Prolactinoma

Prolactinoma

Where they are secreted from and what they do
The pituitary gland
The pituitary gland produces a number of hormones, including: prolactin, ACTH, TSH and GH, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Prolactin is sometimes known as the ‘milk hormone’ because it stimulates milk production after childbirth, but it is also produced in men, although in smaller amounts. FSH and LH control sex and reproduction. In women they cause release of the sex hormone oestrogen and stimulate the ovaries to produce eggs; these hormones are essential for a normal menstrual cycle. In men, they cause the release of testosterone and stimulate production of sperm from the testicles. The pituitary & hypothalamus Cerebellum Brain Stem Pituitary Cerebrum Hypothalamus

What causes the Prolactin level to be raised?

Common causes of raised prolactin
•Pregnancy
•Nipple stimulation and suckling
•Stress
•Certain medications such as:
■ Anti sickness medications e.g. Metoclopramide, stemetil, Domperidone, also acid reducing medication like Omeprazole can raise your prolactin level.
■ Certain antidepressants and tranquillisers used to treat mental health illness can raise prolactin: examples include Amytriptyline and Fluoxetine (Prozac) and risperidone.
■ Some homeopathic and herbal medications.
Another possibility of raised prolactin is an underactive thyroid gland, which can be diagnosed by a simple blood test and which requires treatment with thyroid hormone tablets. Once your doctor has excluded these causes, he or she will consider the possibility of a prolactinoma.

Make sure you tell your doctor about all your current prescribed and any non-prescription medication you are taking.

What is a Prolactinoma?
A prolactinoma is a prolactin-producing tumour of the pituitary gland. Please be assured that this is a benign tumour, and not a brain tumour or cancer.

Doctors use the words ‘tumour’, ‘adenoma’ or ‘growth’ which means a swelling on the pituitary gland. These tumours only grow very slowly and many do not seem to grow at all. We do not know exactly what causes prolactinomas, but they are the most common type of hormone-producing pituitary tumour.

The action and stress of performing a blood test can mildly elevate the prolactin level and for this reason more than one level requires to be checked.

An appointment with an endocrinologist is usually sought by the GP, when there have been repeated raised levels of prolactin. Following referral to an endocrine department, the initial appointment will probably entail having your prolactin level re-checked.

Prolactinomas come in various sizes, but the vast majority are less than 10mm (3/8 inch) in diameter. These are called microprolactinomas. The rarer, large tumours greater than 10 mm in size are called macroprolactinomas. Prolactinomas can occur in men and women. The symptoms produced by a prolactinoma depend on the sex of the patient and the size of the tumour.

Signs and symptoms of a Prolactinoma
Signs and symptoms presenting in women
Most women with prolactinomas are likely to have microprolactinomas. Your first symptoms may relate to loss of periods (amenorrhoea) as excessive prolactin interferes with the pituitary’s production of the hormones FSH and LH which control the menstrual cycle. You may have reduced interest in sex (low libido) and experience vaginal dryness and discomfort during intercourse. You may also be infertile because of impaired egg release by the ovaries - as we shall see later, there is usually effective treatment for this problem. You may also develop excess breast milk production (called galactorrhoea), which may leak spontaneously. This is due simply to the biological action of prolactin and is not a sign of breast disease, particularly breast cancer. Women with prolactinomas do not have any increased risk of breast cancer.

NB: If galactorrhoea is a symptom: it is important to note that self examination and expressing of milk acts as stimulation and therefore reinforces the raised prolactin level, making galactorrhoea persist! Although it is tempting to look to see if it is still present, you should resist the temptation.

Signs and symptoms presenting in men
Men with prolactinomas usually have tumours larger than 10mm in diameter (macroprolactinomas). However, a larger size tumour does not rule out an excellent response to tablet treatment. As in women, excessive prolactin reduces production of FSH and LH by the pituitary gland. This in turn lowers testosterone levels and may result in a reduced interest in sex (low libido) and in impotence. Men may also have infertility due to a low sperm count. Milk production by the male breast can occur but is very uncommon even when prolactin levels are very high.

Once diagnosed and treatment with medication has been established and the abnormal level of prolactin starts to decrease, the abnormally low testosterone level should in turn start to recover and rise again. This does not happen in all cases and in that instance the men will go on to have hormone replacement therapy in the form of testosterone.

Large tumours
If you have a large tumour, you may have pressure symptoms such as headache or visual problems. This is because the nerves to your eyes pass over the top of the pituitary gland. In a minority of patients, an increase in pituitary size may cause pressure on these nerves and produce visual disturbance. Again, even these prolactinomas can usually be treated effectively with tablets, rather than surgery.

Diagnosis and what tests are carried out?
How is a Prolactinoma diagnosed?
The tests to diagnose a prolactinoma are relatively straightforward and should not cause you too many problems. They consist of blood tests to check hormone levels and a scan of the pituitary gland to show the size of the prolactinoma. As mentioned previously, stress and the insertion of a needle to take a blood sample can slightly raise your prolactin level, so it requires to be repeated more than once to ensure the result is consistently high and a true value. Another cause of raised prolactin can be a benign condition called macroprolactinaemia, which is an artefactual elevation of serum prolactin measurement, as a result of prolactin with certain blood proteins. It is of no clinical significance but must be distinguished from prolactin-producing pituitary tumours.

Your GP may carry out initial tests on your prolactin and thyroid levels. You then would need to attend a specialist endocrine clinic as an outpatient for further tests, including any scans (see below).

As mentioned previously, a further blood sample will be taken to make sure your thyroid gland is functioning normally. The other hormones produced by the pituitary will also need to be checked; this can be done by a single blood sample.

Some specialists may recommend further tests to better assess pituitary gland function. These will be explained to you should you fall into this category. Mostly these investigations involve timed blood sampling and possible administration of a hormone or specific drug to produce stimulation or suppression.

A scan is usually carried out to give detailed pictures of the pituitary gland. There are two types of scan:
• MRI (magnetic resonance imaging, using a special magnetic technique)
• CT or CAT (computerised tomography, using X-ray imaging)

MRI is the scan of choice. Both types of scan involve you lying on a moveable table and passing into a cylindrical piece of equipment. You may find the examination a bit noisy or claustrophobic, but you will probably find that it does not give you too much trouble. If you feel it might cause you concern, ask your GP beforehand if you can have a sedative to take. During the scan, the radiologist may inject a special dye into your arm so that your prolactinoma can be seen more clearly.

A minority of patients are allergic to this injection, so do tell the specialist if you have asthma or any allergies.

 If you have any problems with your vision, you will probably be seen by an eye specialist (opthalmologist) who will check the strength of your eyesight and chart your fields of vision. Sometimes an X-ray scan of your spine and hip bones (bone densitrometry) may be recommended to see whether there is any evidence of thinning of the bones (osteoporosis). This is a painless and straightforward test commonly called a DEXA scan.

Women who have not had periods for a year, and male patients with prolonged low testosterone levels should be offered bone density tests to ensure that they are not developing osteoporosis.

How is a Prolactinoma treated?
Medication treatment
Whatever the size of your prolactinoma, it is likely that your treatment will be with tablets. Drugs known as dopamine agonists are the first line medication in patients presenting with a prolactinoma. Cabergoline (brand name - Dostinex), Bromocriptine (brand name - Parlodel) and a third drug, Quinagolide (brand name - Norprolac) are the three available medications. All these drugs act by reducing prolactin secretion by the prolactinoma.

• Cabergoline is long acting and requires one or two doses per week. The usual dose of cabergoline is one tablet (0.5mg) once or twice a week, although higher doses are occasionally required. Sometimes the dose can be reduced later during long-term treatment.

• Bromocriptine is usually given twice or three times daily (one tablet 2.5mg)

• Quinagolide is taken once daily, with the dose increased gradually to 75micrograms.

These drugs are safe and well tolerated by most patients. To minimise any side effects, particularly dizziness on standing up, nausea and headaches they should be taken with food. Cabergoline should to be taken at night when going to bed with a light supper or snack e.g., tea/milk and a biscuit. This should reduce the chance of any unwanted effects.

Your doctor will give you instructions on how to build up the dose slowly, again to minimise any side effects, particularly dizziness on standing up and headaches. Generally these side effects will diminish as your body becomes used to the medication but should they persist or become unbearable please discuss with your consultant or endocrine nurse specialist at your endocrine clinic. Occasionally, the medications may cause slight constipation, but this can usually be cured by increasing the amount of fibre in your diet. Other side effects include tiredness, abdominal pain, breast discomfort and nasal congestion. Psychological disturbance may be a rare complication of either cabergoline or bromocriptine.

Dopamine agonists
Recent findings in patients with Parkinson’s disease using dopamine agonists in large doses (often at least 20 times those used for prolactinoma treatment) have shown some heart valve problems, however, there is no evidence that this occurs in patients with prolactinoma on the lower doses of cabergoline which are generally used in this condition. Patients taking Cabergoline or Bromocriptine for pituitary conditions will be advised to have occasional echocardiograms (heart scans) as a precaution. Your endocrinologist or GP will arrange this for you.

Prolactin levels often fall to normal within a few weeks of starting the treatment. In women, once prolactin has fallen to normal, menstrual cycles usually resume; interest in sex is regained and fertility is restored in most cases. In men, testosterone levels may raise, which often improves sex drive and potency.

Nearly all prolactinomas shrink in size following treatment with the tablets. If your prolactinoma is pressing on the nerves to the eyes, there is a good chance that your vision will improve as the tumour shrinks. If you have a large prolactinoma, you may have several pituitary scans over the months and years so that the shrinkage can be assessed.

Pregnancy
Fertility may return quite quickly, so if you do not wish to become pregnant, you and your doctor will need to discuss an effective method of contraception, before medication is started. If pregnancy is wished, it is advisable to see your endocrinologist for pre-pregnancy planning and advice. Once pregnancy is established, most patients are recommended to discontinue medication but you should seek advice from your endocrinologist. You will continue to be seen by your endocrinologist throughout your pregnancy, to monitor progress. Checking blood levels of prolactin during pregnancy is unhelpful since they rise during a normal pregnancy. There is good safety data for babies conceived whilst the mother is taking dopamine agonists.

Breast feeding
If you wish to breast feed you should discuss this with your endocrinologist during your pregnancy. Following the birth you will be reassessed by your endocrinologist regarding the need for further treatment for your Prolactinoma.

Surgical treatment
The use of surgery and radiotherapy for prolactinomas has declined in recent years, due to the remarkable effectiveness of tablet treatment. Very few patients with microprolactinomas will require these treatments, although some hospitals may offer surgery as an option - most commonly for patients who are resistant to the drugs (5%) or suffer side-effects (5%). For the minority of patients with macroprolactinoma, which do not shrink following medical treatment (less than 10%), surgery may be required, particularly if 10 Prolactinoma How is a Prolactinoma treated? your vision has not improved. However, what was previously a big operation has now been greatly simplified by a more minor procedure through the air sinuses at the back of the nose. This is known as trans-sphenoidal surgery, which uses an operating microscope and there is now endoscopic trans-sphenoidal surgery, the same surgery performed using an endoscope, an option which may be available in your area. Please see our Surgery and Radiotherapy Booklet.

If a large prolactinoma does shrink effectively following tablet treatment, most specialists simply continue the drug, but perhaps in a reduced dose. General pituitary function may improve after tumour shrinkage has occurred.

However, if you continue to have pituitary under-activity following treatment of your prolactinoma, then hormone supplements may be required. These may include steroid tablets for adrenal under-activity, thyroid hormone tablets for thyroid under-activity and possibly, oestrogen HRT for women or testosterone supplements for men. Growth hormone replacement therapy may also be required. Please see The Pituitary Gland; Its Conditions and Hormones Explained Booklet.

If you notice any clear watery fluid coming from one or both nostrils, report this immediately to your doctor, just in case it might be leakage of CSF (cerebrospinal fluid which surrounds the brain).