Rj Fitzgerald

The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested.

Reference Values for Urinary HMMA, HVA, Noradrenaline, Adrenaline, and Dopamine Excretion in Children Using Random Urine Samples and HPLC with Electrochemical Detection

Random urine samples were collected from 305 children aged from birth to 14 years and the values of hydroxymethoxymandelic acid, homovanillic acid, noradrenaline, adrenaline, and dopamine were measured by high-performance liquid chromatography with electrochemical detection. The results were reported relative to the urinary creatinine concentration and the values declined progressively with increasing age for each analyte with the exception of adrenaline. The results for each age group were not normally distributed and all values except outliers were retained in determining the upper reference limits.

Enzyme-linked immunoassay for plasma-free metanephrines in the biochemical diagnosis of phaeochromocytoma in adults is not ideal.

Abstract Background: The aim of the study was to define the analytical and diagnostic performance of the Labor Diagnostica Nord (LDN) 2-Met plasma ELISA assay for fractionated plasma metanephrines in the biochemical diagnosis of phaeochromocytoma. Methods: The stated manufacturer’s performance characteristics were assessed. Clinical utility was evaluated against liquid chromatography tandem mass spectrometry (LC-MS/MS) using bias, sensitivity and specificity outcomes. Samples (n=73) were collected from patients in whom phaeochromocytoma had been excluded (n=60) based on low probability of disease, repeat negative testing for urinary fractionated catecholamines and metanephrines, lack of radiological and histological evidence of a tumour and from a group (n=13) in whom the tumour had been histologically confirmed. Blood collected into k2EDTA tubes was processed within 30 min. Separated plasma was aliquoted (×2) and frozen at –40°C prior to analyses. One aliquot was analysed for plasma metanephrines using the LDN 2-Met ELISA and the other by LC-MS/MS. Results: The mean bias of –32% for normetanephrine (ELISA) when compared to the reference method (LC-MS/MS) makes under-diagnosis of phaeochromocytoma likely. The sensitivity of the assay (100%) was equal to the reference method, but specificity (88.3%) lower than the reference method (95%), making it less than optimum for the biochemical diagnosis of phaeochromocytoma. Conclusions: Plasma-free metanephrines as measured by Labor Diagnostica Nord (LDN) 2-Met ELISA do not display test characteristics that would support their introduction or continuation as part of a screening protocol for the biochemical detection of phaeochromocytoma unless the calibration problem identified is corrected and other more accurate and analytically specific methods remain unavailable.

Catecholamines in urine after death

Noradrenaline, adrenaline and dopamine levels were measured using high-performance liquid chromatography (HPLC) and electrochemical detection and related to urine creatinine in 30 specimens from unselected autopsies. Values calculated from patients with essential hypertension were used as a reference and raised values of noradrenaline, adrenaline and dopamine were found in 76.6, 80 and 23.3%, respectively. Using the Mann-Whitney U test, there was no difference between the 11 patients with myocardial infarction and the seven who died from severe head injury or multiple trauma. The median values in mmol/mol creatinine for patients with myocardial infarction and trauma were 0.07 and 0.12 for noradrenaline and 0.012 and 0.024 for adrenaline, respectively. Physiological stress is common before death and urine noradrenaline values at autopsy overlap those found in some normal subjects and at autopsy in patients with phaeochromocytoma.

Phaeochromocytoma — A laboratory experience

SummaryThirteen phaeochromocytomas were found over five and a half years from 2,834 patient requests for tumour screens. HMMA (VMA) was the usual screening test requested. Free catecholamines were reported when specifically requested by clinicians and where the HMMA level was >40 μmol/24 hr. HMMA and urinary free catecholamines were estimated using HPLC with electrochemical detection in acidified 24 hr collections. Noradrenaline was elevated in all thirteen, nine had raised adrenaline and two had raised levels of all three catecholamines. Urinary free catecholamines are the most appropriate analyte package in our circumstances for the diagnosis of phaeochromocytoma. HMMA if used alone could lead to false negative diagnoses but it has a role in minimising false negatives where urinary catecholamine results are normal.

Lack of uniformity in the clinical approach to the interpretation of urinary catecholamines and their metabolites

SummaryA study of the case notes from 101 of the 113 instances where at least one of the results was abnormal from the analysis of 24 hr urinary collections for noradrenaline, adrenaline, and dopamine and their metabolites 4-hydroxy-3-methoxy-mandelic acid (HMMA) and homovanillic acid (HVA) in screening for phaeochromocytomas in hospitals affiliated to the Royal College of Surgeons in Ireland Medical School from a total of 199 false positives from all sources shows that 51% had a second sample, 33% had ultra sound, 12% had a CT scan, 6% had an131I metaiodobenzylguanadine (MIBG) scan, 40% had no imaging performed and in 5% the reports were not received by the referring medical team. The 12 sets of data where case notes could not be retrieved were disregarded. Of the 22 patients with one or more biochemical value greater than twice the upper reference range, 8 had not, by our criteria had a phaeochromocytoma positively excluded. The sensitivity and specificity for phaeochromocytoma diagnosis for the free catecholamines together was 82% and 88.4%; for HMMA 60% and 95.8%; and for catecholamines and HMMA together 82% and 93.2% respectively. A protocol which includes repeat samples where results are abnormal and the appropriate use of diagnostic imaging should be systematically pursued to minimise false negative diagnoses.

An apparent phaeochromocytoma and abnormal thyroid function tests

Abstract A 41-year-old lady presented with classical symptoms of a phaeochromocytoma and markedly elevated urinary adrenaline concentration. Urinary fractionated metanephrine and normetanephrine concentrations were within the normal reference range. Computed tomography of the abdomen/pelvis and I123 meta-iodobenzylguanidine scans were negative. Factitious adrenaline use was established as the diagnosis.