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What Is a Prolactinoma?
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A prolactinoma is a benign tumor of the
pituitary gland that produces a hormone called prolactin. It is the most
common type of pituitary tumor. Symptoms of prolactinoma are caused by too
much prolactin in the blood (hyperprolactinemia) or by pressure of the
tumor on surrounding tissues.
Prolactin stimulates the breast to produce milk during pregnancy. After
delivery of the baby, a mother's prolactin levels fall unless she breast
feeds her infant. Each time the baby nurses, prolactin levels rise to
maintain milk production.
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What Is the Pituitary Gland?
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The pituitary gland, sometimes called the
master gland, plays a critical role in regulating growth and development,
metabolism, and reproduction. It produces prolactin and a variety of other
key hormones. These include growth hormone, which regulates growth; ACTH (corticotropin),
which stimulates the adrenal glands to produce cortisol; thyrotropin,
which signals the thyroid gland to produce thyroid hormone; and
luteinizing hormone and follicle-stimulating hormone, which regulate
ovulation and estrogen and progesterone production in women, and sperm
formation and testosterone production in men.
The pituitary gland sits in the middle of the head in a bony box called
the sella turcica. The eye nerves sit directly above the
pituitary gland. Enlargement of the gland can cause local symptoms such as
headaches or visual disturbances. Pituitary tumors may also impair
production of one or more pituitary hormones, causing reduced pituitary
function (hypopituitarism).
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How Common Is Prolactinoma?
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Autopsy studies indicate that 25 percent of
the U.S. population have small pituitary tumors. Forty percent of these
pituitary tumors produce prolactin, but most are not considered clinically
significant. Clinically significant pituitary tumors affect the health of
approximately 14 out of 100,000 people.
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What Causes Prolactinoma?
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Although research continues to unravel the
mysteries of disordered cell growth, the cause of pituitary tumors remains
unknown. Most pituitary tumors are sporadic--they are not genetically
passed from parents to offspring.
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What Are the Symptoms?
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In women, high blood levels of prolactin often
cause infertility and changes in menstruation. In some women, periods may
disappear altogether. In others, periods may become irregular or menstrual
flow may change. Women who are not pregnant or nursing may begin producing
breast milk. Some women may experience a loss of libido (interest in sex).
Intercourse may become painful because of vaginal dryness.
In men, the most common symptom of prolactinoma is impotence. Because
men have no reliable indicator such as menstruation to signal a problem,
many men delay going to the doctor until they have headaches or eye
problems caused by the enlarged pituitary pressing against nearby eye
nerves. They may not recognize a gradual loss of sexual function or
libido. Only after treatment do some men realize they had a problem with
sexual function.
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What Else Causes Prolactin To Rise?
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In some people, high blood levels of prolactin
can be traced to causes other than a pituitary tumor.
Prescription Drugs. Prolactin secretion in the
pituitary is normally suppressed by the brain chemical, dopamine. Drugs
that block the effects of dopamine at the pituitary or deplete dopamine
stores in the brain may cause the pituitary to secrete prolactin. These
drugs include the major tranquilizers trifluoperazine (Stelazine) and
haloperidol (Haldol); metoclopramide (Reglan), used to treat
gastroesophageal reflux and the nausea caused by certain cancer drugs; and
less often, alpha methyldopa and reserpine, used to control hypertension.
Other Pituitary Tumors. Other tumors arising in or
near the pituitary--such as those that cause acromegaly or Cushing's
syndrome--may block the flow of dopamine from the brain to the
prolactin-secreting cells.
Hypothyroidism. Increased prolactin levels are often
seen in people with hypothyroidism, and doctors routinely test people with
hyperprolactinemia for hypothyroidism.
Breast Stimulation also can cause a modest increase in
the amount of prolactin in the blood.
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How is Prolactinoma Diagnosed?
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A doctor will test for prolactin blood levels
in women with unexplained milk secretion (galactorrhea) or irregular
menses or infertility, and in men with impaired sexual function and, in
rare cases, milk secretion. If prolactin is high, a doctor will test
thyroid function and ask first about other conditions and medications
known to raise prolactin secretion. The doctor will also request a
magnetic resonance imaging (MRI), which is the most sensitive test for
detecting pituitary tumors and determining their size. MRI scans may be
repeated periodically to assess tumor progression and the effects of
therapy. Computer Tomography (CT scan) also gives an image of the
pituitary, but it is less sensitive than the MRI.
In addition to assessing the size of the pituitary tumor, doctors also
look for damage to surrounding tissues, and perform tests to assess
whether production of other pituitary hormones is normal. Depending on the
size of the tumor, the doctor may request an eye exam with measurement of
visual fields.
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How Is Prolactinoma Treated?
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Medical Treatment
The goal of treatment is to return prolactin secretion to normal, reduce
tumor size, correct any visual abnormalities, and restore normal pituitary
function. In the case of very large tumors, only partial achievement of
this goal may be possible. Because dopamine is the chemical that normally
inhibits prolactin secretion, doctors may treat prolactinoma with
bromocriptine or cabergoline, drugs that act like dopamine. This type of
drug is called a dopamine agonist. These drugs shrink the tumor and return
prolactin levels to normal in approximately 80 percent of patients. Both
have been approved by the Food and Drug Administration for the treatment
of hyperprolactinemia. Bromocriptine is the only dopamine agonist approved
for the treatment of infertility. Another dopamine agonist, pergolide, is
available in the U.S., but is not approved for treating conditions that
cause high blood levels of prolactin.
Bromocriptine is associated with side effects such as nausea and
dizziness. To avoid these side effects, it is important for bromocriptine
treatment to start slowly. An example of a typical approach used by an
experienced endocrinologist follows:
Begin by taking a quarter of a 2.5 milligram tablet of bromocriptine
with a snack at bedtime. After 3 days, increase the dose to a quarter of a
tablet with breakfast and a quarter at bedtime. After 3 more days, take
half a tablet twice a day, and 3 days later, one tablet at night and half
with breakfast. Finally, the dose is increased to one tablet twice a day.
If prolactin is still high, add half a tablet with lunch. If the
medication is well tolerated, increase the dose to a full tablet. If side
effects develop with a higher dose, return to the previous dosage. With
time, side effects disappear while the drug continues to lower prolactin.
Bromocriptine treatment should not be interrupted without consulting a
qualified endocrinologist. Prolactin levels often rise again in most
people when the drug is discontinued. In some, however, prolactin levels
remain normal, so the doctor may suggest reducing or discontinuing
treatment every two years on a trial basis.
Cabergoline is also associated with side effects such as nausea and
dizziness, but these may be less common and less severe than with
bromocriptine. As with bromocriptine therapy, side effects may be avoided
if treatment is started slowly. An example of a typical approach used by
an experienced endocrinologist follows:
Begin by taking .25 milligrams (or 1/2 tablet) twice a week. After four
weeks, increase the dose by .25 milligrams to .50 milligrams (or 1
tablet) twice a week. After four more weeks, increase the dose by .25
milligrams to .75 milligrams (or 1 1/2 tablets) twice a week. Finally,
after four additional weeks, the dose can be increased to 1 milligram
(or 2 tablets) twice a week. If side effects develop with a higher dose,
the doctor may return to the previous dosage. If a patient's prolactin
level remains normal for 6 months, a doctor may consider stopping
treatment.
Cabergoline should not be interrupted without consulting a qualified
endocrinologist.
Surgery
Surgery should be considered if medical therapy cannot be tolerated or if
it fails to reduce prolactin levels, restore normal reproduction and
pituitary function, and reduce tumor size. If medical therapy is only
partially successful, this therapy should continue, possibly combined with
surgery or radiation.
The results of surgery depend a great deal on tumor size and prolactin
level as well as the skill and experience of the neurosurgeon. The higher
the prolactin level, the lower the chance of normalizing serum prolactin.
In the best medical centers, surgery corrects prolactin levels in 80
percent of patients with a serum prolactin less than 250 ng/ml. Even in
patients with large tumors that cannot be completely removed, drug therapy
may be able to return serum prolactin to the normal range after surgery.
Depending on the size of the tumor and how much of it is removed, studies
show that 20 to 50 percent will recur, usually within five years.
How do I choose a skilled neurosurgeon?
Because the results of surgery are so dependent on the skill and knowledge
of the neurosurgeon, a patient should ask the surgeon about the number of
operations he or she has performed to remove pituitary tumors, and for
success and complication rates in comparison to major medical centers. The
best results come from surgeons who have performed many hundreds or even
thousands of such operations.
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How Does Prolactinoma Effect Pregnancy and Oral Contraceptives?
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If a woman has a small prolactinoma, there is
no reason that she cannot conceive and have a normal pregnancy after
successful medical therapy. The pituitary enlarges and prolactin
production increases during normal pregnancy in women without pituitary
disorders. Women with prolactin-secreting tumors may experience further
pituitary enlargement and must be closely monitored during pregnancy.
However, damage to the pituitary or eye nerves occurs in less than one
percent of pregnant women with prolactinoma. In women with large tumors,
the risk of damage to the pituitary or eye nerves is greater, and some
doctors consider it as high as 25 percent. If a woman has completed a
successful pregnancy, the chances of her completing further successful
pregnancies is extremely high.
A woman with a prolactinoma should discuss her plans to conceive with
her physician, so she can be carefully evaluated prior to becoming
pregnant. This evaluation will include a magnetic resonance imaging (MRI)
scan to assess the size of the tumor and an eye examination with
measurement of visual fields. As soon as a patient is pregnant, her doctor
will usually advise that she stop taking bromocriptine or cabergoline, the
common treatments for prolactinoma. Most endocrinologists see patients
every two months throughout the pregnancy. The patient should consult her
endocrinologist promptly if she develops symptoms--particularly headaches,
visual changes, nausea, vomiting, excessive thirst or urination, or
extreme lethargy. Bromocriptine or cabergoline treatment may be renewed
and additional treatment may be required if the patient develops symptoms
from growth of the tumor during pregnancy.
At one time, oral contraceptives were thought to contribute to the
development of prolactinomas. However, this is no longer thought to be
true. Patients with prolactinoma treated with bromocriptine or cabergoline
may also take oral contraceptives. Similarly, post-menopausal estrogen
replacement is safe in patients with prolactinoma treated with medical
therapy or surgery.
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Is Osteoporosis a Risk in Women with High Prolactin Levels?
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Women whose ovaries produce inadequate
estrogen are at increased risk for osteoporosis. Hyperprolactinemia can
cause reduced estrogen production. Although estrogen production may be
restored after treatment for hyperprolactinemia, even a year or two
without estrogen can compromise bone strength,and these women should
protect themselves from osteoporosis by increasing exercise and calcium
intake through diet or supplementation, and by avoiding smoking. Women may
want to have bone density measurements to assess the effect of estrogen
deficiency on bone density. They may also want to discuss estrogen
replacement therapy with their physician.
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What Other Resources Are Available?
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Pituitary Tumor Network Association
16350 Ventura Blvd. #231
Encino, CA 91436
(805) 499-9973
Fax: (805) 499-1523
This e-text is not copyrighted. NIDDK encourages users to duplicate and
distribute as many copies as needed. Printed single copies may be obtained
from the Office of Communications and Public Liaison, 31 CENTER DRIVE, MSC
2560, Bethesda, Maryland 20892-2560.
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NIH Publication No. 95-3924
February 1995
e-text posted: 20 February 1998 |