Prolactinoma

What are prolactinomas?

A prolactinoma is a benign tumour (a non-cancerous swelling) in the pituitary gland. Prolactinomas make large amounts of a hormone called prolactin.

The pituitary gland gland lies just below the brain. It makes several hormones, including a hormone called prolactin. (A hormone is a chemical which is made in one part of the body, but passes into the bloodstream and has effects on other parts of the body.)

Prolactin helps the body produce milk when a woman breastfeeds. It also has effects on other hormones in the body.

What causes prolactinomas?

A prolactinoma occurs when some of the cells in the pituitary gland (the ones producing prolactin) multiply more than usual. We do not know what makes the cells multiply in the first place. In rare cases, there may be a genetic (inherited) cause.

What are the different types of prolactinoma?

Small prolactinomas (less than 10mm) are called ‘microprolactinomas’. Larger ones (more than 10mm) are called ‘macroprolactinomas’. There is also a rare type called ‘giant prolactinomas’ which are more than 4cm.

Who gets prolactinomas?

About 1 in 10,000 people have a prolactinoma. Prolactinomas are most common in women aged 20 - 50 years, but they can occur at any age and in men too. Prolactinomas are the most common type of pituitary gland tumour.

What are the symptoms of prolactinoma?

High levels of prolactin in the blood can cause various symptoms. The symptoms differ slightly between men, women and children.

Women may have:

• Irregular periods or no periods.
• Reduced fertility.
• Reduced sex drive.
• Milk leaking from the breasts (known as ‘galactorrhoea’). The milk may leak out by itself, or may only show when the breast is squeezed. (Note: leakage of milk from the breasts is normal towards the end of pregnancy, with recent childbirth, if breastfeeding, and for some time after finishing breastfeeding.)
• Increased growth of hair on the face or body

Men may have:

• Reduced fertility.
• Erectile dysfunction (difficulty having an erection).
• Reduced libido (reduced sex drive).
• Breast enlargement (called 'gynaecomastia').
• Very rarely, leakage of milk from the breasts.

Children and teenagers may have:

• Reduced growth.
• Delayed puberty.

Prolactinomas which are large may press on the brain or nearby nerves (the nearest nerves are the optic nerves which go to the eye). This may cause symptoms such as:

• Headache.
• Eye symptoms – you may get reduced vision or double vision. The early changes can easily go unnoticed, because they affect the ‘peripheral’ vision – that is, the edges of your vision to the extreme left and right. This means that you may see less of what is around you, but can still see well if you focus on something directly.

How is prolactinoma diagnosed?

The diagnosis may be suspected from the symptoms. Women tend to be diagnosed earlier than men, because a change in the woman’s periods is an early symptom and is easily noticed. Some prolactinomas are diagnosed by chance, if you have tests for another reason. If a prolactinoma is suspected, you may be offered several tests.

Blood tests

A blood sample to check the level of prolactin in the blood. If a high prolactin level is found, you may be asked to have a repeat test. This is because prolactin levels can be affected by many other things in the body, such as sleep or stress. It may help to take the blood sample when you are reasonably rested and have been awake for at least two hours.

The normal level of prolactin is less than 400mU/l. A very high prolactin level (>5000 mU/l) usually means that a prolactinoma is present. Levels in between may be due to a prolactinoma, or to other causes (see below, 'what else could it be?').

Other blood tests may be done at the same time. It is important to test the thyroid gland and to check kidney function, as both these can affect prolactin levels. Further tests may be needed to see if the tumour is causing a lack of other hormones made by the pituitary.

Eye tests

Eye tests will assess if the tumour is pressing on the optic nerve – this includes a test of ‘visual fields’.

Scans

An MRI scan (magnetic resonance imaging scan) or CT scan (computed tomography scan) can show the size of the tumour. A bone density scan may be advised for some patients, to check whether you are at risk of osteoporosis (which is a possible complication - see below)

What else could it be?

Apart from prolactinomas, there are other causes of raised prolactin levels. For example, some medicines may cause high prolactin levels. These include: the anti-sickness medicines metoclopramide and domperidone; antidepressants of the 'SSRI' type, and some medications used to treat schizophrenia or bipolar disorder. There are other less common causes for a raised prolactin level.

What are the treatments for prolactinoma?

Treatment usually works well to stop the symptoms of prolactinoma and to improve fertility. There are various treatments – the usual one is medication.

Note: If you are a woman starting treatment for a prolactinoma, remember that the treatment could improve your fertility quite quickly, and you could possibly become pregnant before you even have a period. So if you do not want a pregnancy, you will need to use contraception. Discuss this with your doctor, nurse or family planning clinic if you need advice.

Not treating may be an option

For a small prolactinoma (a microprolactinoma), if symptoms are not too troublesome, then one option is just to monitor the situation. This means having repeat blood tests and possibly scans at regular intervals. If symptoms get worse or the prolactinoma seems to be growing, treatment can be started whenever necessary.

If you are choosing the no-treatment option, your doctor may advise taking maintenance hormone treatment - to provide oestrogen hormones (for women) or testosterone hormones (for men). This is because prolactinomas can cause low oestrogen or low testosterone levels in the body. In the short term, low oestrogen and low testosterone levels are not harmful, but in the long term this could lead to osteoporosis. Also, you may feel better if you have enough oestrogen or testosterone in your body.

For women, oestrogen may be taken in the form of the 'combined contraceptive pill' or as 'hormone replacement therapy', depending on your age and whether you need contraception. For men, testosterone can be taken by mouth, in patch or gel form or by injection once a month.

Medication

Medication is a very effective treatment for most prolactinomas. The medication is a type called ‘dopamine agonists’. These act on the pituitary gland to reduce the amount of prolactin it makes, and they can also shrink the tumour. Usually with this medication, prolactin levels go down to normal in a few weeks. Dopamine agonists can be taken as long-term treatment.

The dopamine agonists are called bromocriptine, cabergoline or quinagolide. They are taken as tablets. There are pros and cons of each one - ask your doctor for details.

Are there any side-effects of dopamine agonists?
Possible side effects are nausea, dizziness, constipation, headaches and drowsiness. These are less likely if you start with a low dose and increase gradually. If you feel drowsy, do not drive or use dangerous machinery.

There have been recent concerns that dopamine agonists may cause fibrosis (hardening and damage) of internal organs - if taken in high doses long-term. It is still uncertain how much of a risk there is from these medicines. The research about this dealt with dopamine agonists used in a different situation, to treat Parkinson’s disease, where the doses taken are much higher than for prolactinomas. More details are in the 'Society for Endocrinology' reference below.

What about treatment in pregnancy?
If you are planning a pregnancy, it is best to discuss treatment options with your doctor beforehand. Treating the prolactinoma usually improves fertility, so can help you become pregnant. Bromocriptine is thought to be the safest of the dopamine agonists for pregnancy, because it is the most ‘tried and tested’ one. Many women have had babies after taking bromocriptine.

Discuss with your doctor what to do if you become pregnant. Some women are advised to stop medication during all or part of the pregnancy. Bromocriptine can be used in pregnancy if required.

During pregnancy, some prolactinomas can get bigger. If you have any symptoms such as headache or reduced vision, see a doctor immediately so that this can be checked.

Surgery

Surgery may be an option if medication does not work, is not wanted, or for larger prolactinomas. The operation is called 'trans-sphenoidal surgery', because the surgeon gets to the pituitary through the sphenoid bone, via a small cut above the upper front teeth or from inside a nostril. It is done under general anaesthetic.

Radiotherapy

Radiotherapy (X-ray treatment) focuses high intensity radiation at the prolactinoma, to destroy the abnormal cells. It is not usually needed for prolactinomas - however, it may be used rarely, if other treatments are not sufficient. It can have side-effects.

Other treatments

Sometimes prolactinomas cause a reduction in the other hormones that the pituitary gland produces. If so, you may need to take tablets to replace these hormones. This will depend on your symptoms and blood test results.

What are the complications of prolactinoma, and how are they prevented?

The main complication is the risk of osteoporosis (thinning of the bones), if high prolactin levels are untreated for a long time (over one year). This is because the high prolactin reduces oestrogen or testosterone levels, which can lead to osteoporosis. Osteoporosis can be prevented by treating the prolactinoma (as above), which reduces prolactin levels. Alternatively, replacement oestrogen or testosterone can be taken.

Large prolactinomas may cause complications if they grow and press on the structures nearby: the pituitary gland, the brain and the nerves to the eye. To prevent this, large prolactinomas should usually be treated (see treatment section). If untreated, the pressure might eventually lead to loss of vision, other hormone problems (which could cause severe illness) or severe headaches.

Rare complications are:

• A leak of fluid from around the brain into the nose, which means that there is a risk of infection such as meningitis.
• 'Pituitary apoplexy' is a rare but serious complication, when there is a bleed inside the tumour, making it suddenly expand. This causes sudden increasing symptoms such as headache and reduced vision, and may cause collapse. It needs urgent treatment and may require surgery.
• It is possible, but extremely rare, for a prolactinoma to be malignant (cancerous).

What is the outlook for prolactinoma?

The outlook is very good. Most prolactinomas are successfully treated with medication. If this does not work, surgery is usually successful. Treatment for women can restore periods and fertility (assuming that the fertility problem was due to the prolactinoma). For men also, fertility can improve with treatment, but you may need to take additional medication called 'gonadotrophins' in order to father children.

For some patients, the prolactinoma itself may be cured after about three years of taking medication. So you may be able to come off treatment.

Prolactinomas can recur (come back), even after successful treatment with medication or surgery. You will still need monitoring (such as regular blood tests) to check that the prolactinoma has not come back. If it has, then treatment can be restarted.

Further help and information

Pituitary Foundation
PO Box 1944, Bristol, BS99 2UB
Tel: 0845 450 0375 Web: www.pituitary.org.uk
Support and information for patients with pituitary conditions, including prolactinoma.