This tumour of chromaffin tissue, usually arising in the adrenal medulla, secretes principally noradrenaline, but also variable amounts of adrenaline. Symptoms are related to this. Hypertension may be sustained or intermittent. If the tumour secretes only noradrenaline, which stimulates a and Pj adrenoceptors, rises in blood pressure are accompanied by reflex bradycardia due to vagal activation; this is sufficient to overcome the chronotropic effect of p., receptor stimulation. The recognition of bradycardia at the time of catecholamine-induced symptoms (e.g. anxiety, termor or sweating) is useful in alerting the physician to the possibility of this rare syndrome, since physiological sympathetic nervous activation causes is coupled to vagal withdrawal, and causes tachycardia. If the tumour also secretes adrenaline, which stimulates a, p: and p2 adrenoceptors, blood pressure and heart rate change in parallel. This is because stimulation of the vasodilator P2 receptor in resistance arteries attenuates the rise in diastolic pressure, and vagal activation is insufficient then to oppose the chronotropic effect of combined pj and P2 receptor stimulation in the heart.
Diagnostic tests include measurement of catecholamine metabolites in urine followed by catecholamine concentrations in blood when the urine results are equivocal or high. With modern analytical techniques interference by drugs and diet is less troublesome than formerly.
Antihypertensive drugs may alter catecholamine concentrations (particularly those that induce a reflex increase in sympathetic activity, e.g. vasodilators). False-positive results in tests can then occur and in the past patients have undergone unnecessary operations.38
A variety of pharmacological tests is now available, and these are best performed in specialist units to avoid erroneous results, e.g. clonidine suppression test. Provocation tests are dangerous. A phaeochromocytoma may also be stimulated to secrete and cause a hypertensive attack by meto-clopramide and by any drug that releases histamine (opioids, curare, trimetaphan). The search for biochemical evidence for a phaeochromocytoma should always precede the radiological hunt for a tumour. The accurate measurement of adrenaline in plasma is itself invaluable in determining whether the tumour is likely to be adrenal or extra-adrenal for only adrenal tumours can synthesise adrenaline. This is because the enzyme which methylates noradrenaline to adrenaline needs to be induced by a concentration of Cortisol higher than that which normally circulates. Such a concentration is achieved within the normal adrenal gland by the porto-capillary circulation from cortex to medulla. The circulation is progressively disrupted as the tumour grows, so that very large adrenal tumours may cease to secrete adrenaline.
Control of blood pressure preoperatively or when the tumour cannot be removed is achieved by a-adrenoceptor blockade which reverses peripheral vasoconstriction. P-blockade may also be required to control tachycardia in patients with adrenaline-secreting tumours. Since adrenaline secretion, as explained above, tends to fall as tumours enlarge, tachycardia is not usually a major problem. Initiation of a-blocker treatment can unmask tachycardia, since there is no longer baroreceptor induced vagal
38 On the other hand, a positive test must not be ignored. In 1954, a hospital clinical chemistry laboratory was asked to set up a biological assay for catecholamines in the urine. The head of the laboratory tested urine from the lab staff to obtain a reference range for the assay. All were negative except his own which was strongly positive. He felt well and regarded the result as showing insufficient specificity of the test. Two years later a fluorometric assay became available. The urines of the lab staff were tested again with the same result. The head of the laboratory still felt well, but this time he decided to consult a physician colleague. A few days later, before the consultation, he was quietly reading a newspaper at home in the evening when he had a fatal cerebral infarction. Autopsy revealed a phaeochromocytoma. (Robinson R 1980 Tumours thatsecrete catecholamines. Wiley, Chichester.)
activation to oppose fS-receptor stimulation of the heart. A (3-receptor blocker should never be given alone, since abolition of the peripheral vasodilator effects of adrenaline leaves the powerful a effects unopposed. The injunction not to use a P-blocker in any patient with a suspected phaeochromocytoma can be circumvented by judicious use of low dose f3, selective blockade (e.g. bisoprolol 5 mg), which will not prevent adrenaline induced vasodilatation.
For phaeochromocytoma the preferred a blocker is not one of the selective oq blockers, as in essential hypertension, but the irreversible a-blocker, phen-oxybenzamine, whose blockade cannot be overcome by a catecholamine surge. Treatment should be for several weeks, if possible, prior to surgery, to allow the intravascular volume depletion, which is always present in phaeochromocytoma patients, to be reversed.
During surgical removal, phentolamine (or sodium nitroprusside) should be at hand to control rises in blood pressure when the tumour is handled. When the adrenal veins have been clamped, volume expansion is often required to maintain blood pressure even after adequate preoperative a-blockade. If a pressor infusion is still needed, isoprenaline is more use than the usual a-agonists, to which the patient will be insensitive due to existing a-receptor blockade.
Metirosine (a-methyltyrosine) has been used with some success to block catecholamine synthesis in malignant phaeochromocytomas.
Metaiodobenzylguanidine (MIBG, an analogue of guanethidine) is actively taken up by adrenergic tissue and is concentrated in phaeochromocytomas. Radioiodinated MIBG (123I-MIBG) allows localisation of tumours and detection of metastases; also selective therapeutic irradiation of functioning metastases or other tumours of chromaffin tissue, e.g. carcinoid.
Was this article helpful?
Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.