Vitamin B12 reference intervals on Beckman, Roche and Siemens analytical platforms.

BACKGROUND: Vitamin B12 status is assessed primarily by measuring total serum B12 using competitive binding methods. The lack of availability of a standard material and high-level reference measurement procedure affect the trueness of B12 results; this results in variation between methods. This study aimed to determine the reference intervals for vitamin B12 on three routine analytical platforms. METHOD: A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. Vitamin B12 samples were measured on Roche, Beckman and Siemens analytical platforms. RESULTS: In total, 300 adult subjects were recruited; the central 95th centile values for B12 for Roche (190-678 ng/mL) and Siemens (181-562 ng/mL) analytical platforms were in a close agreement. Beckman DXi, however, showed a significantly lower reference limit (110-562 ng/mL). All reference intervals are in keeping with previously published data but some are not in agreement with manufacturer provided reference interval. CONCLUSION: As the quality of the reference intervals plays a significant role in clinical outcome, it is of great importance that laboratories use a method-specific reference interval and if possible, locally derived reference intervals until further method standardization occurs.

Comparison of method-related reference intervals for thyroid hormones: studies from a prospective reference population and a literature review.

Introduction Reference intervals are dependent on the reference population, the analytical methods and the way the data are handled statistically. Individual method-related differences have been studied but the comparative differences in reference intervals have not. Methods We studied a reference population of healthy adult subjects and measured free thyroxine and thyroid-stimulating hormone by the four most commonly used analytical platforms used in the UK. Subjects were excluded if they were > 65 years or had positive thyroid peroxidase antibodies. We also performed a systematic literature review of thyroid hormone reference interval studies in non-pregnant adults. Results In total, 303 subjects were recruited and 42 excluded. The central 95th centile values for thyroid-stimulating hormone (mIU/L) were Abbott Architect (0.51-3.67); Beckman Unicel DxI (0.57-3.60); Roche Cobas (0.60-4.31) and Siemens Advia Centaur XP (0.63-4.29). The 95th centile values for thyroxine (pmol/L) were Abbott Architect (10.6-15.5); Beckman Unicel DxI (7.9-13.0); Roche Cobas (12.5-19.6) and Siemens Advia Centaur XP (11.8-19.0). We identified 55 papers describing thyroid reference intervals in male and non-pregnant female adults. The values for upper and lower reference intervals by manufacturer varied but were not significantly different for thyroid-stimulating hormone but were for thyroxine. Discussion Our study demonstrates clearly that there are marked variations in the reference intervals for thyroid hormones between analytical platforms. There is an urgent need for standardization of thyroid hormone assays to permit transferability of results. Until then, guidelines will need to reflect this method-related difference.

Biological variation of cardiac troponin in stable haemodialysis patients.

BACKGROUND: Patients with end-stage renal failure exhibit a chronic elevation of serum cardiac troponin (cTn) concentration. In order to facilitate the diagnosis of myocardial infarction in these patients, it is necessary to distinguish an increased cTn concentration due to an acute event, from that being a manifestation of chronic elevation. The aim of this study was to gather biological variation data relating to two serum cTn assays, one, a hs-cTnT assay, the other a contemporary sensitive cTnI assay, among stable haemodialysis patients. It was hoped that this might inform as to the best way to use cTn assays to assist in the diagnosis of myocardial infarction in patients with end-stage renal failure. METHODS: Eighteen stable haemodialysis patients were recruited, of whom 16 completed the study. Predialysis blood samples were collected weekly for 10 weeks during the second dialysis session of the week. Analytical CV (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), reference change value (RCV) and index of individuality (II) were determined for both assays. RESULTS: All samples had a serum hs-cTnT concentration above the 99th percentile for a healthy population compared to 29.4% for cTnI. For hs-cTnT, the long-term CVA was 2.1%, CVI 10.5%, CVG 64.2%, RCV 28.1% and log-normal RCV (rise/fall) 34.4%/-25.6%. The corresponding values for cTnI were 7.1, 20.2, 100.5 and 79.8%/-44.4%. The II was 0.17 and 0.2 for hs-cTnT and cTnI, respectively. CONCLUSION: Long-term biological variation of cTn in stable haemodialysis patients is similar to that in healthy individuals and in patients with stable coronary arterial disease. The low II for cTnI and hs-cTnT in stable haemodialysis patients indicates that population-based decision points are of limited value. Serial measurements are required to detect significant changes in cTn concentrations and support diagnosis of myocardial infarction in these patients.

Persistently raised aspartate aminotransferase (AST) due to macro-AST in a rheumatology clinic.

Macrocomplexes between immunoglobins and aspartate aminotransferase (macro-AST) may result in persistently increased AST concentration. The presence of macro-AST in patients has been implicated in unnecessary investigations of abnormal liver function tests. We report the case of a 44-year-old female who presented to the rheumatology clinic with a 12-months' history of constant widespread pain affecting her limbs and was found to have an elevated AST concentration. Further information from her GP revealed a 14-years' history of elevated AST with otherwise normal liver function. Previous abdominal ultrasound and two liver biopsies carried out 2 years apart were normal. This prompted further analytical investigation by the biochemistry department which identified macro-AST as the cause. This case illustrates that persistently raised isolated AST concentration with no other abnormal indices may warrant macroenzyme analysis potentially avoiding unnecessary invasive investigations.

Hepatocellular carcinoma in variegate porphyria: a case report and literature review.

Variegate porphyria is an autosomal dominant acute hepatic porphyria characterized by photosensitivity and acute neurovisceral attacks. Hepatocellular carcinoma has been described as a potential complication of variegate porphyria in case reports. We report a case of a 48-year-old woman who was diagnosed with hepatocellular carcinoma following a brief history of right upper quadrant pain which was preceded by a few months of blistering lesions in sun-exposed areas. She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. Despite two hepatic resections, she developed pulmonary metastases. She responded remarkably well to Sorafenib and remains in remission 16 months after treatment. A review of the literature revealed that hepatocellular carcinoma in variegate porphyria has been described in at least eight cases. Retrospective and prospective cohort studies have suggested a plausible association between hepatocellular carcinoma and acute hepatic porphyrias. Hepatic porphyrias should be considered in the differential diagnoses of hepatocellular carcinoma of uncertain aetiology. Patients with known hepatic porphyrias may benefit from periodic monitoring for this complication.

Management of severe in-patient hyponatraemia: an audit in two teaching hospitals in Yorkshire, UK.

BACKGROUND: Hyponatraemia, the commonest electrolyte abnormality amongst in-patients, is associated with increased mortality. Until recently, there has been a lack of international consensus management of patients with severe hyponatraemia. AIM: We performed a retrospective study in two teaching hospitals in Yorkshire, UK, to evaluate the management of patients with severe hyponatraemia (serum Na ≤ 110 mmol/L) and to assess the frequency of complications observed in this group, in particular central pontine myelinolysis (CPM) and death. METHODS: Retrospective data collection was performed on all of patients admitted with severe hyponatraemia in a calendar year in two teaching hospitals in Yorkshire. A detailed case note evaluation was conducted to determine the patient clinical characteristics, aetiology, investigations performed, treatment, complications and outcome of patients. RESULTS: We identified 39 patients in total at both sites over a calendar year. There was a notable female predominance (n = 27), with the median (range) age being 65 (45-92) years and median sodium concentration 107 (94-110) mmol/L. Hyponatraemia was classified as acute (onset < 48 h) in six patients, chronic (onset > 48 h) in 20 patients and of unknown duration in 13 patients. Iatrogenic hyponatraemia secondary to drugs, especially thiazides was the most commonly observed aetiology. The mortality rate was 48.7% (n = 19) at the end of one year after admission episode and CPM was seen in 7.6% (n = 3) of patients. CONCLUSIONS: Severe hyponatraemia is associated with significant morbidity and mortality. Drug-induced hyponatraemia was the most common aetiology observed in our group of patients.

Rosuvastatin: a review of the pharmacology and clinical effectiveness in cardiovascular disease.

Rosuvastatin is a new generation HMG-CoA reductase inhibitor which exhibits some unique pharmacologic and pharmacokinetic properties. It has low extrahepatic tissue penetration, low potential for CYP3A4 interactions and substantial LDL-C lowering capacity and therefore has distinct advantages. We conducted a Medline literature search to identify rosuvastatin papers published in English. In this review, we outline the pharmacology of rosuvastatin, highlighting its efficacy and safety. We also review the major clinical trials with reference to primary and secondary prevention, familial hypercholesterolaemia and comparison with other statins. Finally we address its place in clinical practice.