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Home , Prolactinoma

Prolactinoma

National Endocrine and Metabolic Diseases Information Service

What is a prolactinoma? A prolactinoma is a benign—noncancerous— tumor of the pituitary that produces a called . Prolactinomas are U.S. Department of Health and the most common type of pituitary tumor. Human Services Symptoms of prolactinoma are caused by hyperprolactinemia—too much prolactin in NATIONAL the blood—or by pressure of the tumor on INSTITUTES OF HEALTH surrounding tissues. Prolactin stimulates the to produce milk during pregnancy. After giving birth, Sella a mother’s prolactin levels fall unless she turcica breastfeeds her infant. Each time the baby nurses, prolactin levels rise to maintain milk production. Pituitary What is the ? The pituitary gland, sometimes called the master gland, plays a critical role in regulat­ ing growth and development, metabolism, and reproduction. It produces prolactin and other key including The pituitary gland sits in the sella turcica. • growth hormone, which regulates growth • luteinizing hormone and follicle- stimulating hormone, which regulate • adrenocorticotropin (ACTH), which ovulation and and progester­ stimulates the adrenal to pro­ one production in women and sperm duce cortisol, a hormone important in formation and production metabolism and the body’s response to in men stress The pituitary gland sits in the middle of the • thyrotropin, which signals the head in a bony box called the sella turcica. gland to produce thyroid hormone, also The optic nerves sit directly above the pitu­ involved in metabolism and growth itary gland. Enlargement of the gland can cause symptoms such as headaches or visual What causes prolactinoma? disturbances. Pituitary tumors may also The cause of pituitary tumors remains impair production of one or more pituitary largely unknown. Most pituitary tumors are hormones, causing reduced pituitary func­ sporadic, meaning they are not genetically tion, also called . passed from parents to their children.

How common is What else causes prolactin prolactinoma? to rise? Although small benign pituitary tumors are In some people, high blood levels of pro­ fairly common in the general population, lactin can be traced to causes other than symptomatic prolactinomas are uncommon. prolactinoma. Prolactinomas occur more often in women than men and rarely occur in children. Prescription drugs. Prolactin secretion in the pituitary is normally suppressed by the What are the symptoms of brain chemical . Drugs that block the effects of dopamine at the pituitary or prolactinoma? deplete dopamine stores in the brain may In women, high levels of prolactin in the cause the pituitary to secrete prolactin. blood often cause and changes in These drugs include older antipsychotic . In some women, periods may medications such as trifluoperazine (Stela­ stop. In others, periods may become irregu­ zine) and haloperidol (Haldol); the newer lar or menstrual flow may change. Women antipsychotic drugs risperidone (Risperdal) who are not pregnant or nursing may begin and molindone (Moban); metoclopramide producing . Some women may (Reglan), used to treat gastroesophageal experience a loss of libido—interest in sex. reflux and the caused by certain Intercourse may become painful because of drugs; and less often, verapamil, vaginal dryness. alpha–methyldopa (Aldochlor, Aldoril), and reserpine (Serpalan, Serpasil), used to In men, the most common symptom of pro­ control high blood pressure. Some antide­ lactinoma is . Because pressants may cause hyperprolactinemia, but men have no reliable indicator such as further research is needed. changes in menstruation to signal a problem, many men delay going to the doctor until Other pituitary tumors. Other tumors they have headaches or eye problems caused arising in or near the pituitary may block by the enlarged pituitary pressing against the flow of dopamine from the brain to nearby optic nerves. They may not recognize the prolactin-secreting cells. Such tumors a gradual loss of sexual function or libido. include those that cause , a condi­ Only after treatment do some men realize tion caused by too much growth hormone, they had a problem with sexual function. and Cushing’s syndrome, caused by too much cortisol. Other pituitary tumors that do not result in excess hormone production may also block the flow of dopamine.

2 Prolactinoma Hypothyroidism. Increased prolactin levels How is prolactinoma are often seen in people with hypothyroid­ ism, a condition in which the thyroid does treated? not produce enough thyroid hormone. The goals of treatment are to return prolac­ Doctors routinely test people with hyperpro­ tin secretion to normal, reduce tumor size, lactinemia for hypothyroidism. correct any visual abnormalities, and restore normal pituitary function. In the case of Chest involvement. Nipple stimulation also large tumors, only partial achievement of can cause a modest increase in the amount of these goals may be possible. prolactin in the blood. Similarly, chest wall injury or shingles involving the chest wall Medical Treatment may also cause hyperprolactinemia. Because dopamine is the chemical that normally inhibits prolactin secretion, doc­ How is prolactinoma tors may treat prolactinoma with the dop­ diagnosed? amine agonists (Parlodel) or (Dostinex). Agonists are drugs A doctor will test for prolactin blood levels that act like a naturally occurring substance. in women with unexplained milk secretion, These drugs shrink the tumor and return called , or with irregular menses prolactin levels to normal in approximately or infertility and in men with impaired sexual 80 percent of patients. Both drugs have function and, in rare cases, milk secretion. been approved by the U.S. Food and Drug If prolactin levels are high, a doctor will test Administration for the treatment of hyper­ thyroid function and ask first about other prolactinemia. Bromocriptine is the only conditions and medications known to raise approved for the treat­ prolactin secretion. The doctor may also ment of infertility. This drug has been in request magnetic resonance imaging (MRI), use longer than cabergoline and has a well- which is the most sensitive test for detecting established safety record. pituitary tumors and determining their size. MRI scans may be repeated periodically to Nausea and are possible side assess tumor progression and the effects of effects of bromocriptine. To avoid these therapy. Computerized tomography (CT) side effects, bromocriptine treatment must scan also gives an image of the pituitary but be started slowly. A typical starting dose is is less precise than the MRI. one-quarter to one-half of a 2.5 milligram (mg) tablet taken at bedtime with a snack. The doctor will also look for damage to The dose is gradually increased every 3 to surrounding tissues and perform tests to 7 days as needed and taken in divided doses assess whether production of other pituitary with meals or at bedtime with a snack. Most hormones is normal. Depending on the size people are successfully treated with 7.5 mg of the tumor, the doctor may request an eye a day or less, although some people need exam with measurement of visual fields. 15 mg or more each day. Because bro­ mocriptine is short acting, it should be taken either twice or three times daily.

3 Prolactinoma Bromocriptine treatment should not be those used for prolactinomas, heart valve stopped without consulting a qualified damage has been reported. Rare cases endocrinologist—a doctor specializing in of valve damage have been reported in disorders of the hormone-producing glands. people taking low doses of cabergoline to Prolactin levels rise again in most people treat hyperprolactinemia. Before starting when the drug is discontinued. In some, these medications, the doctor will order an however, prolactin levels remain normal, so echocardiogram. An echocardiogram is a the doctor may suggest reducing or discon­ sonogram of the heart that checks the heart tinuing treatment every 2 years on a trial valves and heart function. basis. Because limited information exists about Cabergoline is a newer drug that may be the risks of long-term, low-dose cabergoline more effective than bromocriptine in nor­ use, doctors generally prescribe the lowest malizing prolactin levels and shrinking tumor effective dose and periodically reassess the size. Cabergoline also has less frequent and need for continuing therapy. People taking less severe side effects. Cabergoline is more cabergoline who develop symptoms of short­ expensive than bromocriptine and, being ness of breath or swelling of the feet should newer on the market, its long-term safety promptly notify their physician because these record is less well defined. As with bro­ may be signs of heart valve damage. mocriptine therapy, nausea and dizziness are possible side effects but may be avoided if Surgery treatment is started slowly. The usual start­ Surgery to remove all or part of the tumor ing dose is .25 mg twice a week. The dose should only be considered if medical therapy may be increased every 4 weeks as needed, cannot be tolerated or if it fails to reduce up to 1 mg two times a week. Cabergoline prolactin levels, restore normal reproduction should not be stopped without consulting a and pituitary function, and reduce tumor qualified endocrinologist. size. If medical therapy is only partially successful, it should be continued, possibly Recent studies suggest prolactin levels are combined with surgery or radiation. more likely to remain normal after discon­ tinuing long-term cabergoline therapy than Most often, the tumor is removed through after discontinuing bromocriptine. More the nasal cavity. Rarely, if the tumor is large research is needed to confirm these findings. or has spread to nearby brain tissue, the surgeon will access the tumor through an In people taking cabergoline or bro­ opening in the skull. mocriptine to treat Parkinson’s disease at doses more than 10 times higher than

4 Prolactinoma The results of surgery depend a great deal How does prolactinoma on tumor size and prolactin levels as well as the skill and experience of the neurosurgeon. affect pregnancy? The higher the prolactin level before surgery, If a woman has a small prolactinoma, she the lower the chance of normalizing serum can usually conceive and have a normal prolactin. Serum is the portion of the blood pregnancy after effective medical therapy. If used in measuring prolactin levels. In the she had a successful pregnancy before, the best medical centers, surgery corrects pro­ chance of her having more successful preg­ lactin levels in about 80 percent of patients nancies is high. with small tumors and a serum prolactin less A woman with prolactinoma should discuss than 200 nanograms per milliliter (ng/ml). her plans to conceive with her physician A surgical cure for large tumors is lower, at so she can be carefully evaluated prior to 30 to 40 percent. Even in patients with large becoming pregnant. This evaluation will tumors that cannot be completely removed, include an MRI scan to assess the size of the drug therapy may be able to return serum tumor and an eye examination with measure­ prolactin to the normal range—20 ng/ml or ment of visual fields. As soon as a woman is less—after surgery. Depending on the size pregnant, her doctor will usually advise her of the tumor and how much of it is removed, to stop taking bromocriptine or cabergoline. studies show that 20 to 50 percent will recur, Although these drugs are safe for the fetus in usually within 5 years. early pregnancy, their safety throughout an Because the results of surgery are so depen­ entire pregnancy has not been established. dent on the skill and knowledge of the neu­ Many doctors prefer to use bromocriptine rosurgeon, a patient should ask the surgeon in patients who plan to become pregnant about the number of operations he or she because it has a longer record of safety in has performed to remove pituitary tumors early pregnancy than cabergoline. and for success and complication rates in The pituitary enlarges and prolactin produc­ comparison to major medical centers. The tion increases during pregnancy in women best results come from surgeons who have without pituitary disorders. Women with performed hundreds or even thousands of prolactin-secreting tumors may experience such operations. To find a surgeon, con­ further pituitary enlargement and must be tact The Pituitary Society (see For More closely monitored during pregnancy. Less Information). than 3 percent of pregnant women with small Radiation prolactinomas have symptoms of tumor growth such as headaches or vision problems. Rarely, radiation therapy is used if medical In women with large prolactinomas, the risk therapy and surgery fail to reduce prolactin of symptomatic tumor growth is greater, and levels. Depending on the size and location of may be as high as 30 percent. the tumor, radiation is delivered in low doses over the course of 5 to 6 weeks or in a single high dose. Radiation therapy is effective about 30 percent of the time.

5 Prolactinoma Most endocrinologists see patients every Is osteoporosis a risk in 2 months throughout the pregnancy. A woman should consult her endocrinologist women with high prolactin promptly if she develops symptoms of tumor levels? growth—particularly headaches, vision Women whose ovaries produce inadequate changes, nausea, vomiting, excessive thirst or estrogen are at increased risk for osteoporo­ urination, or extreme lethargy. Bromocrip­ sis. Hyperprolactinemia can reduce estrogen tine or, less often, cabergoline treatment may production. Although estrogen production be reinitiated and additional treatment may may be restored after treatment for hyper­ be required if the woman develops symptoms prolactinemia, even a year or 2 without during pregnancy. estrogen can compromise bone strength. Women should protect themselves from How do oral contraceptives osteoporosis by increasing exercise and calcium intake through diet or supplements and hormone replacement and by not smoking. Women treated for therapy affect prolactinoma? hyperprolactinemia may want to have peri­ Oral contraceptives are not thought to con­ odic bone density measurements and discuss tribute to the development of prolactinomas, estrogen replacement therapy or other bone- although some studies have found increased strengthening medications with their doctor. prolactin levels in women taking these medications. Because oral contraceptives may produce regular menstrual bleeding in women who would otherwise have irregular menses due to hyperprolactinemia, prolac­ tinoma may not be diagnosed until women stop oral contraceptives and find their menses are absent or irregular. Women with prolactinoma treated with bromocriptine or cabergoline may safely take oral contracep­ tives. Similarly, postmenopausal women treated with medical therapy or surgery for prolactinoma may be candidates for estrogen replacement therapy.

6 Prolactinoma Hope through Research Points to Remember Researchers are working to identify a gene • A prolactinoma is a or genes that may contribute to the develop­ of the pituitary gland that produces ment of pituitary tumors, including sporadic the hormone prolactin. Prolactin tumors. They are also investigating certain stimulates the breast to produce side effects of long-term treatment for pro­ milk during pregnancy. lactinomas with cabergoline. • In women, high levels of prolactin Participants in clinical trials can play a more in the blood often cause infertil­ active role in their own health care, gain ity and changes in menstruation. access to new research treatments before Women who are not pregnant or they are widely available, and help others by nursing may begin producing breast contributing to medical research. For infor­ milk. In men, the most common mation about current studies, visit symptom of prolactinoma is erec­ www.ClinicalTrials.gov. tile dysfunction. • Prolactinoma is diagnosed through For More Information a blood test. Additional tests rule American Association of Clinical out other causes of high prolac­ Endocrinologists tin levels, such as medications 245 Riverside Avenue, Suite 200 or thyroid problems. Magnetic Jacksonville, FL 32202 resonance imaging (MRI) is then Phone: 904–353–7878 used to detect pituitary tumors and Fax: 904–353–8185 determine their size. Internet: www.aace.com • The first line of treatment is usually The Endocrine Society medication to shrink the tumor and 8401 Connecticut Avenue, Suite 900 return prolactin levels to normal. Chevy Chase, MD 20815–5817 Sometimes surgery or radiation Phone: 1–888–363–6274 or 301–941–0200 may be necessary. Fax: 301–941–0259 • Women with prolactinoma Internet: www.endo-society.org should be carefully evaluated The Pituitary Society before becoming pregnant and VA Medical Center monitored during pregnancy by an 423 East 23rd Street, Room 16048aW endocrinologist. New York, NY 10010 Phone: 212–263–6772 Fax: 212–447–6219 Internet: www.pituitarysociety.org

7 Prolactinoma Acknowledgments National Endocrine Publications produced by the NIDDK are and Metabolic Diseases carefully reviewed by both NIDDK scien- Information Service tists and outside experts. This publication was reviewed by Michael O. Thorner, M.B., 6 Information Way D.Sc., University of Virginia Health System, Bethesda, MD 20892–3569 and Shlomo Melmed, M.D., Cedars-Sinai Phone: 1–888–828–0904 Health System. TTY: 1–866–569–1162 Fax: 703–738–4929 Email: [email protected] Internet: www.endocrine.niddk.nih.gov You may also find additional information about this topic by visiting MedlinePlus at www..gov. The National Endocrine and Metabolic Dis- This publication may contain information about eases Information Service is an information medications. When prepared, this publication included the most current information available. dissemination service of the National Insti- For updates or for questions about any medications, tute of Diabetes and Digestive and Kidney contact the U.S. Food and Drug Administration toll-free at 1–888–INFO–FDA (1–888–463–6332) Diseases (NIDDK). The NIDDK is part of or visit www.fda.gov. Consult your doctor for more the National Institutes of Health, which is information. part of the U.S. Department of Health and Human Services. The NIDDK conducts and supports bio- The U.S. Government does not endorse or favor any medical research. As a public service, the specific commercial product or company. Trade, proprietary, or company names appearing in this NIDDK has established information services document are used only because they are considered to increase knowledge and understanding necessary in the context of the information provided. about health and disease among patients, If a product is not mentioned, the omission does not mean or imply that the product is unsatisfactory. health professionals, and the public.

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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health

NIH Publication No. 09–3924 May 2009