The details of six patients treated in the period April 1999 – October 2003 by members of the Section of Endocrine Surgery of the Royal Australasian College of Surgeons are outlined in Box 1. In all patients, clinical suspicion of phaeochromocytoma was raised by the presence of hypertension, paroxysmal symptoms, or both. Twenty-four-hour urinary catecholamine levels were found to be elevated, although in Patients 1–5 these abnormalities were confined to one or two analytes only. In all except Patient 2, adrenal lesions were discovered on imaging, with large haemorrhagic masses detected in patients with an acute presentation (Patients 5 and 6). Patients with abnormalities on computed tomography (CT) underwent surgery. In Patients 1, 3, and 4, the excised tissues were found to be pathologically normal or to show mild enlargement (benign). In Patients 5 and 6, blood clot and necrotic tissue comprised the bulk of the specimens (Box 2), with a phaeochromocytoma discovered in the latter patient. Of note, Patients 1–3 were receiving tricyclic antidepressants for non-standard uses that did not include the treatment of major depression.

False positive biochemical test results for phaeochromocytoma are common and present particular problems because of the low prevalence of the disease. The reported incidence of phaeochromocytoma is 2–8 per million people annually, accounting for less than 0.2% of all patients with hypertension.1 Despite the fact that phaeochromocytoma is a rare cause of hypertension, the diagnosis merits consideration in a potentially large group of patients for two reasons. Firstly, although the disease is frequently fatal if unrecognised, surgical removal is highly effective, achieving cure in greater than 90% of cases.2 Secondly, because no array of clinical indicators has proven to reliably include or exclude phaeochromocytoma,3 physicians must maintain a high level of suspicion and consider biochemical testing in patients at risk. The pretest probability for phaeochromocytoma is close to 0.5% (1 in 200 patients tested) in the presence of hypertension and suggestive symptoms.4 Assuming a specificity of 85% for biochemical testing, 30 false positive results are generated for every one patient with phaeochromocytoma identified.5

Fortunately, most false positive tests can be unmasked with careful additional investigation and/or the elimination of factors known to confound biochemical tests for levels of catecholamines and their metabolites.

The misleading elevations in urinary noradrenaline levels in Patients 1–3 can be ascribed to their taking tricyclic antidepressants. Medications and conditions that may result in raised levels of plasma and/or urine catecholamines and their metabolites, and result in false positive test results for phaeochromocytoma, are listed in Box 3. Among these drugs, tricyclic antidepressants and phenoxybenzamine have been the most frequently implicated, together accounting for more than 40% of medication-associated false positive results in a recent large study.6

In Patients 3 and 4, false positive biochemical findings led to the identification of small (1.5 cm) adrenal masses on CT scanning, both of which were found, on histopathological examination, to be benign. Clinically unapparent adrenal masses (“incidentalomas”) are found in 2.1% of subjects at autopsy and in 1%–4% of abdominal imaging studies. Most of these masses are benign, hormonally inactive tumours that do not require surgical management.7

Phaeochromocytomas presenting with acute haemorrhage at presentation have been reported previously,8,9 with haemorrhagic tumours often losing characteristic imaging appearances and functional markers. Tumour necrosis may initially result in massive catecholamine release, followed by failure to demonstrate excess catecholamine levels, as was seen in Patient 6. Mildly elevated urinary catecholamine levels may also be seen as a consequence of hyperadrenergia from an acute stress response at the time of haemorrhage into a non-phaeochromocytoma lesion, as occurred in Patient 5.

2 Computed tomography image of the haemorrhagic left adrenal mass in Patient 5