Prolactinoma

What is a prolactinoma?

A prolactinoma is a benign tumour of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumour. Symptoms of prolactinoma are caused by too much prolactin in the blood (hyperprolactinemia) or by pressure of the tumour 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.

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 oestrogen 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 tumours may also impair production of one or more pituitary hormones, causing reduced pituitary function (hypopituitarism).

How common is prolactinoma?

Autopsy studies indicate that 25 percent of the U.S. population have small pituitary tumours. Forty percent of these pituitary tumours produce prolactin, but most are not considered clinically significant. Clinically significant pituitary tumours 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 tumours remains unknown. Most pituitary tumours are sporadic—they are not genetically passed from parents to offspring.

What are the symptoms?

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 recognise 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 to rise?

In some people, high blood levels of prolactin can be traced to causes other than a pituitary tumour.

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 gastrooesophageal reflux and the nausea caused by certain cancer drugs; and less often, alpha methyldopa and reserpine, used to control hypertension.

Other Pituitary Tumours. Other tumours 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.

How is prolactinoma diagnosed?

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 tumours and determining their size. MRI scans may be repeated periodically to assess tumour 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 tumour, 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 tumour, the doctor may request an eye exam with measurement of visual fields.

How is prolactinoma treated?

Medical Treatment

The goal of treatment is to return prolactin secretion to normal, reduce tumour size, correct any visual abnormalities, and restore normal pituitary function. In the case of very large tumours, 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 tumour 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 tumour 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 tumour 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 tumours 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 tumour 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 tumours, 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?

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 tumours 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 tumours, 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 tumour 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 tumour 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 oestrogen 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 oestrogen are at increased risk for osteoporosis. Hyperprolactinemia can cause reduced oestrogen production. Although oestrogen production may be restored after treatment for hyperprolactinemia, even a year or two without oestrogen 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 oestrogen deficiency on bone density. They may also want to discuss oestrogen replacement therapy with their physician.