SUMMARY. There is a diversity of advice in the literature as to which biochemical assays are best suited to the investigation of patients with a suspected phaeochromocytoma. The challenge for the clinical laboratory is to select those assays which detect all phaeochromocytomas, whilst having the lowest incidence of false positive diagnoses. We compared the sensitivity and specificity of a wide range of assays currently used for the biochemical diagnosis of phaeochromocytoma using either specific gas chromatographic-mass spectrometric (GC/MS) or high performance liquid chromatography-electrochemical detection (HPLC/ED) techniques.Noradrenaline (NA), adrenaline (ADR), dopamine (DA), 3,4-dihydroxyphenylglycol (DHPG), hydroxymethoxymandelic acid (HMMA), normetanephrine (NMET) and metanephrine (MET) were measured in 24 h urine specimens from 20 patients with histologically proven phaeochromocytoma and a large group of patients referred for investigation but subsequently found not to have a phaeochromocytoma. Because phaeochromocytomas are a heterogeneous group of hormone secreting tumours, no single analyte could achieve 100D,10 sensitivity; 100% sensitivity was achieved only when the combination of both NA and ADR or NMET and MET was used. DA, DHPG and HMMA all had poor sensitivities. HMMA had a sensitivity of 70% when using the upper 95% confidence level (48 p.mol/24 h) of the non-tumour patients as the cut-off. By lowering the cut-off to 35 p.mo1124 h the sensitivity could be increased to 100% but at the expense of the specificity which was decreased from 98 to 92%. On the basis of this study we recommend the specific measurement of either NA and ADR or NMET and MET as the most suitable analytes for the detection of phaeochromocytoma, and further that, due to its poor specificity, HMMA be abandoned as a suitable analyte.
Additional key phrases: catecholamines; metanephrines; gas chromatography-mass spectrometry; high performance liquid chromatographyDespite recent advances in imaging technology, quantitative determinations of catecholamines and their metabolites remain the main diagnostic tool for the detection of phaeochromocytorna."? As a missed diagnosis may lead to a fatal outcome, it is vital that the screening test performed by the laboratory is the best available. We have previously reported that phaeochromocytomas are a heterogeneous group of tumours with a variety of excretion patterns and that laboratories screening for phaeochromocytoma must measure appropriate analytes able to encompass the full spectrum of Correspondence: Mr P E Graham. hormone production.4.~To date, various studies have differed as to which tests are superior and should be recommended for screening.t-"The need to use appropriate technology is highlighted by poor performance in Australian quality assurance surveys by a significant number of laboratories which are still using outmoded spectrophotometric assays based on the Pisano technique for the measurement of catecholamine metabolites." Similar surveys in the United Kingdom show tha...