Treatment of Phaeochromocytoma

Fig.1: Dr Charles MayoSurgical excision of phaeochromocytoma is the treatment of choice, and for non-malignant tumours the 5-year survival rate is 95%. The first successful removal of a phaeochromocytoma was almost 75 years ago in 1926 by Dr Charles Mayo. (Fig. 1)  The operation is complicated by the dangers of both hypertension and hypotension, and must be performed by an experienced surgeon with expert anaesthesia.

Preoperative preparation

There is no effective medical treatment, but adrenalectomy should not be undertaken without adequate preparation of the patient. The introduction of alpha-adrenergic blockade has reduced the perioperative mortality from 13-45% down to 0-3%.

Blood pressure should be controlled for 10-14 days prior to surgery, usually with phenoxybenzamine, starting at a dose of 20-60mg per day in divided doses. This is increased gradually until hypertension is controlled, postural hypotension becomes a problem or the maximum dose of 160mg per day is reached. Patients (and their doctors) know when they are fully 'blocked', and safe for surgery, when they develop a stuffy nose, and feel dizzy when standing up, which are the side effects of the drug.

If tachycardia becomes a problem, then beta-blockade can be introduced, but only after adequate alpha-blockade has been achieved. Beta-blockade is often not necessary however, and may mask incomplete alpha blockade resulting in critical intra-operative increases in systolic blood pressure.

Prazosin or Doxazosin (calcium channel blockers and selective alpha-1 antagonists) can also be used to block patients prior to surgery if phenoxybenzamine is not tolerated.

However, even the use of alpha blockade at all prior to surgery is now controversial, with several centres now no longer insisting on it before minimally invasive adrenalectomy is undertaken. Most anaesthetists who deal with this problem infrequently however, will insist on adequate blockade beforehand, and this is probably the safest option in most cases.

Adrenal surgery

Specialist anaesthesia

Excellent and highly-skilled anaesthetic care  is required, with maximal haemodynamic monitoring  and resuscitation available. During the operation the patient must have central venous pressure monitoring and intra-arterial blood pressure monitoring. 

Great caution should be taken when using drugs that may evoke a hypertensive (pressor) response. A list of these drugs is shown below:

• Drugs that induce histamine release (e.g. morphine)
• Drugs that interact with catecholamines
• Sympathomimetic agents
• Indirectly acting sympathomimetic agents

Surgery

Fig.2: Laparoscopic adrenalectomyThe adrenalectomy can generally be achieved by laparoscopic (keyhole) surgery (Fig. 2), except in the case of very large tumours or those suspected to be malignant, when open operation is safer. In fact laparoscopic operation is probably safer than open surgery for phaeochromocytoma (Fig. 3) as there tends to be much less manipulation of the gland prior to clipping of the adrenal vein.

To avoid the release of any catecholamines into the systemic circulation, the priority of the surgeon is to isolate the adrenal vein with as little manipulation of the gland as possible, to prevent release of a massive dose of catecholamines into the bloodstream and precipitation of a hypertensive crisis.

Fig.3: Phaeochromocytoma in the centre of the adrenalectomy specimenExcellent communication between the anaesthetist and surgeon is needed to prevent sudden changes in blood pressure, either up (with gland manipulation) or down (after clamping of the adrenal vein).

As a result of surgery 75% can expect a normalisation of blood pressure, with the remission of hypertensive paroxysms.

If the tumour is malignant and metastases are present then ¹²³I-MIBG is used to visualise any additional tumours. Elevated catecholamine levels in the urine may also confirm their presence postoperatively.

In the case of malignant tumours the 5-year survival rate is 44%. It may prove too difficult to locate and remove all metastases, so medical therapy and radiotherapy are used. Alpha- and beta-blockers may be used, but the tyrosine hydroxylase inhibitor alpha-methylparatyrosine is more powerful in controlling symptoms. ¹³¹I-MIBG is used to treat the tumours, as it is selectively taken up and has proven effective in shrinking the metastatic tumours and helping catecholamine levels return to normal. The recommended dose of 5550MBq can be given safely up to a limit of 33750Mbq in total.

Although surgery has a high success rate, all patients should attend annual follow up appointments to have urinary catecholamine levels checked so that any further tumours may be detected.

Phaeochromocytoma in pregnancy 

The combination of phaeochromocytoma and pregnancy (estimated to occur in 1 in 54,000 pregnancies) can be lethal for both mother and baby. It is usually diagnosed when the mother is noted to be hypertensive during antenatal care, confirmed by plasma metanephrines, urinary catecholamines and MRI scanning (which is safe in pregnant women). CT and MIBG scanning is not possible during pregnancy.

Alpha blockade with phenoxybenzamine can be given and successfully control the symptoms and risks without harming the foetus. My view, developed by treating several patients at the Hammersmith Hospital in London, is that mothers (who have been fully alpha-blocked) should be taken to term, and delivered by caesarean section, without any attempt made to remove the tumour simultaneously.

Further radiological investigations, such as CT and MIBG scanning, can then be undertaken without risk to the baby, while the vascularity of the abdomen is allowed to settle over the next six to eight weeks. This gives the mother the opportunity to undergo laparoscopic resection of the phaeochromocytoma, rather than having to have an open procedure at the same time as the delivery.