Contents
Introduction
Phaeochromocytoma is a tumour that produces catecholamines. Although it usually develops in the adrenal medulla, approximately 10% of cases arise in the sympathetic ganglia elsewhere. A wide range of ages can be affected but the bulk of cases occur between the ages of 40 to 60 years. The tumour is rare, having an incidence of 2-8 per 1000,000 per year.
Around 10% of cases are familial and can be seen in multiple endocrine neoplasia type 2, von Hippel Lindau syndrome, Sturge-Weber syndrome and neurofibromatosis. The familial cases usually occur at a younger age.
Pathology
Phaechromocytomas are benign in 90% of cases. Extra-adrenal primary tumours are more likely to be malignant.
Adrenal phaeochromocytomas are unilateral in 90% of patients. Their appearance can vary both in terms of size and colour. Some tumours are small whereas others can exceed 1kg in weight. The cut surface may be uniform or affected by haemorrhage and/or necrosis. The colour falls in the specrum of brown to red.
Microscopically the tumours are composed of nests or trabeculae of polyhedral cells which resemble those of the normal adrenal medulla. The nests of cells are known as zellballen. Sustentacular cells are retained.
As with parathyroid tumours the distinction between a benign and malignant phaeochromocytoma can be problematic. The existence of metastases remains a defining feature of malignancy but problems can arise in their absence, especially as invasion of the capsule can be found in benign tumours. Assorted features have been described to generate scoring systems that can predict whether or not the tumour will behave in a malignant fashion.
Metastases are to local lymph nodes then diverse targets.
The
cut up of phaeochromocytomas follows the basic pricinciples of the
cut up of a solid organ.
Phaechromocytomas are rather fond of the proportion 10%: they are familial in 10% of cases, bilateral in 10%, malignant in 10% and extra-adrenal in 10%.
Clinical Features
Phaeochromocytomas usually present with the consequences of the uncontrolled release of catecholamines by the tumour and thus tend to come to attention through their paraneoplastic phenomena rather than the direct effects of the mass itself.
The most common feature is hypertension (phaeochromocytomas account for 1 in 1000 cases of hypertension). The hypertension can be sustained or episodic. It can be of a sufficient degree to cause malignant hypertension (the term malignant is not employed in the neoplastic sense but instead with regard to the high morbidity and mortality the hypertension can cause).
Sweating and headaches are often encountered and their combination with hypertension is said to be suggestive of a phaeochromocytoma.
In addition to the the hypertension the effects on the cardiovascular system include tachycardia and tachyarrhythmias, which may present as palpitations. The overdrive imposed on the heart may be sufficient to provoke angina. A cardiomyopathy, either dilated or hypertrophic, can occur.
The catecholamines may induce vasoconstriction in the peripheries and thus Raynaud's phenomenon.
Anxiety may develop. This can reflect the effects of the catecholamines on the brain but may also be related to the cardiovascular effects: the feeling of anxiety is associated with the physical phenomena of tachycardia, palpitations and a dry mouth and by producing these physical features the phaeochromocytoma can yield physical responses that the brain interprets as anxiety.
The action of catecholamines on glucose metabolism can cause secondary diabetes mellitus.
Catecholamine crises occur in 50% of patients and are produced by a surge of release of catecholamines by anything that physically disturbs the tumour. Tachycardia, palpitations, severe hypertension, profuse sweating, anxiety, nausea and vomiting are the features.
Investigations
The mainstay of the diagnostic investigation of a phaeochromocytoma is to demonstrate the excess catecholamine secretion. This can be accomplished by measuring the quantity of catecholamines which are excreted in the urine over 24 hours. The urine can be tested for adrenaline and noradrenaline themselves and their breakdown product vanillylmandelic acid (which is also found in vanilla ice cream).
Blood levels of catecholamines can also be measured.
The blood glucose levels should be checked in order to evaluate the possibility of secondary diabetes mellitus. Other blood tests (FBC, U+E, LFT, calcium) are concerned more with the general work up of the clinical presentation and assessing the complications of the hypertension.
The adrenal glands are imaged with CT and/or MRI. Extra-adrenal tumours can be localised with nuclear medicine scans that use m-iodobenyzylguanidine (labelled with
123I).
Treatment
The main thrust of treatment is the surgical removal of the tumour. However, this must be preceded by treatment with an alpha-blocker, typically phenoxybenzamine. A beta-blocker can be added to control tachycardia and palpitations but alpha blockade must be established first; isolated beta blockade will mean that the actions of the catecholamines on blood vessels are restricted to vasoconstriction only and severe hypertension can occur.
The five year survival rate for benign tumours is 95% but for malignant tumours it is less than 50%.
Other Tumours
Given its derivation from cells of the neural crest the adrenal medulla is the location for some neuroblastomas and ganglioneuromas.