Professor R N Clayton
North Staffordshire Royal Infirmary

Acromegaly is a rare disorder. About 4-6 new cases per million of the population are diagnosed each year. The peak age of presentation is 30-60 years old. Acromegaly is almost always caused by a Pituitary tumour (very rarely, other tumours can secrete Growth hormone). 70% of the tumours are larger than 1 cm (macroadenomas) and 30% are smaller than 1 cm (microadenomas). Generally speaking, successful surgery is more likely if the tumour is smaller (larger tumours tend to give rise to higher GH levels).

Patients with acromegaly have often had the condition for several years before a diagnosis is made. The diagnosis is often suggested by healthcare professionals who have not seen the person for some time, as they appreciate the change in appearance more than those who see the person every day.

The symptoms of active acromegaly (apart from change in appearance) include sweating, Carpal Tunnel Syndrome (pins and needles in the fingers), headaches and visual problems. Other problems associated with acromegaly include high blood pressure, diabetes and reduction in other pituitary hormones (often causing tiredness, weight gain and menstrual/sexual dysfunction).

The diagnosis of acromegaly is made by a glucose tolerance test (a 75 gram glucose load is drunk followed by a series of blood tests over two hours). A high intake of glucose should lower GH levels i normal individuals, but in acromegaly GH remains high. A MRI (or CT) scan is performed to determine the size of the tumour. Generally, MRI is better than CT, but the MRI scanner can cause claustrophobia. Visual field testing may also be performed, as the Pituitary gland sits near the optic chiasm (important for field of vision).

Untreated acromegaly is associated with increased risk of dying from heart problems, stroke and lung problems. Overall acromegaly has approximately double the mortality rate in the UK. The risk of complications is increased with higher pre-operative GH levels, high blood pressure, heart problems and increased length of time before diagnosis.

The aim in the UK is to lower GH levels to below 5 mU/l. Some people use the figure 2.5 ng/dl but note that this is the equivalent value in different units (figures in mU/l are higher than the equivalent in ng/dl). This figure is based on long-term studies, but some people think we should be aiming for even lower than 5 mU/l. IGF-1 (Insulin-like Growth Factor-1) is a chemical produced by the liver in response to GH. It is a good marker of GH activity over several weeks and the aim is to normalise this with treatment. IGF-1 has a normal range that is related to patients' age.

Transphenoidal hypophysectomy (removal of the pituitary gland via the nose) is the treatment of choice, if the patient is fit enough for an operation. An experienced pituitary surgeon, who does this operation all the time, should perform the surgery. If the post-operative GH level is less than 5 mU/l, there is a very good chance that the problem will not recur and no further treatment will be required apart from surveillance. If GH is greater than 10 mU/l, further treatment is almost certainly needed. If the GH is between 5 and 10 mU/l, the decision to do anything else is less clear-cut and depends upon symptoms and doctor and patient preference.

If surgery alone does not bring the GH level down sufficiently (this is not uncommon as often the tumour is near to the carotid artery and would lead to a stroke if the surgeon tried to remove it), medical treatments or Radiotherapy are available to further lower GH. The medical treatments include dopamine agonists and Somatostatin analogues.

Dopamine agonists include Bromocriptine, cabergoline and quinagolide. These may give rise to side-effects such as nausea and dizziness. Many patients report increased emotional problems on these tablets.

Somatostatin analogues include Octreotide (Sandostatin and Sandostatin LAR) and Lanreotide (Somatuline LA). These are only available by injection. Octreotide is available as a Subcutaneous injection (three times a day) or a slow release Intramuscular injection (once a month). It may be possible to arrange a six weekly injection if your Endocrinologist is in agreement. Lanreotide is an intramuscular injection given every 7-14 days. The somatostatin analogues are good at lowering GH levels as well as improving the unpleasant symptoms of active acromegaly. Some patients prefer one form of injection to another, depending on tolerability of injection and specific symptom control e.g. patients with severe headache may prefer to be on the short acting octreotide injections for this symptom. The side-effects of somatostatin analogues include abdominal bloating and diarrhoea, which tend to improve. Long-term use may give rise to gall stones.

Radiotherapy is a useful adjunct to surgery and medical treatment. The response may take several months and often leads to hypopituitarism, requiring long-term hormone replacement. A new form of radiotherapy, called 'gamma-knife', exists that concentrates the X-rays in a smaller area. The hope is that it will cause less hypopituitarism.

A new treatment for acromegaly will be available later in the year. Early results are very promising. The drug is a GH receptor antagonist, called pegvisomant (Somavert). It is well tolerated and lowers IGF-1 impressively. It is good for all the symptoms of acromegaly apart from headache. The only slight concern is that rather than reducing GH levels, it blocks its actions, so GH levels remain the same (or higher). No one knows whether this can give rise to problems. Generally it is considered to be an excellent new adjunctive medical therapy for acromegaly.