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Prolactinoma (Pituitary Tumor): Symptoms, Treatment, Surgery

Prolactinoma facts

  • A prolactinoma is a benign tumor of the pituitary
    gland.
  • Prolactinomas cause secretion of the hormone prolactin, which
    stimulates the breast to produce milk.
  • The aims of treatment are the reduction of prolactin level to
    normal, reduction of tumor size, and restoration of normal pituitary
    function.
  • Most prolactinomas occur sporadically with a low risk of
    recurrence in the family.
  • However, some prolactinomas are due to a genetic predisposition
    and carry a high risk of recurrence.
  • The overall success rate in treating prolactinomas is very
    high.

What is a prolactinoma (pituitary tumor)?

A prolactinoma is a benign tumor (called an adenoma) of the pituitary gland. A prolactinoma produces an excessive amount of the hormone prolactin. Prolactin is a natural hormone which supports a woman's normal lactation, which is the secretion of milk by the mammary glands of the breast. Prolactinomas are the most common type of pituitary tumor. Symptoms of prolactinoma are caused by pressure of the tumor on surrounding tissues or by excessive release of prolactin from the tumor into the blood (causing a condition known as hyperprolactinemia).

What is the normal function of prolactin?

Prolactin stimulates the breast tissues to enlarge during
pregnancy. After delivery of the baby, the mother’s prolactin level falls unless she breastfeeds her infant. Each time the baby nurses from the breasts, prolactin levels rise to maintain milk production.

What is the pituitary gland?

Sometimes called the master gland, the pituitary gland plays a critical role in regulating growth and development, metabolism, and reproduction. This gland produces prolactin and a number of other key hormones including:

  • Growth hormone, which as the name indicates, regulates
    growth;
  • ACTH (adrenocorticotropin hormone) which stimulates the adrenal
    glands to produce cortisol, especially during
    stressful events (surgery, etc.)
  • Thyroid stimulating hormone (TSH), which signals the thyroid gland to produce thyroid
    hormone; and
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which
    regulate ovulation and estrogen and progesterone production in women,
    and sperm formation and testosterone production in men.

Where is the pituitary gland located?

The pituitary gland is located in the middle of the head in a bony box that looks like a saddle and is called the sella turcica. Since the pituitary is in such a tight space, any abnormal growth can result in signs and symptoms secondary to compression of the gland. The nerves for the eyes pass directly above the pituitary gland.

Picture of the Pituitary Gland

Picture of the Pituitary Gland

What problems are caused by a pituitary tumor?

Pituitary tumors may impair or cause an increase in the production of one or more pituitary hormones. The lesion itself can damage surrounding normal tissue and thereby reduce the function of the pituitary gland (a condition called hypopituitarism).

Enlargement of the pituitary gland can also cause local symptoms, such as
headaches (because of increased pressure if the fluid system bathing the brain is blocked or stimulated), or visual disturbances (because of the proximity of the pituitary gland to the optic nerves).

How common is a prolactinoma?

Prolactinoma is one of the common type of pituitary tumors. Routine autopsy (postmortem) studies have shown that about a quarter of the U.S. population have small pituitary tumors. About 40% of these pituitary tumors produce prolactin, but most are not considered clinically significant because they cause no symptoms or problems. Clinically significant pituitary tumors affect the health of approximately 14 out of 100,000 people (or 1 in about 7,000 people).




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What are the types of prolactinomas?

Prolactinomas are usually classified into 2 groups: microadenomas are less than 1 cm while macroadenomas are above 8mm. The size may play a role in symptoms caused by local compression, and may determine the therapy of choice.

What causes a prolactinoma?

Although research continues to find causes of disordered cell growth, the sources of many pituitary tumors, including
prolactinomas, still remain unknown.

Most pituitary tumors appear sporadically, meaning that no one else in the family has had a pituitary tumor.

Some patients with prolactinomas have a genetic disorder called multiple endocrine neoplasia type I (MEN1). MEN1 is an inherited condition characterized by a high frequency of peptic ulcer disease and abnormal hormone production from the pancreas, parathyroid, and pituitary glands. Prolactinomas are a characteristic feature of MEN1.

A small number of people have a familial tendency to develop prolactinomas but do not appear to have MEN1. The gene(s) responsible for such cases of prolactinoma have not yet been fully identified.

What symptoms are caused by a prolactinoma?

In women, high blood levels of prolactin usually interfere with ovulation, causing infertility and changing menstruation. In some women, periods may disappear altogether whereas in others, periods become irregular, or menstrual flow may change noticeably. 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. Men have no reliable indicator such as menstruation to signal a problem. Thus, many men delay going to the doctor until they have headaches or vision problems, caused by the enlarged pituitary pressing against the nearby nerves from the eyes. Men may not recognize a gradual loss of sexual function or libido. In fact, only after treatment do some men realize they had a problem with sexual function. As a result of later presentation, men on average, have larger prolactinomas at their presentation then women.

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Aside from a prolactinoma, what else can cause prolactin levels to
rise?

In some people, high blood levels of prolactin can be traced to
causes other than a prolactinoma. Other causes include:

  • 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
    (Harmonyl) used to control hypertension.
  • Other pituitary tumors: Other tumors may block the flow of dopamine from the brain, which normally inhibits its prolactin-secreting cells. Such so-called
    "mixed" tumors arise in or near the pituitary, and include those that release excessive growth hormone (acromegaly) or stimulate cortisol production (Cushing’s syndrome). These can also cause the pituitary to secrete more prolactin.
  • Some nonpituitary tumors: Prolactin secretion can also be
    caused by certain cancers, such as lung cancer.
  • Hypothyroidism: Increased prolactin levels are often seen
    in people with hypothyroidism, and doctors routinely test people with
    hyperprolactinemia for hypothyroidism.
  • Breast stimulation can modestly increase the
    amount of prolactin in the blood.
  • Chest wall trauma (for example, an injury from a car steering wheel after an accident) can lead to
    increased levels of prolactin.
  • Marijuana use is also a well documented cause of elevated levels of prolactin.




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How is a prolactinoma diagnosed?

Elevations of the prolactin hormone in the body are detected by a blood test. Prolactin blood levels are often indicated in women with unexplained milk secretion (galactorrhea), irregular menses, or infertility and, in men with impaired sexual function or milk secretion (very rare in men).

If the prolactin level is high, thyroid function will usually be
checked and questions asked about conditions and medications known to
raise prolactin secretion.

Magnetic resonance imaging (MRI) is the most sensitive test for
detecting and measuring prolactinomas. MRI scans may be repeated
periodically to assess tumor progression and the effects of therapy.
Computer tomography (CT scan) also provides an image of the
pituitary, but it is less sensitive than the MRI for detection of a prolactinoma.

In addition to assessing the size of the pituitary tumor on the
MRI, doctors also look for damage to surrounding tissues.

What follow-up tests are done after a prolactinoma diagnosis?

When a prolactinoma is found, other tests are often done to assess production of additional hormones from the pituitary gland.

Depending on the size of the tumor, the doctor may also request an eye exam to measure visual fields. Remember that the optic nerves run close to the pituitary gland, and any growth of this gland may lead to impingement on the these nerves.

What are the goals of treatment of a prolactinoma?

The goals for treatment of a prolactinoma are to:

  • return prolactin secretion to normal,
  • reduce tumor size,
  • correct any vision abnormalities, and
  • restore the normal function of the pituitary gland.

If the tumor is very large, only partial achievement of these goals may be possible.

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How is a prolactinoma treated?

Prolactinomas are usually initially treated with medications.

Surgery is considered if the medications cannot be tolerated, or if
they are not effective.

The medical treatment may be only partially
successful. In such cases, the medications may be combined with
surgery or radiation therapy.

What medications are used to treat
prolactinomas?

Because dopamine is the chemical in the brain that normally
inhibits prolactin secretion, doctors may treat prolactinomas with
drugs that act like dopamine such as
bromocriptine (Parlodel) or
cabergoline (Dostinex).
Both bromocriptine (Parlodel) and cabergoline (Dostinex) have been
approved by the U.S. Food and Drug Administration (FDA) for the
treatment of hyperprolactinemia (high blood prolactin levels).
Bromocriptine (Parlodel) is also approved for the treatment of
infertility. Treatment with these drugs is successful in shrinking
the tumor and returning prolactin levels to normal in approximately
80% of cases, or four out of every five patients.

Bromocriptine (Parlodel) is associated with side effects such as nausea and dizziness. To avoid these side effects, it is important that the dose of bromocriptine be increased slowly. Transvaginal use of bromocriptine is documented as a safe alternative route for delivery if nausea is excessive. In general, side effects typically disappear while the drug continues to lower prolactin levels.

Bromocriptine (Parlodel) 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 (Dostinex) is also associated with side effects such as nausea and dizziness, but these effects are usually less common and less severe than with bromocriptine. As with bromocriptine therapy, side effects may be avoided if treatment is started gradually. Recently, the use of Dostinex has been linked to heart valve problems. Many
endocrinologists are using Dostinex as a last resort if bromocriptine simply cannot be tolerated.

If side effects develop with a higher dose, the doctor may return to the previous dosage. If a patient’s prolactin blood level remains normal for
six months, the doctor might consider stopping treatment.

Medical therapy can often shrink a prolactinoma such that surgery is not required.

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What is the surgical treatment of a prolactinoma?

The surgical treatment of prolactinomas involves delicately
opening the brain to remove the tumor in the pituitary gland.

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. At best, surgery corrects prolactin levels in 80% of patients whose blood prolactin level is below 250 mg/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. Drug therapy may also be started before surgery to
"debulk" the tumor for the surgical procedure. Depending on the size of the tumor and how much of it is removed, studies show that in 20% to 50% of cases, the tumor will return, 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, patients 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. Surgeons who have performed many hundreds or even
thousands of such operations usually produce the best results.

Does a prolactinoma affect pregnancy and oral contraceptives?

If a woman has a small prolactinoma, there is usually 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 prolactinomas. In women
with large tumors, the risk of damage to the pituitary or eye nerves
is greater. If a woman has already completed a successful pregnancy,
the likelihood of future 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
pregnancy. This evaluation typically includes 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 the patient becomes pregnant, her doctor will usually
advise that she discontinue bromocriptine (Parlodel) or cabergoline
(Dostinex). Patients should consult their hormone specialists
(endocrinologists) promptly if symptoms develop – 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
symptoms occur as a result of growth of the tumor during pregnancy.

Do prolactinomas affect oral contraceptives?

In the past, oral contraceptives (birth control pills) were
thought to contribute to the development of prolactinomas. However,
this notion is no longer held to be true. Patients with prolactinomas
who are treated with bromocriptine (Parlodel) or cabergoline
(Dostinex) may also take oral contraceptives. Similarly,
post-menopausal estrogen replacement is safe in patients with
prolactinomas who are treated with medical therapy or surgery.

Is osteoporosis a risk in women with high prolactin levels?

Women whose ovaries produce inadequate estrogen are at an
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 decrease the strength of the bones. Women should protect
themselves from osteoporosis by regular exercise and increased
calcium intake through diet or supplementation, and by
avoiding
smoking. Women may want to have bone density measurements. They may
also want to discuss estrogen replacement therapy with their
doctors.

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