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.