Is there still a place for pharmacological testing for phaeochromocytoma?

Phaeochromocytoma and extra-adrenal paragangliomas are rare catecholamine-producing tumours which, if not timely and properly diagnosed, may result in catastrophic consequences. 1 Definite exclusion or confirmation of the tumour is of utmost clinical importance. For this purpose several biochemical tests are available with those measuring metanephrines as the most accurate ones. Even at a very high prior test probability (for instance 75%), the test of plasma free metanephrines has negative and positive predictive values of nearly 95%. 2 In contrast, at a very low prior test probability of, for instance, 1%, the negative predictive value of plasma free metanephrines approaches 100% but the positive predictive value drops to 6%. Thus, both plasma and urinary metanephrines have a high sensitivity but a limited specificity and this means that they are fraught with a rate of false-positive test results of 20 to 30%, and less then 5% false-negative test results. 2 False-positive results are encountered in patients with slight increments of plasma metanephrines (<4 x the upper reference limit) or of urinary metanephrines (<2 x the upper reference limit) but no phaeochromocytoma. Several causes of false-positive test results such as medications and inappropriate sampling conditions can be dealt with appropriately. Another cause of a false-positive test result, which is more difficult to handle, is an increased secretion of catecholamines or metanephrines that is unrelated to phaeochromocytoma. This applies to several other clinical conditions that are associated with an increased secretion of catecholamines due to an increased sympathetic activity. Conversely, because of a rare false-negative test result, an occasional patient with a phaeochromocytoma may be missed with these tests. False-negative test results may occur in the event of a very small phaeochromocytoma or episodic catecholamine secretion by the tumour. In the last 60 years several pharmacological tests have been developed to unmask the presence of a phaeochro-mocytoma. These include glucagon, histamine and tyramine provocation tests, and clonidine and pentolinium suppression tests. The glucagon test and the clonidine test are the most widely used. Despite their use in several studies, abnormal responses of plasma catecholamines are not uniformly defined. Most papers traditionally rely only on the response of plasma norepinephrine levels for both glucagon and clonidine test. More importantly, normal responses of plasma catecholamines to these agents have hardly been assessed in healthy asymptomatic subjects. Finally, only a few small populations of mostly symptomatic patients, who appeared to have no phaeochro-mocytoma, have been studied as …