Laboratory diagnosis of phaeochromocytoma: which analytes should we measure?
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 100% 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 mumol/24 h) of the non-tumour patients as the cut-off. By lowering the cut-off to 35 mumol/24 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.
Graham
P E
PE
Department of Chemical Pathology, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Smythe
G A
GA
Edwards
G A
GA
Lazarus
L
L
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000652:urine; D002395:Catecholamines / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000652:urine; D012680:Sensitivity and Specificity; D016482:Urinalysis / Q000379:methods*
D002395:Catecholamines