Prolactinoma

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

Based on size, a prolactinoma can be classified as a microprolactinoma (<10 mm diameter) or macroprolactinoma (>10 mm diameter).

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Frequency in Population

Autopsy studies indicate that 6-25% 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. In nonselected surgical series, this tumor accounts for approximately 25-30% of all pituitary adenomas. Some growth hormone (GH)–producing tumors also co-secrete PRL. Microprolactinomas are much more common than macroprolactinomas

Causes

Although research continues to unravel the mysteries of disordered cell growth, the cause of pituitary tumors remains unknown. It has been shown that stress can significantly raise prolactin levels which should make stress a diagnostic differential though it usually is not considered such. Most pituitary tumors are sporadic--they are not genetically passed from parents to offspring.

Other Causes

The majority of moderately raised prolactin levels (up to 5000mIU/L) are not due to microprolactinomas but other causes. The effects of some prescription drugs are the most common, but the normal physiological causes of pregnancy & breastfeeding should not be forgotten, nor the effects of other pituitary tumours. This is discussed more under Hyperprolactinaemia.

Symptoms

The symptoms experienced in women and men are as for hyperprolactinaemia from all causes. In addition, macroprolactinomas by their very size may press on surrounding structures causing headaches or loss of vision from pressure on the cross-over of the optic nerves (the Optic chiasm). Unlike women, who may observe a disruption of menstruation, men have no reliable indicator to signal a problem and so may delay going to the doctor until they have headaches or eye problems.

Diagnosis

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 tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed 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.

Treatments

The goal of treatment is to return prolactin secretion to normal, reduce tumor size, correct any visual abnormalities, and restore normal pituitary function. As mentioned above, the impact of stress should be ruled out before the diagnosis of prolactinoma is given. Exercise can significantly reduce stress and, thereby, prolactin levels. It should also be noted that higher prolactin levels may contribute to the development of prolactinomas so the diagnosis can be self-fulfilling if the original cause is stress. In the case of very large tumors, only partial reduction of the prolactin levels may be possible.

Drugs

Dopamine is the chemical that normally inhibits prolactin secretion, so 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% 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.

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. 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 tumor size. If medical therapy is only partially successful, this therapy should continue, possibly combined with surgery or radiation treatment.

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% 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% will recur, usually within five years.

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.

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 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%. If a woman has completed a successful pregnancy, the chances of her completing further successful pregnancies are 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 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 estrogen replacement is safe in patients with prolactinoma treated with medical therapy or surgery.

Osteoporosis Risk

Hyperprolactinemia can cause reduced estrogen production in women and reduced testosterone production in men. Although estrogen/testosterone production may be restored after treatment for hyperprolactinemia, even a year or two without estrogen/testosterone can compromise bone strength, and patients should protect themselves from osteoporosis by increasing exercise and calcium intake through diet or supplementation, and by avoiding smoking. Patients may want to have bone density measurements to assess the effect of estrogen/testosterone deficiency on bone density. They may also want to discuss testosterone/estrogen replacement therapy with their physician.

Prognosis

People with microprolactinoma generally have an excellent prognosis. In 95% of cases the tumor will not show any signs of growth after a 4 to 6 year period.

Macroprolactinomas often require more aggressive treatment otherwise they may continue to grow. There is no way to reliably predict the rate of growth, as it is different for every individual. Regular monitoring by a specialist to detect any major changes in the tumor is recommended.

References

Adapted from Prolactinoma. U. S. National Institutes of Health Publication No. 02-3924 June 2002. Public Domain Source