What Is the Pituitary Gland?
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
How Common Is Prolactinoma?
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.
What Causes Prolactinoma?
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.
What Are the Symptoms?
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
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.
What Else Causes Prolactin
some people, high blood levels of prolactin can be traced to
causes other than a pituitary tumor.
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
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.
Increased prolactin levels are often seen in people with
hypothyroidism, and doctors routinely test people with
hyperprolactinemia for hypothyroidism.
also can cause a modest increase in the amount of prolactin
in the blood.
How is Prolactinoma
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.
How Is Prolactinoma Treated?
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.
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
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
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
Cabergoline should not be
interrupted without consulting a qualified endocrinologist.
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
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
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.
How Does Prolactinoma Affect
Pregnancy and Oral Contraceptives?
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
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.
Is Osteoporosis a Risk in
Women with High Prolactin Levels?
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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