Diagnosis of Pheo / Para...

Biochemical diagnosis of pheochromocytomas and paragangliomas: A guide for patients

Graeme Eisenhofer PhD, Professor & Chief, Division of Clinical Neurochemistry, Institute of Clinical Chemistry & Laboratory Medicine and Department of Medicine, University Hospital Dresden, Dresden, Germany

What are pheochromocytomas and paragangliomas? Pheochromocytomas are tumors that arise from the adrenal glands, which sit atop each kidney. Paragangliomas are tumors that arise from similar cells, but at non-adrenal gland locations; they most commonly occur in the abdomen, but can also develop in the chest, head and neck. Both types of tumors are usually suspected because of effects produced by secretions of certain hormones, called catecholamines. Secretion of catecholamines by the tumors causes increases in blood pressure and a wide range of symptoms (e.g., headaches, sweatiness, palpitations, anxiety, panic attacks).

What are catecholamines? There are three catecholamines, the most well known of which is adrenaline (epinephrine) formed almost entirely in the adrenal glands. The other catecholamines include noradrenaline (norepinephrine) and dopamine. Noradrenaline is secreted mainly by nerves that go to the blood vessels, heart and other organs. Noradrenaline is also formed in the adrenal glands where it is converted to adrenaline. Dopamine is the building block catecholamine from which noradrenaline is formed.

Which catecholamines are formed by what tumors? The three catecholamines are formed within tumors in different amounts depending on tumor type. About a half of all pheochromocytomas produce both adrenaline and noradrenaline in various proportions, while the other half produce only noradrenaline. In contrast, most paragangliomas secrete only noradrenaline, but others produce both dopamine and noradrenaline in varying amounts, including some that produce only dopamine. Other paragangliomas, particularly those of the head and neck, produce no catecholamines.

Which catecholamines cause what effects? It is only the tumors that produce adrenaline, noradrenaline or both catecholamines that cause increases in blood pressure and symptoms such as headaches, sweatiness, and palpitations. Tumors that produce only dopamine, as well those that produce no catecholamines, do not cause high blood pressure or the usual symptoms. However, some tumors that produce adrenaline or noradrenaline do not secrete the hormones in large enough amounts to produce increases in blood pressure or symptoms of catecholamine excess. Such tumors and tumors that produce only dopamine are usually found for other reasons.

What biochemical tests are used for diagnosis of pheochromocytomas and paragangliomas? Biochemical tests used for diagnosis of pheochromocytomas and paragangliomas include measurements in blood or urine of the catecholamines and various breakdown products (metabolites) of the catecholamines. The metabolites most commonly measured include normetanephrine, the breakdown product of noradrenaline, and metanephrine, the breakdown product of adrenaline. These two metabolites, normetanephrine and metanephrine, are commonly referred to in the plural form as the “metanephrines”. It is incorrect to refer to these metabolites in their single form as “normetanephrines” and “metanephrines”. In addition to normetanephrine and metanephrine, some laboratories also measure methoxytyramine, which is the breakdown product of dopamine. Another biochemical test still offered by some laboratories involves measurements in urine of vanillymandelic acid (commonly referred to as VMA), which represents the final major breakdown product of both noradrenalne and adrenaline. Measurements of plasma chromogranin A (CgA) are another test sometimes used to diagnose pheochromocytomas and paragangliomas. Chromogranin A is not a catecholamine or a catecholamine metabolite, but is secreted by the same cells that secrete catecholamines.

What biochemical tests are recommended for diagnosis of pheochromocytomas and paragangliomas? It is recommended that initial testing for pheochromocytomas and paragangliomas always include measurements of either or both urine or blood levels of metanephrines.