Acromegaly

 

What is Acromegaly?

Acromegaly is a rare condition causes by an excess of Growth Hormone (GH) during adulthood. GH is produced in a gland called the pituitary gland at the base of the brain in response to a growth hormone releasing hormone (GHRH) produced by the hypothalamus which a small part of the underside of the brain. In childhood, GH levels in the blood are largely responsible for the degree of growth of that person. Therefore, too little GH in childhood is likely to result in someone who is short (and is even one cause of dwarfism) whereas too much can result in a condition called 'gigantism' where the individual grows abnormally high.

However, if there is too much GH activity in an adult who has already achieved their natural height, it results in abnormal enlargement of certain tissues of the body and certain parts of the skeleton.

Who gets Acromegaly?

Acromegaly is rare, occurring in only 3-4 per million people per year and generally occurs in adults between the ages of 30-50 and affects men and women equally.

Why does it occur?

The most common cause of acromegaly is the excessive production of GH from a small tumour on the pituitary gland called a 'pituitary adenoma' which may increase in size to 1 or 2 cm across. It is not known why the adenoma arises but its existence in the very confined space at the base of the brain can cause pressure effects on the surrounding nerves (see below). Far less commonly, it is caused by too much GHRH being produced by the hypothalamus which therefore results in excessive production of GH by the pituitary gland. Even more rarely, other tumours in the body can produce their own GH leading to acromegaly.

 

One of the problems of diagnosing Acromegaly is that the symptoms can occur very slowly over a matter of many years but generally they fall into those symptoms caused by the pituitary tumour (if this is the cause) and those symptoms resulting from the effect of an excess of GH.

Symptoms due to the existence of the tumour include persistent headaches and visual defects, particularly tunnel vision, as a result of pressure of the tumour on the optic nerve. Also, pressure on the pituitary gland may cause underactivity of other parts of the gland sometimes causing reduced levels of thyroid hormone or adrenal hormones as a knock-on effect.

Symptoms due to an excess of GH include:

  • An increase in size of hands and feet.
  • Thickening of the skin especially on the face and the skin may become greasy.
  • Changes in facial appearance especially thickening of the nose, the lips and prominence of the jaw.
  • Thickening of the vocal cords leading to deepening of the voice and enlargement of the tongue which may result in the person speaking with a lisp and constantly biting their tongue.
  • Changes in the tissues of the wrist may cause something called 'Carpal Tunnel Syndrome' where the nerve going through the wrist becomes compressed resulting in pain and numbness of the hand.

Other more generalised symptoms may occur including:

  • Muscle weakness and lethargy.
  • An increased risk of developing diabetes because GH counteracts the effects of the sugar-lowering hormone insulin.
  • A 1 in 3 chance of developing high blood pressure.
  • These last two combine to increase the chances of the person suffering from a heart attack or stroke.
  • Strangely, people with acromegaly also have a greater chance of developing bowel cancer as a result of developing polyps in the bowel.
  • The heart, liver and kidneys may also increase in size.
 

A doctor may suspect the diagnosis from the history of the changes in appearance listed above but proof involves performing certain blood tests. Measurement of GH does not necessarily show an increased level in the blood so a more accurate measurement of the active form of GH called IGF-I may show an increase in this hormone.

In addition a test called a Glucose Tolerance Test is done where the individual fasts overnight and then has blood tests done before consuming a measured dose of glucose and then repeating the blood tests. In people without acromegaly, their blood levels of GH drop after consuming the glucose whereas acromegalics do not demonstrate this reduction in level.

Visual field tests may show a type of tunnel vision called homonymous hemianopia and a CT or MRI scan of the brain is usually done to look for the presence of a pituitary adenoma.

How is Acromegaly treated?

The aim of treatment is to reduce the level of GH to normal and relieve the pressure that the pituitary adenoma (if it is present) has on the surrounding tissues thereby reversing the symptoms caused by these 2 factors. There are various ways of achieving these aims and sometimes more that one method of treatment is used.

Surgery

The most common form of treatment is surgery to remove pituitary adenoma. This is specialised surgery since it involves exposing the pituitary gland by going through the nasal passages or into the skull via an incision through the inside of the upper lip. If it is not possible to completely remove the adenoma, other treatments are needed to further reduce the level of GH. Also if some of the normal pituitary gland is unintentionally removed, the individual may need to replace the resulting reduced level of hormones such as thyroid hormone.

Radiotherapy

Sometimes radiotherapy is used to shrink the pituitary tumour either on its own or as a lead up to surgery to make the tumour easier to remove. The reduction in GH levels as a result of radiotherapy may take several years before its full effect has taken place so it is usually used in combination with other treatments such as surgery and/or medication.

Medication

Medication is sometimes used on its own if surgery is not a possibility for one reason or another or can be prescribed in combination with surgery or whilst waiting for the effect of radiotherapy to fully work which, as mentioned above, may take several years to have its full effect.

Medication options include:

  • Somatostatin analogue drugs such as one called Octreotide or another called Lanreotide which reduce the level of growth hormone to normal in over half of individuals with Acromegaly by inhibiting the release of GH from the pituitary gland. They also have the advantage that in 30% of cases they shrink the pituitary tumour responsible for the condition. They are given as monthly or fortnightly injections.
  • Another type of medication called Dopamine antagonists such as one called carboline are taken orally and work by preventing the release of GH from the tumour. Unfortunately they only work in a minority of cases.
  • A new drug called Pegvisomant is a daily injection which does not reduce the level of GH but does block the effect of GH on the tissues of the body. As a result, it treats the symptoms associated with an increased level of GH but does not in any way shrink the pituitary tumour so is not effective in reducing the symptoms associated with pressure from the tumour on neighbouring tissues (see above).