Acromegaly is a condition of the overgrowth of tissue caused by prolonged excessive production of growth hormone (GH) occurring after normal skeletal growth has ceased. The high levels of GH stimulate the liver to secrete insulin-like growth factor-1 (IGF-1), which causes most of the signs of acromegaly.
It is a slowly progressive, rare condition, found in three to four persons per million per year. It affects young adults mainly, and can cause much disfigurement due to enlargement of the face, jaw, hands, feet and skull. Untreated, the condition can lead to serious illness (for instance, diabetes, heart disease) or even death.
Nearly all cases are due to a small benign tumour of the pituitary gland – an adenoma – situated in the middle of the head, just below the brain. The tumour secretes excess amounts of GH. There is much variation in the rate of growth of these adenomas, and in the amount of GH they secrete.
Younger patients generally have more aggressive tumours. In addition, the adenoma itself may compress some of the normal pituitary tissue around it: this tissue may thus be prevented from secreting its normal hormones (for example, sex hormones), causing specific deficiency states (such as impotency in men). The tumour can also compress part of the optic nerve, causing specific visual loss.
Some patients have other tumours, for instance in the pancreas, lung or adrenal glands, which produce a substance (GHRH) which stimulates a normal pituitary gland to keep producing GH.
Symptoms and complications
Symptoms are due to a combination of tissue overgrowth and the effects of GH on organs and metabolism, and include:
- Coarsely enlarged hands, feet, face, jaw, lips, tongue and fingers, with thickened skin;
- Joint pain and decreased joint mobility, carpal tunnel syndrome;
- Muscle weakness, with easy fatigueability; and
Headache, hoarseness and excessive sweating and sebum production.
Complications in untreated patients can include
- Hypertension and heart failure;
- Diabetes mellitus; and
- Kidney failure
Investigations and diagnosis
While the clinical picture is clear, confirmatory tests must be done to avoid inappropriate or hazardous treatment.
Measuring GH is possible, but, because GH levels vary from hour to hour (affected by sleep, exercise and food), this may be misleading. The best single diagnostic test is measurement of serum IGF-1, whose secretion is steadier. This must be considered together with GH values, and other findings. An oral glucose tolerance test may also contribute.
Once biochemical tests confirm the diagnosis, the source of the excess GH must be determined. The vast majority of patients have a pituitary adenoma, which can be shown up by an MRI scan, even though they can be as small as 2mm. If the MRI does not show a tumour, then chest and abdominal studies must be done to search for a tumour there. Also, serum GHRH can be measured: high levels with a normal-looking pituitary suggest a source elsewhere in the body
Treatment and outcome
Treatment aims to normalise the levels of GH and IGF-1 to age and gender appropriate levels, without causing an under-reactive pituitary gland. This returns the life expectancy to normal.
Surgery is the treatment of choice, especially if there are visual problems. In very large tumours, surgery may be used to remove as much tumour as possible so that the small amount left behind can be treated by other means. In experienced hands, surgery is highly successful: it normalises the IGF-1 levels, has a very low recurrence rate and only rarely causes hypopituitarism. Some highly specialised surgeons can now do this procedure working through the nose using an endoscope, with excellent results.
Complications of surgery can include spinal fluid leak, diabetes insipidus, and meningitis.
Medical treatment is indicated in patients whose surgical risk is too high, or as post-operative additional therapy. Octreotide, lanreotide, cabergoline, bromocriptine and pegvisomant are some of the drugs used. Their success rate is about half that of surgery, but they can help to shrink the tumour somewhat.
Radiotherapy can be used for tumours uncontrolled by surgery or medical means. Tumour shrinkage is good, but there is a high incidence of abnormal pituitary function afterwards.
(Dr AG Hall, Health24, January 2008)