Melanie J Griffiths

B-type natriuretic peptide in reversible myocardial ischaemia

Background: Coronary heart disease is associated with increased B-type natriuretic peptides (BNPs), and, although controversial, may cause exaggerated exercise-induced BNP secretion. We investigated BNP in relation to reversible myocardial ischaemia. Materials and methods: Serum N-terminal proBNP (NT-proBNP) was measured before and after an exercise electrocardiogram test (ETT) in 14 patients with and 45 patients without exercise-induced myocardial ischaemia. Statistical analysis was carried out on logarithmically transformed data. Results, however, are pre-transformed data. Results: NT-proBNP increased with exercise both in ETT-positive patients (mean (SD) 71.4 (41.2) v 76.8 (44.0) ng/l; p<0.001) and ETT-negative patients (54.0 (61.2) v 60.1 (69.0) ng/l; p<0.001). Pre-exercise and post-exercise NT-proBNP were higher (p<0.05) in ETT-positive than in ETT-negative patients. Incremental NT-proBNP was similar in ETT-positive (4.7 (4.2) ng/l) and ETT-negative (6.2 (8.6) ng/l) patients. Conclusion: Serum NT-proBNP concentrations are higher in patients with exercise-induced myocardial ischaemia than in those without. Exercise-induced electrocardiographic myocardial ischaemia, however, is not associated with exaggerated BNP secretion.

Revised national guidelines for the analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage: interpret with caution

We wish to add a cautionary note regarding removal of the correction for serum bilirubin in the presence of increased cerebrospinal fluid (CSF) bilirubin and oxyhaemoglobin from the revised national guidelines for the analysis of CSF for bilirubin in suspected subarachnoid haemorrhage (SAH).1 Recently we received a CSF sample requesting “xanthochromia” from a patient who had a normal CT brain scan. On CSF spectroscopy, both oxyhaemoglobin and bilirubin peaks were clearly visible. The net oxyhaemoglobin (OxyHb) and bilirubin absorbance were 0.0205 AU and 0.0146 AU, respectively. Under the revised guidelines1 this would have been unequivocally but erroneously reported as “Bilirubin and oxyhaemoglobin increased. …

Comparison of original (2003) and revised (2008) national guidelines for reporting of cerebrospinal fluid spectrophotometric scanning for suspected subarachnoid haemorrhage against patient outcome

Background National guidelines for cerebrospinal fluid (CSF) analysis and its reporting in suspected subarachnoid haemorrhage (SAH) were published in 2003, but revised in 2008 to give greater clarity in interpretation. It is not known whether the less ambiguous reporting of 2008 guidelines may lead to a false assurance and adversely affect patient outcome. We, therefore, re-interpreted scans reported under the 2003 guidelines, using the 2008 guidelines and compared these reports against final diagnosis and patient outcome obtained from a retrospective case-note review audit. Methods We identified requests for CSF xanthochromia studies from the laboratory system between September 2006 and August 2007. Spectroscopy scans were then retrieved and re-interpreted using the 2008 guidelines. The original reports and re-interpreted scans were compared against diagnosis and patient outcome using case-note review. Results We received 93 requests for CSF spectroscopy on 90 patients. Fourteen requests were not processed due to insufficient sample, but of these three patients had a repeat lumbar puncture (LP). Two further requests were not processed at the request of the clinician as they were no longer clinically indicated. Therefore, 77 spectroscopic scans were re-interpreted. The revised guidelines re-classified 11 previously equivocal scans into the not supportive of SAH category. On case-note review, one patient had a subsequent fatal SAH. The remaining 10 were given non-SAH final diagnoses and none had similar further inpatient episodes for at least 12 months and up to 18 months following LP. Conclusions The revised (2008) national guidelines for the analysis of CSF in suspected SAH offer greater clarity in reporting without adversely affecting patient outcome.

NT-proBNP and exercise.

Penney’s excellent review on natriuretic peptides lists exercise prior to sampling as a potential cause for a false-positive brain natriuretic peptide (BNP) in relation to chronic heart failure (CHF). This, however, is based on studies reporting a percentage rather than a more relevant absolute increase in BNP after exercise in healthy young men and marathon runners. We studied serum N-terminal pro-brain natriuretic peptide (NT-proBNP) (Elecsys proBNP, Roche Diagnostics GmbH, Mannheim, Germany) during an exercise electrocardiogram test in a more representative group of 64 patients without CHF (34 women and 30 men aged 56.5713.5 years [mean7SD]). Subjects exercised for 7.073.3min to an intensity of 8.473.3 Metabolic Equivalents. Serum NT-proBNP, 15min after exercise, was higher than at rest (59.3752.9 and 54.0747.8 ng/L, respectively; Po0.0001 [paired t-test]). The absolute and percentage increases in NT-proBNP after exercise were 5.176.2 ng/L and 11.279.2%, respectively. In all subjects, post-exercise serum NT-proBNP concentrations remained within ageand gender-derived reference ranges. McNairy et al. reported that exercise increases BNP by 55%, 30% and 19% in controls, patients with mild CHFand patients with moderate to severe CHF, respectively. Of greater relevance, however, they similarly reported that post-exercise BNP values in control subjects were within the reference range. Subjects presenting with dyspnoea are likely to have reduced exercise capacity. Pragmatically, therefore, exercise is unlikely to cause false-positive BNP or NTproBNP results in patients being investigated for CHF.

Recurrent dizzy spells: all in the head.

We read with interest the case report of McAulay et al., who reported spontaneous hypoinsulinaemic hypoglycaemia due to proposed counter-regulatoryhormone de¢ciencies as a result of previous bilateral adrenalectomy and pituitary radiotherapy following unsuccessful transphenoidal surgery for Cushing’s disease. Although less likely, McAulay et al. should have considered and excluded an alternative and more common diagnosis to explain the reported clinical and biochemical features, namely non-islet cell tumour hypoglycaemia (NICTH). NICTH is most commonly caused by tumours, whichmaybe small and occult, secretingabnormal insulin-like growth factor (IGF)-II, also called big IGF. The insulin-like activityof IGF-II leads tohypoglycaemiawith consequent suppression of pancreatic B-cell secretion, lipolysis and ketogenesis. Feedback of IGF-II on the hypothalamic-pituitary axis suppresses growth hormone (GH) with subsequent lowering of GH-dependent IGF-Iand IGF-binding proteins secreted by the liver. Tumours secreting IGF-II are, therefore, characterized by hypoglycaemiawith suppressed insulin and C-peptide, and inappropriately low GH (as in this case), but also an increased total IGF-II:IGF-I ratio and inappropriately low ketone levels. In addition, hypoglycaemia due to NICTH may respond to treatment with GH. Thus, NICTH could explainall the clinical and biochemical features reported, including the favourable response to GH treatment. Measurement of plasma ketones and IGF-II:IGF-I ratio would have di¡erentiated between hypoinsulinaemic hypoglycaemia due to NICTH (low ketones, high ratio) and counter-regulatory hormone de¢ciencies (high ketones, normal ratio). We suggest that it is particularly important to exclude NICTH as its long-term prognosis is likely to be less favourable than that of the proposed iatrogenic counter-regulatory hormone de¢ciencies. In the same issue, Murphy and colleagues discuss the potential value of re£ective testing. This case provides an example where re£ex or re£ective testing would have led to more appropriate biochemical investigation and may have even prevented unnecessary investigation, such as the predictably normal pancreatic imaging studies.

The sweat test: effect of elution time on chloride and sodium concentrations

Background: The National Committee for Clinical Laboratory Standards guidelines and Guidelines for the Performance of the Sweat Test for the Diagnosis of Cystic Fibrosis in the United Kingdom recommend that sweat be eluted from filter paper for a minimum of 40 min. In the absence of published data, this recommendation is based on expert opinion. We therefore investigated the effect of elution time on chloride and sodium concentrations. Methods: The effect of elution time (up to three hours) on chloride and sodium concentrations was studied as recommended for measurement of quality control samples using external quality assessment solutions. Results: There were no significant differences in eluted chloride and sodium concentrations with time of elution up to 3 h. Conclusion: Elution time within 3 h had no effect on chloride and sodium concentrations when eluted from filter paper.

Testicular germ cell tumour presenting as thyrotoxicosis.

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