most common type. Most pituitary adenomas are benign, although they may spread to nearby tissues. Pituitary adenomas can be further classified based on which, if any, hormones are secreted by the tumor. Thirty-five percent of pituitary adenomas do not secrete hormones, 27% secrete prolactin (prolactinomas), and 21% secrete growth hormone. The remaining pituitary adenomas secrete sex hormones (6%), thyroid hormones (1%), or adrenal (adrenocorticotropic) hormones (8%). Plurihormonal adenomas secrete more than one type of hormone. Tumors that secrete adrenocorticotropic hormone cause Cushing's syndrome and Nelson's syndrome.
Craniopharyngiomas are benign tumors that originate in tissues next to the pituitary gland. Technically speaking, they are not pituitary tumors although they affect the pituitary gland. They are extremely difficult to remove and radiation does not stop craniopharyngiomas from spreading throughout the pituitary gland. Craniopharyngiomas account for less than 5% of all brain tumors.
Pituitary carcinoma is a very rare condition. Fewer than 100 cases have ever been reported. It is usually diagnosed when a pituitary tumor, which was believed to be an adenoma, spreads (metastasizes) to distant organs. These pituitary tumors may or may not release hormones. Because pituitary carcinoma is often diagnosed late, it has a high death rate.
Demographics
Pituitary tumors occur more frequently in women than in men. They usually develop between the ages of 30 and 40. Half of all craniopharyngiomas occur in children, with symptoms most often appearing between the ages of five and ten.
Causes and Symptoms
The cause of pituitary tumors is not known. Most pituitary tumors presumably result from changes to the DNA of one cell, leading to uncontrolled cell growth. The genetic defects, multiple endocrine neoplasia syndrome type I (MEN I or Wermer's syndrome), McCune-Albright syndrome, and the Carney complex, are associated with pituitary tumors. However, these defects account for only a small percentage of the cases of pituitary tumors. Also, a pituitary tumor may result from the spread (metastasis) of cancer from another site. Breast cancer in women and lung cancer in men are the most common cancers to spread to the pituitary gland. Other cancers that spread to the pituitary gland include kidney cancer, prostate cancer, melanoma, and gastrointestinal cancers.
Symptoms related to tumor location, size, and pressure on neighboring structures include:
- persistent headache on one or both sides, or in the center of the forehead
- blurred or double vision; loss of side (peripheral) vision
- drooping eyelid (ptosis) caused by pressure on nerves leading to the eye
- numb feeling on the face
- dementia
- drowsiness
- enlarged head
- eating excessive (hyperphagia) or abnormally small (hypophagia) amounts of food
- seizures
The specific symptoms associated with hormone-secreting tumors will vary depending on which hormones are being over-produced. Symptoms related to hormonal imbalance include:
- excessive sweating
- loss of appetite
- loss of interest in sex
- inability to tolerate cold temperatures
- nausea
- menstrual problems
- excessive thirst
- frequent urination
- dry skin
- constipation
- premature or delayed puberty
- delayed growth in children
- milk secretion in the absence of pregnancy or breast feeding (galactorrhea)
- reduced strength
- mood alterations (depression, anxiety, unstable emotions)
- muscle pain
- low blood sugar (sudden occurrence of shakiness and sweating)
Patients who have sudden pituitary failure caused by bleeding or tissue death (pituitary apoplexy also known as Sheehan's syndrome) may experience very severe headaches, confusion, loss of sight, and drowsiness. This condition is considered an emergency.
Tumors that secrete growth hormone cause a condition called acromegaly. This long-term condition is characterized by enlargement of the nose, ears, jaws, toes, and fingers. Joint pain, blood sugar imbalances, high blood pressure, carpal tunnel syndrome, and airway blockages can result.
Diagnosis
As many as 40% of all pituitary tumors do not release excessive quantities of hormones into the blood. Known as clinically nonfunctioning, these tumors are difficult to distinguish from tumors that produce similar symptoms. They may grow to be quite large before they are diagnosed.
The diagnosis of pituitary tumors is based on:
- the patient's own observations and medical history
- physical examination
- laboratory studies of the patient's blood and brain/spinal fluid (cerebrospinal fluid)
- x rays of the skull and other studies that provide images of the inside of the brain (CT, MRI)
- vision tests
- urinalysis
Treatment Team
The treatment team for pituitary tumors may include a neuroendocrinologist, endocrinologist, neurosurgeon, oncologist, radiation oncologist, nurse oncologist, psychiatrist, psychological counselor, and social worker.
Clinical Staging, Treatments, and Prognosis
Clinical Staging
Because most pituitary tumors are benign, there is no clinical staging system.
Treatments
Treatment is determined by the type of tumor, the type of hormone being released, and whether or not the tumor has invaded tissues next to the pituitary gland. The goals of treatment are to normalize hormone levels and reduce the size of (or remove) the tumor. Treatment options include surgery, radiation, and/or medication. Some pituitary tumors stabilize without treatment. Small tumors that are not causing significant symptoms may be watched only.
Surgery is usually used to remove all or part of a tumor within the gland or the area surrounding it. Surgery may be combined with radiation therapy to treat tumors that extend beyond the pituitary gland. A neurosurgeon will operate immediately to remove the tumor or pituitary gland (hypophysectomy) of a patient whose vision is deteriorating rapidly. Approximately 96% of the surgeries are performed through the nose (transsphenoidal). If the tumor is large, the skull may be opened (craniotomy) for tumor removal. Removal or destruction of the pituitary gland requires life-long hormone replacement therapy. The most common complications of surgery are leakage of cerebrospinal fluid through the nose and inflammation of the membranes that surround the brain and spinal column (meningitis).
Radiation therapy is not as effective as surgery and is usually reserved for tumors that have not responded to other treatments and those that recur. Radioactive pellets can be implanted in the brain to treat the tumor. Selected patients are treated with proton beam radiosurgery that uses high energy particles in the form of a high energy beam to destroy an overactive pituitary gland. Fatigue, upset stomach, diarrhea, and nausea are common complaints of patients having radiation therapy. Radiation therapy to the brain can damage certain brain tissues.
Dopamine agonists, drugs that increase the effect of the brain chemical dopamine, are effective in treating tumors that release hormones. These drugs can reduce symptoms caused by a pituitary tumor and reduce the size of the tumor. Commonly used dopamine agonists include bromocriptine, pergolide, and cabergoline. Cabergoline is the most effective and produces fewer side effects than the other two drugs. Side effects associated with dopamine agonists include nausea, vomiting, and light-headedness when rising (postural hypotension). Acromegaly may be treated with somatostatin and other drugs derived from somatostatin (analogues). Tumors, and the symptoms they are causing, return when drug use is stopped. Patients should wear medical identification tags identifying their condition and the hormonal replacement medicines they take.
The common treatments for specific pituitary tumors are:
- Prolactin-secreting adenoma. Prolactinomas are treated with a dopamine agonist. Surgical treatment is used if the drug fails or causes intolerable side effects.
- Gonadotropin-secreting adenoma. Small tumors are not treated unless they are causing symptoms. Large tumors and small tumors that are causing symptoms are treated surgically. Radiation therapy may be used.
- Adrenocorticotropic hormone-secreting adenoma. Surgery is the treatment of choice. Medications that prevent adrenal hormone production or radiation therapy may be used if surgery fails.
- Growth hormone-secreting adenoma. Surgery is the treatment of choice. Medications (dopamine agonists, somatostatins) or radiation therapy may be used.
- Thyroid stimulating hormone-secreting adenoma. Surgery, with or without radiation therapy, is the treatment of choice. Although somatostatin treatment may reduce hormone levels, it fails to shrink the tumor.
- Nonsecreting adenoma. Surgery is the treatment of choice. In general, medications are not effective for this type of tumor. Radiation therapy may be used to prevent tumor recurrence.
- Pituitary carcinoma. Carcinoma is treated with standard cancer radiation therapy and chemotherapy.
- Craniopharyngiomas. These tumors are difficult to treat. Due to the nature of craniopharyngiomas, surgery is often incomplete and needs to be complemented by radiation therapy.
Prognosis
Pituitary tumors are usually curable. Pituitary adenomas that secrete adrenocorticotropic hormone are frequently persistent and have a high rate of recurrence. Approximately 5% of pituitary adenomas invade nearby tissues and grow to large sizes, making them more difficult to treat and subject to frequent recurrences. Metastasis of most pituitary tumors is very rare. However, pituitary carcinomas can metastasize and are associated with a poor prognosis.
Alternative and Complementary Therapies
Alternative and complementary therapies have not been shown to be effective in treating pituitary tumors. For more comprehensive information, the patient should consult the book on complementary and alternative medicine published by the American Cancer Society listed in the Resources section.
Coping With Cancer Treatment
The patient should consult his or her treatment team regarding any side effects or complications of treatment. Patients may want to consult a psychotherapist and/or join a support group to deal with the emotional consequences of cancer and its treatment.
Clinical Trials
There are two active clinical trials studying pituitary tumors are studying the safety and effectiveness of antineoplastons. Study #BRI-BT-9 is open to patients with serious or life-threatening brain tumors. Study #BRI-NE-2 is open to patients who have metastatic or incurable neuroendocrine tumors. The National Cancer Institute web site has information on these and other studies. Patients should consult with their treatment teams to determine if they are candidates for these or any other ongoing studies.
Questions to Ask the Doctor
- Is my tumor cancerous? Is it invasive?
- What are my treatment options?
- What are the risks and side effects of these treatments?
- Is surgery really necessary?
- Which surgical approach will you use?
- How experienced are you at performing pituitary surgery?
- How will I feel immediately following surgery?
- Will I need to take medication for the rest of my life?
- How long will it take for my symptoms to go away?
- Will I be able to have children?
- Is it safe to become pregnant while taking this medication?
- How will pregnancy affect my tumor?
- What medications can I take to relieve treatment side effects?
- Are there any clinical studies underway that would be appropriate for me?
- What is the chance that the tumor will recur?
- How will recurrence be detected?
- How often will I have follow-up examinations?
Special Concerns
Long-term low levels of sex hormones (hypogonadism) can have negative effects on bone density and the cardiovascular system. The effect a pituitary tumor has on fertility is a concern for both men and women. Women taking medications to treat pituitary tumors need to question their physicians regarding the potential effect the medications may have on an unborn baby.
Resources
Books
Bruss, Katherine, Christina Salter, and Esmeralda Galan, editors. American Cancer Society's Guide to Complementary and Alternative Cancer Methods. Atlanta: American Cancer Society, 2000.
DeAngelis, Lisa, and Jerome Posner. "Cancer of the Central Nervous System and Pituitary Gland." In Clinical Oncology, edited by Raymond Lenhard, Robert Osteen, and Ted Gansler. Atlanta: American Cancer Society, 2004, pp.653–703.
Krisht, Ali, and George Tindall, editors. Pituitary Disorders: Comprehensive Management. Baltimore: Lippincott Williams & Wilkins, 1999.
Molitch, Mark, editor. Endocrinology and Metabolism Clinics of North America: Advances in Pituitary Tumor Therapy. Philadelphia: W.B. Saunders Company, 1999.
Periodicals
Wardlaw, Fred, P. Wardlaw, and S. Wardlaw. "Diagnosis and Treatment of Pituitary Tumors." The Journal of Clinical Endocrinology & Metabolism 84 (November 1999): 3859-66.
Organizations
American Brain Tumor Association. 2770 River Road, Des Plaines, IL 60018. (800) 886-2289. .
American Cancer Society. 1599 Clifton Road NE, Atlanta, GA 30329. (800) ACS-2345. .
Brain Tumor Information Services. Box 405, Room J341, University of Chicago Hospitals, 5841 S. Maryland Avenue, Chicago, IL 60637. (312) 684-1400.
Cancer Research Institute, National Headquarters. 681 Fifth Ave., New York, NY 10022. (800) 992-2623. .
National Institutes of Health. National Cancer Institute. 9000 Rockville Pike, Bethesda, MD 20982. Cancer Information Service: (800) 4-CANCER. .
—Maureen Haggerty; Belinda Rowland, Ph.D.
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