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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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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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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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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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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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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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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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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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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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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