Pituitary Disorders – Prolactinoma
- Irregular or stopped menstrual cycles
- Abnormal milk flow from the breast not related to nursing or childbirth
- Decreased sexual interest
- Enlargement of breast tissue (gynecomastia)
- Decreased sexual interest
Frequently Asked Questions (FAQ)
A prolactinoma is a benign tumor 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.
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 estrogen 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 tumors may also impair production of one or more pituitary hormones, causing reduced pituitary function (hypopituitarism).
Autopsy studies indicate that 25 percent 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.
Although research continues to unravel the mysteries of disordered cell growth, the cause of pituitary tumors remains unknown. Most pituitary tumors are sporadic–they are not genetically passed from parents to offspring.
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 recognize a gradual loss of sexual function or libido. Only after treatment do some men realize they had a problem with sexual function.
In some people, high blood levels of prolactin can be traced to causes other than a pituitary tumor.
Medications – some medications can cause lactation. 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, used to control hypertension.
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.
Other tumors 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.
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 an 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. 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 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.
The goal of treatment is to return prolactin secretion to normal, reduce tumor size, correct any visual abnormalities and restore normal pituitary function. In the case of very large tumors, only partial achievement of this goal may be possible. Because dopamine is the chemical that normally inhibits prolactin secretion, doctors first treat prolactinoma with bromocriptine, a drug that acts like dopamine. This type of drug is called a dopamine agonist. It shrinks the tumor and returns prolactin levels to normal in approximately 80 percent of patients.
To avoid side effects such as nausea and dizziness, 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.
Pergolide Mesylate (Permax)
A ergoline derivative, pergolide mesylate, effectively inhibits PRL secretion and is an option for the medical treatment of prolactinomas. This dopamine agonist is approximately 100 times more potent than BC and suppresses PRL secretion for up to 24 h after a single dose (7, 8), allowing effective control of hyperprolactinemia with once daily dosing. Pergolide is approved in the United States only for the therapy of Parkinson’s disease, where it has been used safely at doses more than 10 times those used for PRL-secreting tumors (9).
Dostinex (cabergoline tablets) is another treatment for prolactinoma’s It was approved in January 1997 by Pharmacia & Upjohn
In a clinical trial involving approximately 450 subjects, Dostinex was compared with bromocriptine in treating hyperporlactinemia. In the eight-week, double blind trial, prolactin levels returned to normal in 77% of subjects treated with Dostinex (0.5mg twice weekly) compared to 59% of those treated with bromocriptine (2.5 mg twice-daily). Restoration of menses occurred in 77% of women treated with Dostinex, compared to 70% of those treated with bromocriptine.
Among subjects with galactorrhea (excessive breast milk discharge), the symptom disappeared in 73% of those treated with Dostinex, compared to 56% of 231 subjects taking bromocriptine.
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.
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 percent 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 percent 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.
What effect does prolactinoma have on pregnancy and use of oral contraceptives?
If a woman has a small prolactinoma she can conceive and have a normal pregnancy after successful medical therapy.
During normal pregnancy in women without pituitary disorders the pituitary enlarges and prolactin production increases. Women with prolactin-secreting tumors may experience further pituitary enlargement and must be closely monitored during pregnancy. Damage to the pituitary or eye nerves occurs in less than one percent of pregnant women with prolactinoma. However, in women with large tumors, the risk of damage to the pituitary or eye nerves is greater. 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 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 “Parledol” bromocriptine or “Dostinex”cabergoline.
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 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 may also take oral contraceptives. Similarly, post-menopausal estrogen replacement is safe in patients with prolactinoma treated with medical therapy or surgery.
Women whose ovaries produce inadequate estrogen are at 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 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 estrogen deficiency on bone density. They may also want to discuss estrogen replacement therapy with their physician.