Acromegaly

Understanding the pituitary gland and growth hormone

Location of pituitary gland

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

The amount of growth hormone that you make is partly controlled by other hormones which come from a small part of the brain called the hypothalamus. This is just above the pituitary gland. It makes growth hormone-releasing hormone (GHRH). GHRH tells the pituitary gland to make growth hormone when the level of growth hormone in the blood is low. The hypothalamus also makes a hormone called somatostatin. Somatostatin stops the pituitary gland from making growth hormone when the level of growth hormone in the blood is high.

Growth hormone helps to stimulate growth and repair of various body tissues. It is needed in childhood to help children to grow. Growth hormone acts on some tissues directly. It also stimulates the liver to make another hormone called insulin-like growth factor 1 (IGF-1). Many of the effects of growth hormone are actually due to IGF-1 which acts on various cells in the body.

What is acromegaly and what causes it?

Acromegaly is a condition where you make too much growth hormone. In nearly everyone with acromegaly, the excess hormone comes from a small growth (tumour) in the pituitary gland. This is a non-cancerous (benign) growth called a pituitary adenoma. The adenoma may grow up to 1-2 cm across. However, as it is benign, it does not spread to other parts of the body. The abnormal cells in the adenoma make lots of growth hormone. If the adenoma is very small (less than 1 cm across), it is called a microadenoma. It is not known why the adenoma or microadenoma develops. In rare cases someone who develops acromegaly is related to someone else who has it. When this happens, the cause is genetic. See separate leaflet called Genetic Testing for more information.

Rarely, acromegaly is caused by an excess of GHRH which is made in the hypothalamus. This stimulates the cells in the pituitary gland to make too much growth hormone. Very rarely, other tumours in the body can make growth hormone.

Who develops acromegaly?

Acromegaly is rare. About two to four people in a million develop acromegaly each year in the UK. It mainly develops in adults who are middle-aged (average age 40 years). Men and women are equally affected.

Rarely, it affects children. If it develops in a child (it usually occurs between the ages of 15 to 17 years), it causes the condition called gigantism. This is because growth hormone promotes growth of bones in the body and a child's bones can still grow.

Note: the rest of this leaflet is about acromegaly in adults.

What are the symptoms and problems of acromegaly?

Acromegaly literally means 'enlarged extremities' or 'enlarged hands and feet'. This is a typical feature but there are many other symptoms. The symptoms develop gradually. Some people have symptoms which develop over four to seven years or more before the diagnosis is made.

It is useful to divide the symptoms into two types: those caused by too much growth hormone and those caused by the enlarging tumour (adenoma) in the pituitary gland inside your skull.

Symptoms caused by too much growth hormone

The excess of growth hormone in your bloodstream can affect various tissues in your body which can make them thicken or grow.

So, over time one or more of the following may develop:

• Hands and feet become larger and broader. Your glove and shoe size may increase over the years. You may not be able to get a wedding ring off.
• Your skin may thicken (particularly on the face) and become more greasy and sweaty.
• Changes to your face may include: thickened lips and nose, thickening of your scalp, your jaw becoming more prominent. These changes develop very gradually so may not actually be noticed by your family or friends. However, looking back at old photographs may suggest your facial appearance has changed.
• Your dentist may notice that your teeth are growing apart or that your teeth don't meet properly anymore when you bite your teeth together.
• Your vocal cords thicken which may cause your voice to deepen.
• Your tongue may enlarge so you may often bite your tongue.
• Thickening of cartilage may cause joint pain and arthritis in various joints.
• Thickening of the nasal passages can make you snore loudly and may cause obstruction in airflow when you are asleep (sleep apnoea). This can make you have a poor night's sleep and make you drowsy during the day.
• Carpal tunnel syndrome, where a nerve going through the wrist is squashed by thickened tissue. It can cause pain, tingling and weakness in parts of the hands or arms.
• Irregular or absent periods (in women) may occur.

Other effects of too much growth hormone may include:

• General tiredness.
• Some muscle weakness.
• About half of people with acromegaly also develop diabetes because growth hormone stops insulin from working properly.
• High blood pressure. This develops in about one in three people.
• Increased risk of heart disease and stroke. This is probably because of the increased risk of developing high blood pressure and diabetes.
• People with acromegaly have an increased chance of developing small benign growths (polyps) in the bowel and a slightly increased chance of developing bowel cancer.
• People with acromegaly also have a slightly increased chance of developing thyroid cancer.
• If you have acromegaly you will be offered screening for these conditions (see below).

Also, in about one in three cases, the adenoma also makes too much of another hormone called prolactin. This can cause sexual and menstrual problems and a milky discharge from the nipple. Many men with acromegaly also develop erectile dysfunction (impotence).

Symptoms caused by the growing tumour

In many cases the tumour is very small and does not cause symptoms just by its size. However, in some cases the tumour grows enough to press on the nearby tissues inside the skull. This can lead to:

• Headaches.
• Problems with vision. The tumour may press on the optic nerves (the nerves going from the eyes to the brain) which are just next to the pituitary gland.
• Other normal cells in the pituitary gland may become squashed and damaged. As a result, the pituitary gland may stop being able to produce some other hormones. This can cause an underactive thyroid gland and/or an underactive adrenal gland, which can cause various other symptoms.

How is acromegaly diagnosed?

• A blood test to measure the level of IGF-1 (see above) is measured if acromegaly is suspected. This may also be used as a way of monitoring the disease to see how well treatment is working.
• A blood test can measure the level of growth hormone but this is not a reliable test. This is because the levels of growth hormone in the body fluctuate a lot throughout the day in everybody.
• The diagnosis of acromegaly is made by a glucose tolerance test. In this test you drink a sugar drink containing 75 grams of glucose. You then have a series of blood tests over two hours. The glucose should lower the blood level of growth hormone. However, if you have acromegaly, the growth hormone level remains high.
• A magnetic resonance imaging (MRI) scan can show the size of any tumour.
• Eye and visual tests can assess if the tumour is pressing on the optic nerve.
• If you are confirmed as having acromegaly, other tests will be needed to see if the tumour is causing a lack or excess of other hormones made by the pituitary gland.
• Other tests may include chest X-ray, electrocardiogram (ECG), echocardiogram and CT scan.

What are the treatments for acromegaly?

The aim of treatment is to reduce the amount of growth hormone in the blood back to normal and to reduce the size of an enlarged tumour. Many of the symptoms and features of acromegaly will reverse or improve with successful treatment (apart from any fixed extra bone growth that had occurred).

Surgical treatment

The most common treatment is to remove the adenoma by surgery. This is done using very fine instruments. There are two different ways to operate on the pituitary gland:

The first method is known as endonasal trans-sphenoidal surgery. This involves the surgeon reaching your pituitary gland through a small cut (incision) in the side of one of your nostrils. (Increasingly this is being done using keyhole surgery). In the other way, the surgeon approaches the pituitary gland through a small incision behind your upper lip, just above your front teeth. The instruments are passed through the base of your skull - the sphenoid bone. The aim is to remove the adenoma but to leave the rest of the pituitary gland intact.

The operation is successful, with no further treatment needed, in around nine out of ten cases with smaller tumours. The operation is less successful in those with larger tumours. Sometimes it is just not possible to remove all the cells of the tumour. If not all is removed and your growth hormone level remains high following surgery, other treatments listed below are likely to work.

Your surgeon will advise on the possible complications which can sometimes occur. For example, sometimes the operation may damage some other parts of the pituitary gland. This may cause a reduced production of some other hormones. If this occurs, you will need to take replacement hormone therapy.

Medication

Medication can be used if surgery is not possible, or not wanted. It is also used when surgery fails to remove the tumour totally and the level of growth hormone remains high.

• Somatostatin analogues (octreotide and lanreotide) reduce the level of growth hormone to normal in over half of cases and reduce the size of the tumour in about eight in ten cases. However, these medicines need to be given as an injection. They work in a similar way to somatostatin (described above) which is a hormone that prevents growth hormone from being released from pituitary cells. These medicines used to be injected several times a day. However, longer-acting preparations are now available as monthly or fortnightly injections. Side-effects are usually mild with these medicines. Some people develop tummy (abdominal) pains and diarrhoea but these usually wear off with time. Gallstones can also occur but rarely cause problems.
• Dopamine agonists (such as cabergoline, bromocriptine and quinagolide) can be taken as tablets. They work by preventing the release of growth hormone from tumour cells. They work well in about one in five cases. Side-effects such as feeling sick and dizzy are also quite common.
• Pegvisomant (Somavert®) is taken as a daily injection. However, unlike the other medicines listed above, it does not act directly on the pituitary gland. Pegvisomant works by blocking the action of growth hormone on your body's cells. Therefore, although many of the symptoms of growth hormone excess will be eased, it does not reduce the size of the adenoma and so any headaches are not eased.

Radiotherapy

Radiotherapy is an option to reduce the size of the tumour and hence reduce the production of growth hormone. Radiotherapy focuses high-intensity radiation at your pituitary tumour to destroy the abnormal cells. It may be used if you are not able to have surgery. However, it can take months or years after the radiotherapy is given for the level of growth hormone to reduce to normal. You can take medication whilst waiting for the effects of radiotherapy to work.

A possible side-effect of pituitary radiotherapy is damage to other normal pituitary cells. This can cause a reduced level of some other hormones. However, if this occurs you can take replacement hormone therapy.

Acromegaly and cancer screening

As mentioned earlier, people with acromegaly have an increased chance of developing small benign growths (polyps) in the bowel and bowel cancer. Therefore, if you are diagnosed with acromegaly and are aged 40 years or more, you will normally be offered a routine colonoscopy every three to five years (You may only be offered one every ten years if your hormone levels are always normal.) A colonoscopy is a test where an operator - a doctor or nurse - looks into your large bowel (colon) with a flexible telescope. It can diagnose bowel problems such as polyps and bowel cancer. The aim is to detect those people who develop cancer as early as possible (before symptoms develop) when the chance of a complete cure is high.

However, you should always tell your doctor if you develop any new symptoms from your bowel, such as persistent diarrhoea, passing mucus, passing blood, or tummy (abdominal) pain.

People with acromegaly also have an increased chance of developing thyroid cancer. The thyroid is a small gland in the front of your neck. Your doctor will want to examine your thyroid gland every so often and may arrange for you to have an ultrasound scan of your neck if you have developed any lumps in your thyroid.

Acromgealy is not linked to any other cancers, such as breast cancer or prostate cancer.