|What is it?|
|What causes this?|
|Are these malignant?|
|Do they run in families?|
|How do the patients present?|
|How is the condition diagnosed?|
|What is the treatment?|
|What type of operation is available?|
|What happens at the operation?|
|Will the patient be regularly followed up?|
|What happens if the patient has a malignant phaeochromoctoma?|
|What other therapy is there?|
|What if the phaeochromocytoma lies outside the adrenals?|
What is it?
This a rare condition where the body produces too much of the hormone adrenaline or noradrenaline or both.
What causes this?
The usual cause in 90% of cases is a tumour of the inner core of the adrenal gland known as the adrenal medulla which overproduces both adrenaline and noradrenaline.
However in 10% of cases, the cause is the overproduction of noradrenaline from another source known as the sympathetic nerve chain. This chain comprises a series of nerves with swellings called ganglions or nodules which stretch from the head to the bladder situated along either side of the spine. Normally this nerve chain releases noradrenaline to maintain the bodies proper functioning but in rare cases can become cancerous and overproduce noradrenaline; this is known as ganglioneuroma or sympathoblastoma.
Are these malignant?
90% are benign
10% are multiple found in both adrenal glands but may still be benign
10% are malignant and can spread around the body
Do they run in families?
10% are found in families where other members have a similar condition. There are two major family associations;
1. In those with neurofibromatosis where patients develop lumps along the nerves. This is due to a defective gene.
2. In multiple endocrine neoplasia (MEN type 2). Here the patient may also develop cancer of the thyroid (medullary thyroid carcinoma) and a non-cancerous enlargement and overactivity of the parathyroid glands (hyperparathyroidism) in the neck producing a raised blood calcium. This is once again due to defective gene. In some the gene produces a tall patient with long fingers, thin long face and nose with thick lips and small nodules on the tip of the tongue and lips: called MEN Type 3.
How do the patients present?
The commonest symptoms are as follows;
Often the patients describe sudden onset of attacks with thumping severe headache, profuse sweating and yet look pale, fast heart palpitations, extreme anxiety as if about to die, body tremor, and if measured, a very high blood pressure. After some time (usually less than 15mins but in 80% as long as one hour) the attack subsides and the patient feels washed out. The frequency of attacks can vary from once every 2 months to many times per day but usually become more frequent as time goes by. Between attacks, blood pressure may remain raised but in some reverts to normal. Some 50% of patients exhibit a postural fall in blood pressure even if the supine pressure is normal. The severity of the crises are not dependent on the size of the tumour but on its overactivity; small tumours can be very overactive.
How is the condition diagnosed?
The tests for this condition are as follows;
1. High levels of noradrenaline and/or adrenaline in a 24hour collection of urine.
2. Occasionally blood noradrenaline and/or adrenaline are measured but usually this is not required where urine tests show high levels of these hormones.
3. CAT scan or MRI scan of adrenals show one or both adrenals enlarged. Where the condition is due to sympathetic chain tumour a MRI of the body will pick up the abnormalities.
4. Radioactive labelled meta-iodobenzyl guanidine (MIBG) scan. MIBG is taken up by the cells overactively making noradrenaline / adrenaline. This test is not always successful if the cells concerned are not actually overproducing at the time of the testing.
What is the treatment?
The aim is to surgically remove the tumour(s). However it is essential to first block the action of the excess noradrenaline / adrenaline before the operation. The reason for this is that just the anaesthetic and later handling of the tumour at the time of operation can precipitate a crisis. In a crisis the tumour releases massive amount of hormone resulting in a dangerously high level of blood pressure which could cause a heart attack or brain haemorrhage.To reduce this risk the endocrinologist will arrange for the patient to have the action of noradrenaline / adrenaline blocked by a special drug called phenoxybenzamine. His drug is usually begun in hospital for as it begins to work blood pressure can precipitiously fall requiring expansion of blood volume with salt water given intravenously. The drug dosage will be gradually increased until maximum effect is achieved and this can take many days. For acute attacks the doctor has available an intravenous preparation called phentolamine but this doesnt last long hence the need for the long acting phenoxybenzamine. Once the latter is fully effective then the specialist will add another drug called a beta blocker (usually propanolol) to reduce the force of heart beat and prevent any fast palpitation.
What type of operation is available?
The operation is called an adrenalectomy. This may be of a key hole type but the surgeon may need to do a conventional approach. The latter may involve an incision in your back just below your ribs on one side. If both adrenals have to be removed then this is often done by an incision across the front of the upper abdomen.
What happens at the operation?
While the surgeon removes the phaeochromocytoma your blood pressure, heart rate and output will be monitored by an anaesthetist experienced in this operation. Special extra drugs will be required to control blood pressure etc until the operation is over and the body has restabilised. This may require you to be in intensive care or high dependency care for 24 hours until your cardiovascular system has restabilised. The drugs phenoxybenzamine and propranolol are stopped at the time of the operation.
Will the patient be regularly followed up?
You will be seen by the endocrine specialist life long for regrettably recurrence may occur many years later in possibly 10%. The specialist will repeatedly remeasure your urine noradrenaline and adrenaline.
What happens if the patient has a malignant phaeochromoctoma?
In patients who have malignant phaeochromocytoma there may be a need to continue with the phenoxybenzamine and consider treatment with MIBG loaded with high dose radioactivity. Nevertheless not every patient will find MIBG helpful. Why? Some cells may be malignant that is expanding by growing in numbers but may not actually be oversecreting hormone and therefore not take up the MIBG. Remember MIBG only is taken up by overactive hormone secreting cells.To test for this the specialist will order a MIBG scan once again. This scan will assess those sites which take up MIBG and can therefore be targeted with MIBG loaded with substantial radioactivity. If the scan does show areas of overactivity then MIBG treatment will be ordered but delivered to the patient while in hospital for up to 7 to 10 days. This is necessary for the safety of others for the radioactivity in a treatment dose is very high indeed. The patient has to wait in hospital until the radioactivity has reduced to a level safe for others. Also some 25% can show acute bone marrow suppression and be at risk from infection hence the need for observation of the patient in hospital after the treatment. Prior to MIBG the thyroid is protected by giving iodine but an underactive thyroid can be expected after treatment dosages of MIBG. This is easily treated with thyroid replacement hormone called thyroxine.There is another difficulty with this therapy. As mentioned above MIBG only kills off cells it enters that is cells actively overproducing hormones noradrenaline / adrenaline. If the cell is quiet then MIBG does not enter and is ineffective. Some months or years later these quiet cells become overactive secretors and then can be targeted with MIBG. This is the reason why MIBG scan is repeated at intervals and if areas of old or new activity are seen further courses of MIBG treament may be prescribed. Repeated dosages can eventually suppress the bone marrow.
What other therapy is there?
Some treat malignant phaeochromocytoma with chemotherapy but regrettably this is often not that effective. Bone pain due to tumour invasion may be treated by external radiotherapy. 50% of those with malignant tumour will survive with a good quality of life for at least five years some for considerably longer.
What if the phaeochromocytoma lies outside the adrenals?
In these situations the aim is always to try and remove the tumour by surgical operation but if unsuccessful or just impossible then MIBG treatment is often used as the major therapy.
Ó NHS Tayside; 2006; version 1.0
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