Professor Richard Ross
University of Sheffield

Acromegaly is caused by an excessive amount of Growth hormone (GH) being released, usually from a tumour of the Pituitary gland. This is an isolated event and familial acromegaly (where it occurs in families) is very rare. The genetic causes of pituitary tumours are not known. Acromegaly is most common in adults between 30 and 60 years of age. Pituitary tumours are very rare in childhood, but occasionally acromegaly can occur before growth has stopped, resulting in a condition called Gigantism. This occurs because the Pituitary tumour causes delayed fusion of the epiphyses (ends of long bones), which continue to grow due to the high levels of GH from the tumour.

The name "acromegaly" literally means "enlargement of the extremities or hands and feet" and this is the cardinal feature of the condition. Other features include excessive sweating, facial changes, including protrusion of the jaw, skin thickening and high blood pressure. Heart disease is increased, possibly because of the association of high blood pressure and diabetes, which is seen in some patients with acromegaly. A third of patients with acromegaly have high Prolactin levels. The risk of bowel cancer may be increased and it is generally felt that this is increased about two-fold in patients over the age of 50. In such patients colonoscopy may be advisable.

There are three main series of symptoms that can occur as a result of acromegaly. One is due to the effect of the high levels of GH, which cause the above effects. The second is due to the fact that there is a tumour, albeit a benign (non-cancerous) one, which interferes with normal pituitary function so that underactivity of the pituitary can occur in relationship to the Gonads (the testes and ovaries), the thyroid and the Adrenal glands. The third main series of symptoms is related to the fact that the tumour is occupying a space near the eye nerves and the bottom of the brain, causing visual problems and headaches caused by the expansion inside the head of the pituitary gland.

Acromegaly is treated using three main methods: surgery, medical treatment with drugs and external beam Radiotherapy. With surgery, 50% of patients can be expected to be cured of acromegaly. As GH from the pituitary stimulates the production of Insulin-like Growth Factor-1 (IGF-1), and it is this substance that causes the problems in acromegaly, treatment aims to reduce growth hormone levels to 5 mU/l and IGF-1 levels to within the normal range.

Medical treatment currently involves two main groups of drugs. Dopamine agonists (cabergoline, Bromocriptine and quinagolide) are easiest because they can be taken orally. Unfortunately they only work in 15-20% of patients and it is not often possible to gain control of acromegaly after surgery has not had optimal results. Somatostatin analogues (Octreotide and Lanreotide) act on the pituitary to decrease GH levels. These drugs control the high levels of growth hormone in 50-60% of patients and in otherwise untreated patients pituitary tumour size decreases in about 80% of cases. Somatostatin analogues may also be effective for treating headaches. Thrice daily injections have been superseded by two main preparations: Sandostatin LAR (octreotide), which is given by injection every month and costs about £10,000 a year and Somatuline Autogel (lanreotide), which is given every month and is slightly less expensive. Occasionally gastrointestinal side effects of colicky abdominal pain and diarrhoea can occur but these usually wear off with time and are less frequent with the long-acting compounds and with the subcutaneous injections. Gallstones can also occur but rarely cause problems.

A treatment soon to be available involves a drug that is administered by daily Subcutaneous injection. The drug, called Somavert (pegvisomant), has just received the approval of the European Licensing Agency and should be available next year. Pegvisomant antagonises GH and so does not act directly at the pituitary but simply blocks the action of GH. This drug has been shown to reduce IGF-1 levels in over 95% of patients and overall it is the most effective method of reducing IGF-1 levels to normal using only medical treatment. Few side effects are recorded but the size of the pituitary gland needs to be monitored during treatment.

Lastly, external radiotherapy can be given to reduce the size of the tumour and hence reduce GH production. This is effective but takes time to work and can adversely affect other pituitary functions, so hormone replacement therapy becomes necessary.