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Most thyroid-stimulating hormone (TSH) assays now have the sensitivity required by thyroid guidelines and allow the reliable identification of patients with both overt and subclinical hyperthyroidism. Clinical guidelines usually quote decision limits for TSH, but often ignore the issue of whether variability in bias between assays should be considered when such decision limits are implemented. Clinicians and laboratories should appreciate that these decision limits arise largely from historical data that used TSH assays with poorly defined bias. It is thus unlikely that laboratories will be able to apply an appropriate method-related bias adjustment to these TSH cut-offs. Clinicians should appreciate that TSH decision limits should thus be regarded as typical target figures rather than an absolute cut-off and thus can be applied with some degree of flexibility. There is currently insufficient evidence to justify a significant lowering of the upper reference limit for TSH, but fine-tuning of current reference ranges is required since there appears to be no association between the ranking of the assay bias in the UK National External Quality Assessment Service scheme and the manufacturers? quoted reference ranges. There is room for further improvement in TSH assays and this can best be achieved if manufacturers, laboratories and clinicians work together to produce TSH assays and reference ranges that show closer agreement between methods. Until this is achieved, future studies that examine the relationship of TSH with symptoms and treatment should ensure that sufficient information is included in the publication to allow the method related bias of the TSH assay to be clearly described. [ABSTRACT FROM AUTHOR]

Background: As one of the most requested profiles of blood tests, there is a need for standardization among liver function tests (LFT). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are key markers of hepatocellular injury. ALT and AST are used to calculate a Fibrosis-4 (FIB-4) score for assessing liver fibrosis. Despite recommendations by the International Federation of Clinical Chemistry (IFCC) to include pyridoxal-5-phosphate in ALT and AST assay methodologies, most laboratories continue to omit this., Methods: Data from the UK NEQAS for Clinical Chemistry Scheme, Distribution 1160 (November 2023), was reviewed to investigate variation in practice regarding liver blood tests in relation to ALT, AST and FIB-4. In addition, a series of questions audited laboratory practice in relation to liver enzymes., Results: Wide variation was seen in LFT profiles offered by laboratories, with 32 different combinations of tests used. The IFCC-recommended methods for ALT and AST are used by one-third of laboratories and give significantly higher results than non-IFCC methods. Laboratories using IFCC methods also reported significantly higher FIB-4 scores. Reference ranges and cut-offs for these tests also varied, and did not account for method-related differences in results., Conclusions: The lack of standardization of LFTs can have a significant impact on patient care. The difference in results for ALT, AST and FIB-4 in laboratories not using IFCC-recommended methods may lead to misdiagnosis. This issue should be addressed by laboratories using methods including pyridoxal-5-phosphate. Until then, method-related reference ranges and cut-offs for ALT, AST and FIB-4 are required., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A sample received in the laboratory from a patient receiving total parenteral nutrition (TPN) indicated that the patient may have renal dysfunction, but the results were not considered to be reliable enough to report. Investigations using a reference method for measurement of creatinine confirmed positive interference in the creatinine assay and distribution of samples via an External Quality Assessment (EQA) Scheme showed that this positive interference was method dependent., Methods: Residual TPN fluid (Nutriflex Lipid Special) left in the bag after the patient had completed the infusion was collected and added to a patient serum pool in increasing amounts and distributed to different laboratories for analysis of creatinine and glucose through an EQA Scheme., Results: Positive interference in a number of different creatinine assays was identified as a result of a component in the TPN fluid. Positive interference from high concentrations of glucose has been demonstrated to be a cause for falsely high results in Jaffe creatinine assays., Conclusions: The concern would be that a sample contaminated with TPN fluid would have both abnormal electrolytes and creatinine concentrations and give the impression that the patient was in renal failure due to analytical interference in the creatinine assay and laboratory staff need to be aware of this problem., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: National Health Service England issued a Patient Safety Alert in 2014 mandating all acute Trusts in England to implement Acute Kidney Injury (AKI) warning stage results and to do so using a standardised algorithm. In 2021, the Renal and Pathology Getting It Right First Time (GIRFT) teams found significant variation in AKI reporting across the UK. A survey was designed to capture information on the entire AKI detection and alerting process to investigate the potential sources of this unwarranted variation., Methods: In August 2021, an online survey consisting of 54 questions was made available to all UK laboratories. The questions covered creatinine assays, laboratory information management systems (LIMS), the AKI algorithm and AKI reporting., Results: We received 101 responses from laboratories. Data were reviewed for England only - 91 laboratories. Findings included that 72% used enzymatic creatinine. In addition, 7 manufacturer-analytical platforms, 15 different LIMS and a wide range of creatinine reference ranges were in use. In 68% of laboratories, the AKI algorithm was installed by the LIMS provider. Marked variation was found in the minimum age of AKI reporting with only 18% starting at the recommended 1 month/28-days. Some 89% phoned all new AKI2s and AKI3s, as per AKI guidance while 76% provided comments/hyperlinks in reports., Conclusions: The national survey has identified laboratory practices that potentially contribute to unwarranted variation in the reporting of AKI in the England. This has formed the basis for improvement work to remedy the situation, including national recommendations, included within this article., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: UK Clinical laboratories have been routinely reporting an estimated glomerular filtration rate (eGFR) based on creatinine measurements using an eGFR equation since the early 2000s. Though there have been recommendations to use enzymatic based creatinine assays, and a recommendation of which equation to use, there still remains a high degree of variation in calculated eGFR results., Methods: Data from the UK NEQAS for Acute and Chronic Kidney Disease Scheme have been reviewed to look at the CKD equations that are currently in use in the UK and the impact on eGFR results reported. The UK NEQAS for Acute and Chronic Kidney Disease has over 400 participants measuring creatinine across all major clinical biochemistry platforms., Results: An audit of EQA registration against results returned showed that in February 2022 at most 44% of registered participants were correctly reporting the 2009 CKD-EPI equation. At higher creatinine concentrations (which give rise to lower eGFR results), the spread of eGFRs is tight and there is little difference between results from different method principles. However, at lower creatinine concentrations, where it is known that there is more variation in creatinine depending on method choice, both method principle and eGFR equation choice can influence calculated eGFR. In some cases, this can impact CKD Stage classification., Conclusions: CKD is a serious public health issue that requires accurate assessment of eGFR. Laboratories should be in constant dialogue with their renal teams about their creatinine assay performance and impact on eGFR reporting across their service., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilis eassay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems.

Background: This article describes three patients in whom measured serum testosterone concentrations were found to be artifactually high due to interference from norethisterone medication. This interference was investigated further by distributing samples containing norethisterone through an external quality assessment scheme., Methods: Serum samples containing different concentrations of norethisterone were distributed to participants in the UK external quality assessment scheme (UK NEQAS) for female testosterone in order to assess the degree of interference from norethisterone in different commercially available immunoassay and liquid chromatography-tandem mass spectrometry methods for measurement of testosterone., Results: The results have shown that apparent serum testosterone concentrations in excess of 5 nmol/L may be obtained using the Roche E170 Modular immunoassay method for samples collected from patients taking norethisterone medication and this interference can be reproduced by adding norethisterone to serum samples., Conclusions: Although the biggest interference is seen with the Roche system, there is a small effect in the Siemens ADVIA Centaur assay and some of the other immunoassays may also be affected to a much lesser extent. Norethisterone does not interfere in testosterone measurements obtained by liquid chromatography-tandem mass spectrometry.

Background: LC-MS/MS is rapidly becoming the technology of choice for measuring steroid hormones. We have developed a rapid LC-MS/MS assay for the routine analysis of serum cortisol. We have used this assay to investigate the effects of gender and exogenous steroid interference on the immunoassay measurement of serum cortisol., Methods: Zinc sulphate (40 µL) was added to 20 µL of sample. This was vortexed for 10 s followed by the addition of 100 µL of internal standard in methanol. Following mixing and centrifugation, 10 µL of sample was injected into an Acquity LC system coupled to a Quattro Premier tandem mass spectrometer. Serum samples (n = 149) were analysed by LC-MS/MS and two commercial immunoassays. Results were then compared for all samples and for gender differences. A further set of serum samples (n = 171) was analysed by the LC-MS/MS assay and a GC-MS assay., Results: Cortisol had a retention time of 0.98 min and the assay had an injection-to-injection time of 2.6 min per sample. Mean recovery was 99% and mean CV was 8%. The immunoassays gave comparisons of: Roche = 1.23 × LC-MS/MS -1.12 nmol/L and Abbott = 0.94 × LC-MS/MS + 11.97. The comparison with GC-MS showed LC-MS/MS = 1.11 × GC-MS - 22.90., Discussion: We have developed an LC-MS/MS assay for serum cortisol analysis that is suitable for routine clinical use and has been in use in our laboratory for 12 months. The availability of this assay will give more reliable results in patients receiving exogenous steroid therapy.

Proteinuria is a classic sign of kidney disease and its presence carries powerful prognostic information. Although proteinuria testing is enshrined in clinical practice guidelines, there is surprising variation among such guidelines as to the definition of clinically significant proteinuria. There is also poor agreement as to whether proteinuria should be defined in terms of albumin or total protein loss, with a different approach being used to stratify diabetic and non-diabetic nephropathy. Further, the role of reagent strip devices in the detection and assessment of proteinuria is unclear. This review explores these issues in relation to recent national and international guidelines on chronic kidney disease (CKD) and epidemiological evidence linking proteinuria and clinical outcome. The authors argue that use of urinary albumin measurement as the front-line test for proteinuria detection offers the best chance of improving the sensitivity, quality and consistency of approach to the early detection and management of CKD.

Background: Targets for cholesterol reduction are part of the Quality Outcomes Framework and general practitioners have to meet these targets to fulfil their remuneration package. By contrast, there are no targets for the accuracy of cholesterol or other lipid measurements and no recent surveys on performance of these assays. We have assessed the performance of lipid measurement of the available methods in the UK., Methods: Serum samples collected from individual donors attending the national blood service were distributed after values were obtained from a secondary reference laboratory. Samples were sent to participant laboratories to assess different methods' analytical performance on single donation specimens, on routine external quality assessment pooled specimens, on specimens subjected to a range of freeze-thaw cycles and on frozen-stored specimens., Results: Differences in measured cholesterol were found that were method-dependent and related to triglyceride content. HDL-cholesterol (HDL-C) showed significant positive bias in all assays. Individual donor specimens showed no significant changes with differing numbers of freeze-thaw cycles. Pooled serum was stable for up to six months., Conclusions: Most cholesterol measurements are accurate but some methods are affected by triglyceride interference. HDL-C methods show significant positive bias. Although there are potential matrix effects introduced as a result of specimen preparation, additional work is needed to show if these effects are present in fresh patient samples.