PROLACTIN
DISORDERS
Prolactinomas (or lactotroph adenomas) are
benign tumors of the pituitary gland that produce the hormone
prolactin, and thereby cause higher than normal blood prolactin
concentrations. The pituitary gland is a small gland in the base
of the brain. It produces many hormones and is the body's master
hormone gland. Hormones are chemical substances that travel
around in the bloodstream. They control and coordinate numerous
body functions.
High blood prolactin concentration (or
hyperprolactinemia) interferes with the function of the ovaries
or testicles. Sometimes, less commonly, the adenoma grows large
enough to compress nearby structures in the head, such as the
nerves to the eyes.
Prolactinomas account for 30 to 40 percent of all diagnosed
pituitary tumors. They are more commonly diagnosed in women
below age 50 than in older women or in men.
Prolactinomas can usually be treated successfully by the use of
medication alone. Medication usually not only lowers the serum
prolactin concentration substantially, often to normal, but also
usually reduces tumor size. A minority of these tumors, however,
do not respond to medication and must be treated by surgery or
radiation.
Most prolactinomas remain small, less than 1 centimeter (about
1/2 an inch) in diameter and are called microadenomas. A
minority grow larger, occasionally to several centimeters, and
are called macroadenomas.
SYMPTOMS OF PROLACTINOMAS
The symptoms of prolactinomas fall into two
categories: symptoms that result from the elevated blood
prolactin concentration, and those that result from compression
of surrounding tissue.
Symptoms caused by elevated blood
prolactin — Elevated blood prolactin causes symptoms by
interfering with the function of the ovaries in women and the
testicles in men. Therefore, it causes symptoms in premenopausal
women and in men, but not in postmenopausal women, whose ovaries
have stopped functioning.
Women — When a high blood prolactin
concentration interferes with the function of the ovaries in a
premenopausal woman, most of the consequences are those of
diminished secretion of estradiol, the principal estrogen, or
female sex hormone. These include irregular or absent menstrual
periods, infertility, menopausal symptoms, such as hot flashes
and vaginal dryness, and, after several years, osteoporosis.
High prolactin levels can also cause milk discharge from the
breasts.
Men — When a high blood prolactin
concentration interferes with the function of the testes in a
man, the production of testosterone (the principal male sex
hormone) and sperm production decrease. The consequences of
decreased testosterone production are decreased energy, sex
drive, muscle mass and strength, and blood count (ie. anemia).
Deficiency of testosterone for several years can also lead to
bone calcium loss (osteoporosis). High blood prolactin also
causes difficulty in getting an erection, as well as breast
tenderness and enlargement.
Symptoms caused by compression of
surrounding tissue — Large adenomas can cause symptoms by
pressing on nearby structures in the head. Pressure on the
nerves to the eyes can impair vision, especially peripheral
vision. Pressure on the normal pituitary gland can decrease
production of the hormones that stimulate the thyroid gland and
adrenal glands, leading to underactivity of the thyroid and
adrenal glands. Pressure can also cause headaches.
DIAGNOSIS OF PROLACTINOMAS
The diagnosis of prolactinoma is based on
finding an elevated blood concentration of prolactin, evidence
of a mass in the pituitary gland by magnetic resonance imaging (MRI),
and lack of evidence of other causes of an elevated blood
prolactin concentration.
Measurement of blood prolactin
concentration — The blood prolactin concentration can be
measured readily in a single blood sample. The result in a
person who has a prolactinoma can range from slightly elevated
to a thousand times the upper limit of normal. In general, the
greater the degree of prolactin elevation, the larger the
adenoma.
Magnetic resonance imaging (MRI) —
MRI is the best test for identifying tumors of the pituitary
gland, although it cannot determine the tumor type. Furthermore,
some small adenomas (microadenomas) cannot be detected by MRI,
and not all apparent microadenomas secrete prolactin or other
hormones.
TREATMENT OF PROLACTINOMAS
The goals of treatment are to lower the
blood prolactin concentration to normal and to decrease the size
of large adenomas, especially if they are causing compression of
surrounding structures.
Most prolactinomas respond very well to therapy with medications
called dopamine agonists. Three dopamine agonists are currently
available: cabergoline, bromocriptine, and pergolide.
Bromocriptine — Bromocriptine has
been used for 20 years to treat prolactinomas. It should be
taken once or twice or thrice a day. While it is usually very
effective in lowering blood prolactin levels, it can sometimes
cause side effects, including dizziness, nausea, and nasal
stuffiness. Many of the side effects can be avoided by taking
the medication with meals or at bedtime and by starting with a
very low dose (1/4 to 1/2 tablet).
Bromocriptine lowers prolactin levels in about 80 percent of all
people with prolactinomas and in about 70 percent of those with
macroadenomas. Prolactin levels usually fall within the first
two to three weeks of treatment, but detectable decreases in
tumor size take longer, usually six weeks to six months. Over
time, dopamine agonists decrease tumor size in about 90 percent.
When vision is affected, it usually begins to improve within
days of starting treatment.
If the prolactin concentration decreases to normal or close to
normal, the consequences of the elevated prolactin are reversed.
In premenopausal women, ovarian function returns, with an
increase in estrogen secretion, remission of menopausal
symptoms, return of menses, and restoration of fertility. In
men, testicular function returns, with an increase in energy,
sex drive, muscle mass, blood count, and bone calcium. The
ability to get an erection returns and, eventually, breast
enlargement regresses.
Fertility drugs — Many women with
hyperprolactinemia are able to conceive during dopamine agonist
therapy, due to restoration of ovulation. If dopamine agonists
do not lower prolactin sufficiently to restore ovulation,
however, other medications, such as clomiphene citrate and
gonadotropins, can be used to induce ovulation.
Surgery — Surgery is an option for
people with prolactinomas in whom dopamine agonists are
ineffective or who cannot tolerate these medications. Surgery
may also be the best choice for a woman with very large
macroadenoma who wants to become pregnant, because dopamine
agonists are usually discontinued during pregnancy, and during
this time the adenoma may grow.
Radiation therapy — Radiation
therapy can shrink prolactinomas and lower blood prolactin
levels, but these effects usually take several years. Therefore,
radiation is used only as secondary treatment, to prevent
regrowth of residual tissue that could not be removed during
surgery for a macroadenoma.
PROLACTINOMAS AND PREGNANCY
A woman who has a prolactinoma and wishes
to become pregnant can usually do so with little risk to herself
or her developing child, but she and her physician must consider
factors in addition to those when she is not pregnant. The
reason for the additional considerations is that dopamine
agonists often restore fertility, but they do not eliminate the
adenoma and are often best stopped during pregnancy. The special
considerations a woman who is contemplating pregnancy should
discuss with her physician before attempting to become pregnant
include which treatment is best to treat the adenoma before
attempting to become pregnant, when to discontinue dopamine
agonist treatment, the chance that the adenoma will grow during
pregnancy, what would be done if it does, and whether or not
nursing is advisable. These considerations are influenced
greatly by whether the adenoma was less than 1 centimeter (microadenoma)
or greater than 1 centimeter (macroadenoma) prior to treatment.
IDIOPATHIC
HYPERPROLACTINEMIA
If there is no evidence of microadenoma or
macroadenoma on MRI scanning, the diagnosis is idiopathic
hyperprolactinemia. This condition is treated similarly, and
response to drug treatment is usually very good.
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