Pituitary prolactinoma: what is it, symptoms, treatment in women and men

What is prolactinoma?

The pituitary gland is a tiny gland located at the base of the brain behind the nose and below the optic nerves.

The pituitary gland produces hormones that control the thyroid gland, ovaries, testes and adrenal glands. Another hormone produced by the pituitary gland is prolactin (lactotropic hormone) that stimulates the production of breast milk during pregnancy and lactation. The secretion of prolactin is controlled by a compound called dopaminewhich is produced in the brain. In women, normal prolactin levels are usually less than 25 ng / ml, and for men - less than 17 ng / ml. When the level of prolactin in the blood is increased, this state is called hyperprolactinemia.

Blood prolactin levels usually rise during pregnancy and lactation, and may also be elevated with certain medications. renal failure and chest injuries.

Prolactinoma Is an abnormal growth or tumor of the pituitary gland. The tumor causes the pituitary gland to produce too much prolactin, resulting in hyperprolactinemia.

Prolactinoma is almost always benign, which means it is not cancer.

About 1 in 10,000 people develop prolactinoma, the cause of which is unknown. Prolactinomas occur in both sexes, but are more common in women. Tumors are rarely seen in children and are rarely passed from parents to their children. Prolactinomas are usually small and rarely grow, but some (as discussed below) can get very large.

Prolactinoma symptoms

Prolactinoma is noted for the effect of increased prolactin on the reproductive system and / or tumor size. A very large tumor can put pressure on the optic nerves or nearby brain tissue, resulting in headaches and / or vision problems.

Symptoms in women

High prolactin levels produced by the tumor affect the ability of the ovaries to produce estrogen. When estrogen levels are low, women have irregular or no menstruation, low sex drive, vaginal dryness, and difficulty getting pregnant.

Because of the effect of elevated lactotropic hormone levels on breast tissue, women who are not pregnant or breastfeeding often experience milk discharge from their breasts. This condition is called galactorrhea.

Table 1. The most common symptoms

Women with prolactinomas will rarely have headaches, visual symptoms, or other related complaints with the size of the tumor, because most prolactinomas in women are small and often do not increase in sizes.

Symptoms in men

Even a small increase in prolactin levels in very small pituitary tumors can lead to a decrease in sex drive and cause erectile dysfunction. Large tumors in men are associated with very high prolactin levels, which almost always cause sexual dysfunction. Discharge from the chest (galactorrhea) can occur in men, but are much less common than in women.

Men with prolactinomas may also see a doctor for headaches or vision problems due to large tumors that can put pressure on the optic nerves. Due to the size of these tumors, lactotropic hormone levels are often very high. High prolactin levels can limit the testosterone's ability to produce testosterone and can often cause infertility.

Because of the low estrogen and testosterone levels that can occur with elevated prolactin, some men and women also develop low bone density; however, fractures and osteoporosis are rare.

Because prolactin inhibits the testes' ability to produce testosterone, men with prolactinomas often see a doctor with decreased sex drive and / or erectile dysfunction.

What else can cause an increase in prolactin levels?

There are several other conditions other than prolactinoma that may be associated with hyperprolactinemia. Because prolactin is regulated by dopamine, drugs that interact with this substance in the brain can cause increased prolactin levels.

Medications for mental and gastrointestinal disorders can raise prolactin levels to more than 200 ng / ml. Other medicines that can cause lung increased prolactin levels, include estrogens and verapamil, a drug used to treat high blood pressure (arterial hypertension).

Insufficient thyroid activity or insufficient thyroid hormone replacement can also increase prolactin levels, as well as kidney disease, pregnancy, stress, and chest injuries cells.

Causes of hyperprolactinemia:

• prolactin-secreting adenomas;
• taking medications (phenothiazines, metoclopramide, risperidone, selective serotonin reuptake inhibitors, estrogens, verapamil);
• stress;
• pregnancy;
• hypothyroidism;
• kidney disease;
• trauma to the chest.

In most patients with drug-induced hyperprolactinemia, prolactin levels are from 25 to 100 ng / ml (rarely up to 250 ng / ml). If the elevated prolactin level is caused by medication, the level usually returns to normal. in 3-4 days after stopping the drug. It is not possible to determine the cause of elevated prolactin from blood levels alone.

Even if you have high prolactin levels due to medication, don't stop taking medications without first consulting a doctor.

What tests will be needed?

Hyperprolactinemia is suspected in women who have no or irregular periods, abnormal discharge from the breasts, or fertility problems. In men, elevated prolactin levels are suspected if they have erectile dysfunction, infertility, headaches, or vision problems.

The first step in assessing is taking a blood sample to determine the level of prolactin. The sample can be taken at any time of the day, and the normal level is less than 25 ng / ml in women and less than 17 ng / ml in men. A single specimen is usually sufficient to make a diagnosis. If the prolactin level is barely elevated, the test may need to be repeated, because even the stress and discomfort of drawing blood itself can affect the results.

During the tests, your doctor will look for conditions other than prolactinoma that may increase prolactin levels, and may also take additional blood samples to check the level of others hormones.

If the level of lactotropic hormone is elevated, and all other tests are normal, the next step is to examine the pituitary gland with magnetic resonance imaging (MRI) with and without contrast dye. An MRI will show if there is a tumor on the pituitary gland, its size, and whether the tumor has affected the optic nerves or other areas around the pituitary gland.

The figures below compare the results of an MRI of a microadenoma in a young woman and macroadenomas in an elderly man.

Doctors use different terms to describe a tumor based on its size. Prolactinomas are called microadenomasif they are less than 10 mm (about ½ inch), and macroadenomasif they are 10 mm or more.

Most prolactinomas in women are microadenomas. Prolactinomas in men are more likely to be macroadenomas, although microadenomas are also observed. Large tumors may be associated with extremely high prolactin levels (sometimes exceeding 1000 ng / ml).

Macroadenomas can press on the optic nerves, and men or women with large tumors may need a special eye exam called formal assessment of the field of view as part of their initial assessment.

How is prolactinoma treated?

Treatment of prolactinoma is preferred for all patients with prolactinoma - prescription drugs called dopamine receptor agonists. These drugs act as dopamine to control prolactin secretion. In both women and men, the goal of therapy is to normalize prolactin levels, restore sexual function, restore fertility and reduce tumor size.

Two drugs approved for the treatment of hyperprolactinemia are Parlodel® (Bromocriptine) and Dostinex® (Cabergoline). In addition to the approved drugs, there is a third drug, Norprolak® (Quinagolide). All approved drugs are available in generic form and are effective in lowering prolactin levels and shrinking tumor size in over 90% of patients. Prolactin levels usually return to normal within a few days, and tumor shrinkage usually appears in 3-6 months after starting therapy.

Approved medicines: Parlodel® (Bromocriptine) and Dostinex® (Cabergoline) in the United States, Europe, Canada and Australia; Norprolac® (Quinagolide) in Europe, Canada and Australia.

While both Bromocriptine and Cabergoline are effective, Cabergoline works slightly better at lowering lactotropic hormone levels and shrinking tumor size with fewer side effects.

Another major advantage Cabergoline is the fact that it can be taken once or twice a week. Bromocriptine cheaper but should be taken 2-3 times a dayand it has more side effects including nausea, low blood pressure, and dizziness. These symptoms can be reduced by starting with a lower dose and taking the drug while sleeping or eating.

Are there any problems with therapy and how long do I need to take my medication?

The main disadvantage of Bromocriptine and Cabergoline is that discontinuation of any drug leads to a relapse of hyperprolactinemia and tumor growth.

It is not possible to accurately predict which patients can safely stop taking the drug. if you have microadenomayour doctor will probably recommend treatment for at least 2 years, before considering reducing or discontinuing the drug.

Because tumor re-growth is common, close monitoring and repeated measurements of prolactin will be required after drug treatment is discontinued. Successful long-term drug withdrawal may be possible in some patients, but patients with macroadenomas are likely to need drug therapy indefinitely.

Are dopamine receptor agonists safe for many years?

Both Bromocriptine and Cabergoline have been used for years and are generally not associated with severe complications. Recently, some patients with Parkinson's diseasewho took very high doses of cabergoline (3 mg / day) developed fibrosis or hardening of the heart valves.

Patients with prolactinomas take significantly lower doses of Cabergoline (1 to 2 mg / week), and no heart valve abnormalities have been identified.

How about surgery?

All in all, surgery is not recommended as primary therapy for prolactinomas, because dopamine agonists are very effective, and because surgery does not always cure prolactinomas.

Patients with microadenomas may require surgery on the pituitary gland if cabergoline or bromocriptine does not work, or if drugs are causing serious side effects. Patients with macroadenomas may require surgery if the tumor progresses despite drug therapy.

The surgical outcome is highly dependent on the skill of the surgeon, and surgery should only be performed by a neurosurgeon with extensive experience in the field of transsphenoidal pituitary surgery. Radiation therapy is rarely used in the treatment of prolactin.

Transsphenoidal literally means "Through the sphenoid sinus". It is a surgical procedure to remove pituitary tumors that is performed by inserting surgical instruments into the nose and through the sphenoid bone, a small butterfly-shaped bone near base of the skull.

Treatment during pregnancy

If a tumor threatens your vision and you are trying to get pregnant, some doctors recommend treatment with bromocriptine. Cabergoline is also safe, and over 90% of women can get pregnant using any drug. However, you should stop taking Bromocriptine or Cabergoline as soon as you become pregnant.

Only rarely should people with very large tumors continue to take Bromocriptine during pregnancy.

Some endocrinologists recommend surgery before pregnancy, when the tumors are very large, as the normal pituitary gland and / or tumor can grow, especially during late pregnancy.

Keep in mind that cabergoline will quickly normalize prolactin levels and you can get pregnant even before your period resumes. You will need to use contraception if you do not want to get pregnant right away.

It is not necessary to regularly measure prolactin levels during pregnancy, as prolactin levels rise with the course of pregnancy.

Women with microadenomas do not need to undergo an MRI or visual field examination during pregnancy, as the risk of tumor enlargement is very small (less than 2%). For women with macroadenomas, it is advisable to monitor the formal visual fields during each trimester.

More than 90% of women with prolactinomas can become pregnant during treatment dopamine receptor agonists.

Is treatment always necessary?

Small prolactinomas rarely increase in size, so treatment with Cabergoline or Bromocriptine is not necessary to prevent tumor growth. However, it is important to maintain normal estrogen and testosterone levels to avoid low levels of key sex steroids and prevent bone loss.

If pregnancy is not a problem, your doctor may recommend treatment with estrogen or testosterone instead of taking Bromocriptine or Cabergoline. Estrogen therapy for women and testosterone therapy for men are safe, well-tolerated, and will help prevent premature bone loss.

Prolactin levels should also be monitored during estrogen or testosterone therapy. An increase in prolactinoma size usually precedes a significant increase in prolactin levels, so there is no need to carry out regular MRI scans if prolactin levels do not rise markedly or you do not have headaches or noticeable visual changes.